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American Society of Clinical Oncology (ASCO): Annual Meeting
TEXT/SOFT provide practice-changing results for premenopausal breast cancer
CHICAGO – Adjuvant exemestane is more effective at preventing recurrence than tamoxifen is when either is given with ovarian function suppression in premenopausal women with hormone-sensitive breast cancers, according to a joint analysis of the phase III TEXT and SOFT trials.
"Exemestane plus OFS [ovarian function suppression] significantly improves disease-free survival, breast cancer free–interval, and distant recurrence free–interval and is a new treatment option for premenopausal women with hormone receptor-positive early breast cancer," lead study author Dr. Olivia Pagani said during a plenary session at the annual meeting of the American Society of Clinical Oncology.
The results were consistent in TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial), and in women who did and did not receive chemotherapy, said Dr. Pagani, clinical director of the breast unit at the Oncology Institute of Southern Switzerland, Bellinzona.
Among the 43% of women who did not receive chemotherapy, 97.6% of these women in TEXT and 97.5% in SOFT who received the aromatase inhibitor exemestane (Aromasin) remained free from breast cancer at 5 years.
On average, these women had lower-risk features such as older age and smaller tumors, however, 21% of them in TEXT and 8% in SOFT had node-positive disease, she observed. After 5.7 years median follow-up, there were very few distant recurrences in this subgroup, only 1% in the exemestane group.
"These results suggest that some premenopausal women have an excellent prognosis with highly effective endocrine therapy without chemotherapy," Dr. Pagani said.
Invited discussant Dr. Nancy E. Davidson, director of the University of Pittsburgh Cancer Institute, said, "We should remember the power of endocrine therapy in properly selected patients of all ages. Not every premenopausal patient needs chemotherapy."
Dr. Davidson said the results show that the combination of ovarian suppression and an aromatase inhibitor (AI) is "an evidence-based approach and may provide support to use the combination in women who cannot take tamoxifen or perhaps in those at very high risk, especially if they don’t take chemotherapy."
She went on to say, however, that "For now, I’m waiting for the results of SOFT to finalize my approach."
Currently, the standard adjuvant endocrine therapy for premenopausal women is 5 years of tamoxifen, while aromatase inhibitors are primarily used in postmenopausal women, where they have been shown to improve outcomes over tamoxifen.
Physicians in some countries, typically outside the United States, however, recommend adding OFS to tamoxifen in high-risk younger women, but the benefit of this strategy is uncertain. SOFT included a third treatment arm of tamoxifen alone to address the role of OFS for women receiving tamoxifen, but those results are not expected until late 2014.
Study details
The joint analysis, simultaneously published online in the New England Journal of Medicine, included 4,690 premenopausal women with early hormone-sensitive breast cancer, who were randomly assigned to exemestane 25 mg daily or tamoxifen 20 mg daily for 5 years (2014 [doi:10.1056/NEJMoa1404037]).
Randomization occurred within 12 weeks of surgery for all women in TEXT and women in SOFT who did not receive chemotherapy. Women in SOFT who received prior (neo)adjuvant chemotherapy were randomized within 8 months of chemotherapy completion when premenopausal status was demonstrated.
OFS in both trials was achieved through monthly injections of the gonadotropin-releasing hormone agonist triptorelin pamoate (Trelstar Depot), bilateral oophorectomy, or ovarian radiation.
Routine use of bisphosphonates was not permitted, but adjuvant trastuzumab was allowed, if indicated.
Overall, 42% of women were lymph node–positive, 36% had tumors larger than 2 cm, and 12% had human epidermal growth factor receptor 2–positive breast cancer. Their median age was 43 years.
Outcomes
At 5 years, exemestane plus OFS significantly improved the primary endpoint of disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (hazard ratio, 0.72; P = .0002), Dr. Pagani said.
No striking heterogeneity of treatment effect was observed in prospectively planned subgroup analyses including the cohorts defined by trial, chemotherapy stratum, and node status.
"The relative and absolute differences at 5 years compare favorably with those reported in the practice-changing BIG 1-98 and ATAC [Arimidex, Tamoxifen, Alone or in Combination] trials of aromatase inhibitors vs. tamoxifen in postmenopausal women," she said.
At 5 years, 92.8% of women assigned to receive exemestane plus ovarian suppression were free from breast cancer vs. 88.8% of those given tamoxifen plus ovarian suppression (HR, 0.66; P less than .0001).
The rate of freedom from distant recurrence at 5 years was also superior in the exemestane group (93.8% vs. 92%; HR, 0.78; P = .02). In all, 60% of first events involved distant sites.
These benefits, however, have yet to translate into a significant overall survival benefit at 5 years for exemestane plus ovarian suppression, compared with tamoxifen plus ovarian suppression (95.9% vs. 96.9%; HR, 1.14; P = .37), said Dr. Pagani, who added that conclusions about long-term survival are premature at this early follow-up.
Where do we go from here?
ASCO immediate past-president Dr. Clifford Hudis said in a press briefing that the joint analysis provides long-awaited and actionable information on how best to treat premenopausal women with hormone-sensitive breast cancer who appear cured after surgery, but that data from the tamoxifen-alone arm in SOFT are needed to change practice for those unconvinced about the need for ovarian suppression.
Dr. Davidson said she’s left pondering how the results will be integrated into practice. Will clinicians use 10 years of tamoxifen, as supported by the ATLAS and aTTOM trials, or will they use an extended adjuvant approach of 5 years of tamoxifen followed by a switch to 5 years of AI for women who become postmenopausal during their tamoxifen, as supported by the MA 17 trial? It’s also possible some will follow the lead set by TEXT/SOFT and use 5 years of ovarian suppression and AI.
"If the benefits of OFS with AI hold up, we may want to revisit the role of oophorectomy in selected patients, who want to avoid injections and have a permanent menopause," she added. "We will need to make sure we maximize bisphosphonates for bone health, but I’m not prepared to use bisphosphonates as a routine form of adjuvant therapy in these women just yet."
Finally, Dr. Davidson said long-term follow-up of TEXT/SOFT is vital for both benefit and toxicity. Though overall compliance was good, she noted earlier in her talk that 16% of women on exemestane plus OFS prematurely stopped therapy vs. 11% on tamoxifen plus OFS. "Financial toxicity" is also an issue, with the wholesale acquisition cost at her institution for 1 year of exemestane 25 mg daily at $7,344 vs. $1,369 for tamoxifen, she said.
Dr. Pagani stressed during the press briefing that the results do not mean all premenopausal women should be given an AI plus ovarian suppression, but that the decision should be individualized with input from the physician and patient.
The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute (NCI). Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and National Institutes of Health (NIH).
CHICAGO – Adjuvant exemestane is more effective at preventing recurrence than tamoxifen is when either is given with ovarian function suppression in premenopausal women with hormone-sensitive breast cancers, according to a joint analysis of the phase III TEXT and SOFT trials.
"Exemestane plus OFS [ovarian function suppression] significantly improves disease-free survival, breast cancer free–interval, and distant recurrence free–interval and is a new treatment option for premenopausal women with hormone receptor-positive early breast cancer," lead study author Dr. Olivia Pagani said during a plenary session at the annual meeting of the American Society of Clinical Oncology.
The results were consistent in TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial), and in women who did and did not receive chemotherapy, said Dr. Pagani, clinical director of the breast unit at the Oncology Institute of Southern Switzerland, Bellinzona.
Among the 43% of women who did not receive chemotherapy, 97.6% of these women in TEXT and 97.5% in SOFT who received the aromatase inhibitor exemestane (Aromasin) remained free from breast cancer at 5 years.
On average, these women had lower-risk features such as older age and smaller tumors, however, 21% of them in TEXT and 8% in SOFT had node-positive disease, she observed. After 5.7 years median follow-up, there were very few distant recurrences in this subgroup, only 1% in the exemestane group.
"These results suggest that some premenopausal women have an excellent prognosis with highly effective endocrine therapy without chemotherapy," Dr. Pagani said.
Invited discussant Dr. Nancy E. Davidson, director of the University of Pittsburgh Cancer Institute, said, "We should remember the power of endocrine therapy in properly selected patients of all ages. Not every premenopausal patient needs chemotherapy."
Dr. Davidson said the results show that the combination of ovarian suppression and an aromatase inhibitor (AI) is "an evidence-based approach and may provide support to use the combination in women who cannot take tamoxifen or perhaps in those at very high risk, especially if they don’t take chemotherapy."
She went on to say, however, that "For now, I’m waiting for the results of SOFT to finalize my approach."
Currently, the standard adjuvant endocrine therapy for premenopausal women is 5 years of tamoxifen, while aromatase inhibitors are primarily used in postmenopausal women, where they have been shown to improve outcomes over tamoxifen.
Physicians in some countries, typically outside the United States, however, recommend adding OFS to tamoxifen in high-risk younger women, but the benefit of this strategy is uncertain. SOFT included a third treatment arm of tamoxifen alone to address the role of OFS for women receiving tamoxifen, but those results are not expected until late 2014.
Study details
The joint analysis, simultaneously published online in the New England Journal of Medicine, included 4,690 premenopausal women with early hormone-sensitive breast cancer, who were randomly assigned to exemestane 25 mg daily or tamoxifen 20 mg daily for 5 years (2014 [doi:10.1056/NEJMoa1404037]).
Randomization occurred within 12 weeks of surgery for all women in TEXT and women in SOFT who did not receive chemotherapy. Women in SOFT who received prior (neo)adjuvant chemotherapy were randomized within 8 months of chemotherapy completion when premenopausal status was demonstrated.
OFS in both trials was achieved through monthly injections of the gonadotropin-releasing hormone agonist triptorelin pamoate (Trelstar Depot), bilateral oophorectomy, or ovarian radiation.
Routine use of bisphosphonates was not permitted, but adjuvant trastuzumab was allowed, if indicated.
Overall, 42% of women were lymph node–positive, 36% had tumors larger than 2 cm, and 12% had human epidermal growth factor receptor 2–positive breast cancer. Their median age was 43 years.
Outcomes
At 5 years, exemestane plus OFS significantly improved the primary endpoint of disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (hazard ratio, 0.72; P = .0002), Dr. Pagani said.
No striking heterogeneity of treatment effect was observed in prospectively planned subgroup analyses including the cohorts defined by trial, chemotherapy stratum, and node status.
"The relative and absolute differences at 5 years compare favorably with those reported in the practice-changing BIG 1-98 and ATAC [Arimidex, Tamoxifen, Alone or in Combination] trials of aromatase inhibitors vs. tamoxifen in postmenopausal women," she said.
At 5 years, 92.8% of women assigned to receive exemestane plus ovarian suppression were free from breast cancer vs. 88.8% of those given tamoxifen plus ovarian suppression (HR, 0.66; P less than .0001).
The rate of freedom from distant recurrence at 5 years was also superior in the exemestane group (93.8% vs. 92%; HR, 0.78; P = .02). In all, 60% of first events involved distant sites.
These benefits, however, have yet to translate into a significant overall survival benefit at 5 years for exemestane plus ovarian suppression, compared with tamoxifen plus ovarian suppression (95.9% vs. 96.9%; HR, 1.14; P = .37), said Dr. Pagani, who added that conclusions about long-term survival are premature at this early follow-up.
Where do we go from here?
ASCO immediate past-president Dr. Clifford Hudis said in a press briefing that the joint analysis provides long-awaited and actionable information on how best to treat premenopausal women with hormone-sensitive breast cancer who appear cured after surgery, but that data from the tamoxifen-alone arm in SOFT are needed to change practice for those unconvinced about the need for ovarian suppression.
Dr. Davidson said she’s left pondering how the results will be integrated into practice. Will clinicians use 10 years of tamoxifen, as supported by the ATLAS and aTTOM trials, or will they use an extended adjuvant approach of 5 years of tamoxifen followed by a switch to 5 years of AI for women who become postmenopausal during their tamoxifen, as supported by the MA 17 trial? It’s also possible some will follow the lead set by TEXT/SOFT and use 5 years of ovarian suppression and AI.
"If the benefits of OFS with AI hold up, we may want to revisit the role of oophorectomy in selected patients, who want to avoid injections and have a permanent menopause," she added. "We will need to make sure we maximize bisphosphonates for bone health, but I’m not prepared to use bisphosphonates as a routine form of adjuvant therapy in these women just yet."
Finally, Dr. Davidson said long-term follow-up of TEXT/SOFT is vital for both benefit and toxicity. Though overall compliance was good, she noted earlier in her talk that 16% of women on exemestane plus OFS prematurely stopped therapy vs. 11% on tamoxifen plus OFS. "Financial toxicity" is also an issue, with the wholesale acquisition cost at her institution for 1 year of exemestane 25 mg daily at $7,344 vs. $1,369 for tamoxifen, she said.
Dr. Pagani stressed during the press briefing that the results do not mean all premenopausal women should be given an AI plus ovarian suppression, but that the decision should be individualized with input from the physician and patient.
The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute (NCI). Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and National Institutes of Health (NIH).
CHICAGO – Adjuvant exemestane is more effective at preventing recurrence than tamoxifen is when either is given with ovarian function suppression in premenopausal women with hormone-sensitive breast cancers, according to a joint analysis of the phase III TEXT and SOFT trials.
"Exemestane plus OFS [ovarian function suppression] significantly improves disease-free survival, breast cancer free–interval, and distant recurrence free–interval and is a new treatment option for premenopausal women with hormone receptor-positive early breast cancer," lead study author Dr. Olivia Pagani said during a plenary session at the annual meeting of the American Society of Clinical Oncology.
The results were consistent in TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial), and in women who did and did not receive chemotherapy, said Dr. Pagani, clinical director of the breast unit at the Oncology Institute of Southern Switzerland, Bellinzona.
Among the 43% of women who did not receive chemotherapy, 97.6% of these women in TEXT and 97.5% in SOFT who received the aromatase inhibitor exemestane (Aromasin) remained free from breast cancer at 5 years.
On average, these women had lower-risk features such as older age and smaller tumors, however, 21% of them in TEXT and 8% in SOFT had node-positive disease, she observed. After 5.7 years median follow-up, there were very few distant recurrences in this subgroup, only 1% in the exemestane group.
"These results suggest that some premenopausal women have an excellent prognosis with highly effective endocrine therapy without chemotherapy," Dr. Pagani said.
Invited discussant Dr. Nancy E. Davidson, director of the University of Pittsburgh Cancer Institute, said, "We should remember the power of endocrine therapy in properly selected patients of all ages. Not every premenopausal patient needs chemotherapy."
Dr. Davidson said the results show that the combination of ovarian suppression and an aromatase inhibitor (AI) is "an evidence-based approach and may provide support to use the combination in women who cannot take tamoxifen or perhaps in those at very high risk, especially if they don’t take chemotherapy."
She went on to say, however, that "For now, I’m waiting for the results of SOFT to finalize my approach."
Currently, the standard adjuvant endocrine therapy for premenopausal women is 5 years of tamoxifen, while aromatase inhibitors are primarily used in postmenopausal women, where they have been shown to improve outcomes over tamoxifen.
Physicians in some countries, typically outside the United States, however, recommend adding OFS to tamoxifen in high-risk younger women, but the benefit of this strategy is uncertain. SOFT included a third treatment arm of tamoxifen alone to address the role of OFS for women receiving tamoxifen, but those results are not expected until late 2014.
Study details
The joint analysis, simultaneously published online in the New England Journal of Medicine, included 4,690 premenopausal women with early hormone-sensitive breast cancer, who were randomly assigned to exemestane 25 mg daily or tamoxifen 20 mg daily for 5 years (2014 [doi:10.1056/NEJMoa1404037]).
Randomization occurred within 12 weeks of surgery for all women in TEXT and women in SOFT who did not receive chemotherapy. Women in SOFT who received prior (neo)adjuvant chemotherapy were randomized within 8 months of chemotherapy completion when premenopausal status was demonstrated.
OFS in both trials was achieved through monthly injections of the gonadotropin-releasing hormone agonist triptorelin pamoate (Trelstar Depot), bilateral oophorectomy, or ovarian radiation.
Routine use of bisphosphonates was not permitted, but adjuvant trastuzumab was allowed, if indicated.
Overall, 42% of women were lymph node–positive, 36% had tumors larger than 2 cm, and 12% had human epidermal growth factor receptor 2–positive breast cancer. Their median age was 43 years.
Outcomes
At 5 years, exemestane plus OFS significantly improved the primary endpoint of disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (hazard ratio, 0.72; P = .0002), Dr. Pagani said.
No striking heterogeneity of treatment effect was observed in prospectively planned subgroup analyses including the cohorts defined by trial, chemotherapy stratum, and node status.
"The relative and absolute differences at 5 years compare favorably with those reported in the practice-changing BIG 1-98 and ATAC [Arimidex, Tamoxifen, Alone or in Combination] trials of aromatase inhibitors vs. tamoxifen in postmenopausal women," she said.
At 5 years, 92.8% of women assigned to receive exemestane plus ovarian suppression were free from breast cancer vs. 88.8% of those given tamoxifen plus ovarian suppression (HR, 0.66; P less than .0001).
The rate of freedom from distant recurrence at 5 years was also superior in the exemestane group (93.8% vs. 92%; HR, 0.78; P = .02). In all, 60% of first events involved distant sites.
These benefits, however, have yet to translate into a significant overall survival benefit at 5 years for exemestane plus ovarian suppression, compared with tamoxifen plus ovarian suppression (95.9% vs. 96.9%; HR, 1.14; P = .37), said Dr. Pagani, who added that conclusions about long-term survival are premature at this early follow-up.
Where do we go from here?
ASCO immediate past-president Dr. Clifford Hudis said in a press briefing that the joint analysis provides long-awaited and actionable information on how best to treat premenopausal women with hormone-sensitive breast cancer who appear cured after surgery, but that data from the tamoxifen-alone arm in SOFT are needed to change practice for those unconvinced about the need for ovarian suppression.
Dr. Davidson said she’s left pondering how the results will be integrated into practice. Will clinicians use 10 years of tamoxifen, as supported by the ATLAS and aTTOM trials, or will they use an extended adjuvant approach of 5 years of tamoxifen followed by a switch to 5 years of AI for women who become postmenopausal during their tamoxifen, as supported by the MA 17 trial? It’s also possible some will follow the lead set by TEXT/SOFT and use 5 years of ovarian suppression and AI.
"If the benefits of OFS with AI hold up, we may want to revisit the role of oophorectomy in selected patients, who want to avoid injections and have a permanent menopause," she added. "We will need to make sure we maximize bisphosphonates for bone health, but I’m not prepared to use bisphosphonates as a routine form of adjuvant therapy in these women just yet."
Finally, Dr. Davidson said long-term follow-up of TEXT/SOFT is vital for both benefit and toxicity. Though overall compliance was good, she noted earlier in her talk that 16% of women on exemestane plus OFS prematurely stopped therapy vs. 11% on tamoxifen plus OFS. "Financial toxicity" is also an issue, with the wholesale acquisition cost at her institution for 1 year of exemestane 25 mg daily at $7,344 vs. $1,369 for tamoxifen, she said.
Dr. Pagani stressed during the press briefing that the results do not mean all premenopausal women should be given an AI plus ovarian suppression, but that the decision should be individualized with input from the physician and patient.
The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute (NCI). Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and National Institutes of Health (NIH).
AT THE ASCO ANNUAL MEETING 2014
Key clinical point: Exemestane plus OFS is a new treatment option in the setting of premenopausal hormone-sensitive early breast cancer.
Major finding: Exemestane plus OFS significantly improved disease-free survival from 87.3% with tamoxifen plus OFS to 91.1% (HR, 0.72; P = .0002).
Data source: Joint analysis of two phase III studies in 4,690 premenopausal women with hormone receptor-positive, early breast cancer.
Disclosures: The research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the NCI. Dr. Pagani reported research funding from Ipsen and Pfizer. Dr. Davidson reported research funding from the Breast Cancer Research Foundation and the NIH.
Ruxolitinib improves disease control in PV
©ASCO/Phil McCarten
CHICAGO—The JAK1/2 inhibitor ruxolitinib may be a “valuable new treatment option” for patients with polycythemia vera (PV) who cannot tolerate or are resistant to hydroxyurea, according to a speaker at the 2014 ASCO Annual Meeting.
Results of the phase 3 RESPONSE trial showed that ruxolitinib can reduce spleen size in these patients and improve hematocrit control without the need for phlebotomy.
And the drug was generally well-tolerated.
“Patients with PV may not have their disease controlled with existing therapies, increasing their risk for cardiovascular complications,” said Srdan Verstovsek, MD, PhD, of MD Anderson Cancer Center in Houston, Texas.
“In the RESPONSE trial, patients treated with ruxolitinib showed better disease control and improved symptom management compared to [patients who received] current therapies.”
Dr Verstovsek presented results from the trial at ASCO as abstract 7026. RESPONSE was funded by Incyte Corporation, the company developing ruxolitinib.
The study has enrolled 222 patients with PV that is resistant to or intolerant of hydroxyurea. Patients were randomized to receive either ruxolitinib at a starting dose of 10 mg twice-daily or best available therapy (BAT). The ruxolitinib dose was adjusted as needed throughout the study.
At week 32, 77% of patients on ruxolitinib and 20% on BAT achieved hematocrit control or spleen reduction.
The primary endpoint of the study was the proportion of patients whose hematocrit was controlled without phlebotomy from week 8 through 32 and whose spleen volume was reduced by 35% or more from baseline as assessed by imaging at 32 weeks.
Twenty-one percent of patients in the ruxolitinib arm achieved this endpoint, compared to 1% of patients in the BAT arm.
“Ninety-one percent of patients who achieved the primary end point had a confirmed response at 48 weeks,” Dr Verstovsek said.
He also noted that nearly half of ruxolitinib-treated patients had a 50% or greater reduction in debilitating PV symptoms, compared to 5% of those on BAT.
Patients treated with ruxolitinib also experienced a reduction in night sweats and itchiness. In addition, a greater proportion of patients in the ruxolitinib arm achieved complete hematologic response when compared to the BAT arm—24% and 9%, respectively.
Ruxolitinib was generally well-tolerated, Dr Verstovsek said, noting that 85% of patients were still receiving the drug at a median follow-up of 81 weeks.
However, 3.6% of patients on ruxolitinib discontinued treatment due to adverse events, compared to 1.8% of patients on BAT.
Most adverse events observed in the ruxolitinib arm were grade 1 or 2 and were consistent with those previously seen in ruxolitinib studies in PV and myelofibrosis.
Few patients developed grade 3 or 4 cytopenias. Within the first 32 weeks of treatment, grade 3 or 4 hematologic adverse events in the ruxolitinib treatment arm were anemia (1.8%) and thrombocytopenia (5.5%). Fewer patients treated with ruxolitinib experienced thromboembolic events when compared to those who received BAT.
The most common non-hematologic adverse events were headache, diarrhea, and fatigue, which were mainly grade 1 or 2. Dr Verstovsek noted that herpes zoster infection was higher in the ruxolitinib arm than in the BAT arm.
Ruxolitinib is currently approved in more than 60 countries for patients with myelofibrosis. Global regulatory filings for PV are underway based on the RESPONSE data. 
©ASCO/Phil McCarten
CHICAGO—The JAK1/2 inhibitor ruxolitinib may be a “valuable new treatment option” for patients with polycythemia vera (PV) who cannot tolerate or are resistant to hydroxyurea, according to a speaker at the 2014 ASCO Annual Meeting.
Results of the phase 3 RESPONSE trial showed that ruxolitinib can reduce spleen size in these patients and improve hematocrit control without the need for phlebotomy.
And the drug was generally well-tolerated.
“Patients with PV may not have their disease controlled with existing therapies, increasing their risk for cardiovascular complications,” said Srdan Verstovsek, MD, PhD, of MD Anderson Cancer Center in Houston, Texas.
“In the RESPONSE trial, patients treated with ruxolitinib showed better disease control and improved symptom management compared to [patients who received] current therapies.”
Dr Verstovsek presented results from the trial at ASCO as abstract 7026. RESPONSE was funded by Incyte Corporation, the company developing ruxolitinib.
The study has enrolled 222 patients with PV that is resistant to or intolerant of hydroxyurea. Patients were randomized to receive either ruxolitinib at a starting dose of 10 mg twice-daily or best available therapy (BAT). The ruxolitinib dose was adjusted as needed throughout the study.
At week 32, 77% of patients on ruxolitinib and 20% on BAT achieved hematocrit control or spleen reduction.
The primary endpoint of the study was the proportion of patients whose hematocrit was controlled without phlebotomy from week 8 through 32 and whose spleen volume was reduced by 35% or more from baseline as assessed by imaging at 32 weeks.
Twenty-one percent of patients in the ruxolitinib arm achieved this endpoint, compared to 1% of patients in the BAT arm.
“Ninety-one percent of patients who achieved the primary end point had a confirmed response at 48 weeks,” Dr Verstovsek said.
He also noted that nearly half of ruxolitinib-treated patients had a 50% or greater reduction in debilitating PV symptoms, compared to 5% of those on BAT.
Patients treated with ruxolitinib also experienced a reduction in night sweats and itchiness. In addition, a greater proportion of patients in the ruxolitinib arm achieved complete hematologic response when compared to the BAT arm—24% and 9%, respectively.
Ruxolitinib was generally well-tolerated, Dr Verstovsek said, noting that 85% of patients were still receiving the drug at a median follow-up of 81 weeks.
However, 3.6% of patients on ruxolitinib discontinued treatment due to adverse events, compared to 1.8% of patients on BAT.
Most adverse events observed in the ruxolitinib arm were grade 1 or 2 and were consistent with those previously seen in ruxolitinib studies in PV and myelofibrosis.
Few patients developed grade 3 or 4 cytopenias. Within the first 32 weeks of treatment, grade 3 or 4 hematologic adverse events in the ruxolitinib treatment arm were anemia (1.8%) and thrombocytopenia (5.5%). Fewer patients treated with ruxolitinib experienced thromboembolic events when compared to those who received BAT.
The most common non-hematologic adverse events were headache, diarrhea, and fatigue, which were mainly grade 1 or 2. Dr Verstovsek noted that herpes zoster infection was higher in the ruxolitinib arm than in the BAT arm.
Ruxolitinib is currently approved in more than 60 countries for patients with myelofibrosis. Global regulatory filings for PV are underway based on the RESPONSE data.
©ASCO/Phil McCarten
CHICAGO—The JAK1/2 inhibitor ruxolitinib may be a “valuable new treatment option” for patients with polycythemia vera (PV) who cannot tolerate or are resistant to hydroxyurea, according to a speaker at the 2014 ASCO Annual Meeting.
Results of the phase 3 RESPONSE trial showed that ruxolitinib can reduce spleen size in these patients and improve hematocrit control without the need for phlebotomy.
And the drug was generally well-tolerated.
“Patients with PV may not have their disease controlled with existing therapies, increasing their risk for cardiovascular complications,” said Srdan Verstovsek, MD, PhD, of MD Anderson Cancer Center in Houston, Texas.
“In the RESPONSE trial, patients treated with ruxolitinib showed better disease control and improved symptom management compared to [patients who received] current therapies.”
Dr Verstovsek presented results from the trial at ASCO as abstract 7026. RESPONSE was funded by Incyte Corporation, the company developing ruxolitinib.
The study has enrolled 222 patients with PV that is resistant to or intolerant of hydroxyurea. Patients were randomized to receive either ruxolitinib at a starting dose of 10 mg twice-daily or best available therapy (BAT). The ruxolitinib dose was adjusted as needed throughout the study.
At week 32, 77% of patients on ruxolitinib and 20% on BAT achieved hematocrit control or spleen reduction.
The primary endpoint of the study was the proportion of patients whose hematocrit was controlled without phlebotomy from week 8 through 32 and whose spleen volume was reduced by 35% or more from baseline as assessed by imaging at 32 weeks.
Twenty-one percent of patients in the ruxolitinib arm achieved this endpoint, compared to 1% of patients in the BAT arm.
“Ninety-one percent of patients who achieved the primary end point had a confirmed response at 48 weeks,” Dr Verstovsek said.
He also noted that nearly half of ruxolitinib-treated patients had a 50% or greater reduction in debilitating PV symptoms, compared to 5% of those on BAT.
Patients treated with ruxolitinib also experienced a reduction in night sweats and itchiness. In addition, a greater proportion of patients in the ruxolitinib arm achieved complete hematologic response when compared to the BAT arm—24% and 9%, respectively.
Ruxolitinib was generally well-tolerated, Dr Verstovsek said, noting that 85% of patients were still receiving the drug at a median follow-up of 81 weeks.
However, 3.6% of patients on ruxolitinib discontinued treatment due to adverse events, compared to 1.8% of patients on BAT.
Most adverse events observed in the ruxolitinib arm were grade 1 or 2 and were consistent with those previously seen in ruxolitinib studies in PV and myelofibrosis.
Few patients developed grade 3 or 4 cytopenias. Within the first 32 weeks of treatment, grade 3 or 4 hematologic adverse events in the ruxolitinib treatment arm were anemia (1.8%) and thrombocytopenia (5.5%). Fewer patients treated with ruxolitinib experienced thromboembolic events when compared to those who received BAT.
The most common non-hematologic adverse events were headache, diarrhea, and fatigue, which were mainly grade 1 or 2. Dr Verstovsek noted that herpes zoster infection was higher in the ruxolitinib arm than in the BAT arm.
Ruxolitinib is currently approved in more than 60 countries for patients with myelofibrosis. Global regulatory filings for PV are underway based on the RESPONSE data.
Treating HIV+ lymphoma patients
©ASCO/Brian Powers
CHICAGO—Hepatitis C reactivation does not worsen survival outcomes for HIV-positive patients diagnosed with lymphoma, new research indicates.
The study showed these patients can tolerate chemotherapy without adverse outcomes and are therefore eligible for aggressive treatment.
They should be closely monitored, however, according to study investigator Stefan K. Barta, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania.
Dr Barta and his colleagues presented results observed in HIV-positive lymphoma patients at the 2014 ASCO Annual Meeting as abstract 8578.
The team noted that more than a quarter of HIV-positive patients are also infected with the hepatitis C virus (HCV), which may complicate treatment and care decisions after a cancer diagnosis.
“Patients undergoing chemotherapy can experience reactivation of the hepatitis C virus, which, in turn, can lead to liver failure,” Dr Barta said. “This means we have to dose-reduce chemotherapy, which could negatively affect outcomes.”
In addition, HIV-positive patients often take a host of other medications, including anti-retrovirals, which makes them especially vulnerable to side effects.
However, Dr Barta said these potential risks shouldn’t deter oncologists from treating these patients with chemotherapy because he and his colleagues found that reactivation of HCV did not worsen survival outcomes in this population.
The researchers analyzed the medical records of 190 HIV-positive patients who had been diagnosed with lymphoma at the Albert Einstein Cancer Center in Bronx, New York, from 1997 to 2013. Patients with primary central nervous system lymphomas were excluded.
Fifty-three (28%) eligible patients were also infected with HCV. The virus reactivated in 17 of those patients, or about one-third of the patient population infected with HCV, during treatment.
Patients infected with HCV had an overall survival of 59.7 months, compared to 88.6 months for patients with neither HCV nor hepatitis B virus (HBV).
However, that survival advantage vanished when the researchers adjusted for variables including age, sex, race, CD4 count, the presence of cirrhosis, type of lymphoma, and levels of lactate dehydrogenase (LDH).
The multivariate analysis showed that co-infection with HCV was not associated with lower overall survival in lymphoma patients.
At the same time, the researchers did find worse overall survival outcomes associated with low CD4 count (below 100 cells/cubic millimeter), a diagnosis of non-Hodgkin lymphoma, advanced stage disease, LDH levels over 190, or cirrhosis.
Dr Barta said he hopes this research will open cancer trials up to an understudied patient population. HIV-positive patients with HCV are often excluded from these trials because of concerns about liver failure and toxicity arising from the interaction of retroviral medications with chemotherapy.
“This is really important for a large proportion of patients,” he said. “We want to assure researchers that these patients, as long as they have adequate liver function, should also be enrolled in clinical trials.”
©ASCO/Brian Powers
CHICAGO—Hepatitis C reactivation does not worsen survival outcomes for HIV-positive patients diagnosed with lymphoma, new research indicates.
The study showed these patients can tolerate chemotherapy without adverse outcomes and are therefore eligible for aggressive treatment.
They should be closely monitored, however, according to study investigator Stefan K. Barta, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania.
Dr Barta and his colleagues presented results observed in HIV-positive lymphoma patients at the 2014 ASCO Annual Meeting as abstract 8578.
The team noted that more than a quarter of HIV-positive patients are also infected with the hepatitis C virus (HCV), which may complicate treatment and care decisions after a cancer diagnosis.
“Patients undergoing chemotherapy can experience reactivation of the hepatitis C virus, which, in turn, can lead to liver failure,” Dr Barta said. “This means we have to dose-reduce chemotherapy, which could negatively affect outcomes.”
In addition, HIV-positive patients often take a host of other medications, including anti-retrovirals, which makes them especially vulnerable to side effects.
However, Dr Barta said these potential risks shouldn’t deter oncologists from treating these patients with chemotherapy because he and his colleagues found that reactivation of HCV did not worsen survival outcomes in this population.
The researchers analyzed the medical records of 190 HIV-positive patients who had been diagnosed with lymphoma at the Albert Einstein Cancer Center in Bronx, New York, from 1997 to 2013. Patients with primary central nervous system lymphomas were excluded.
Fifty-three (28%) eligible patients were also infected with HCV. The virus reactivated in 17 of those patients, or about one-third of the patient population infected with HCV, during treatment.
Patients infected with HCV had an overall survival of 59.7 months, compared to 88.6 months for patients with neither HCV nor hepatitis B virus (HBV).
However, that survival advantage vanished when the researchers adjusted for variables including age, sex, race, CD4 count, the presence of cirrhosis, type of lymphoma, and levels of lactate dehydrogenase (LDH).
The multivariate analysis showed that co-infection with HCV was not associated with lower overall survival in lymphoma patients.
At the same time, the researchers did find worse overall survival outcomes associated with low CD4 count (below 100 cells/cubic millimeter), a diagnosis of non-Hodgkin lymphoma, advanced stage disease, LDH levels over 190, or cirrhosis.
Dr Barta said he hopes this research will open cancer trials up to an understudied patient population. HIV-positive patients with HCV are often excluded from these trials because of concerns about liver failure and toxicity arising from the interaction of retroviral medications with chemotherapy.
“This is really important for a large proportion of patients,” he said. “We want to assure researchers that these patients, as long as they have adequate liver function, should also be enrolled in clinical trials.”
©ASCO/Brian Powers
CHICAGO—Hepatitis C reactivation does not worsen survival outcomes for HIV-positive patients diagnosed with lymphoma, new research indicates.
The study showed these patients can tolerate chemotherapy without adverse outcomes and are therefore eligible for aggressive treatment.
They should be closely monitored, however, according to study investigator Stefan K. Barta, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania.
Dr Barta and his colleagues presented results observed in HIV-positive lymphoma patients at the 2014 ASCO Annual Meeting as abstract 8578.
The team noted that more than a quarter of HIV-positive patients are also infected with the hepatitis C virus (HCV), which may complicate treatment and care decisions after a cancer diagnosis.
“Patients undergoing chemotherapy can experience reactivation of the hepatitis C virus, which, in turn, can lead to liver failure,” Dr Barta said. “This means we have to dose-reduce chemotherapy, which could negatively affect outcomes.”
In addition, HIV-positive patients often take a host of other medications, including anti-retrovirals, which makes them especially vulnerable to side effects.
However, Dr Barta said these potential risks shouldn’t deter oncologists from treating these patients with chemotherapy because he and his colleagues found that reactivation of HCV did not worsen survival outcomes in this population.
The researchers analyzed the medical records of 190 HIV-positive patients who had been diagnosed with lymphoma at the Albert Einstein Cancer Center in Bronx, New York, from 1997 to 2013. Patients with primary central nervous system lymphomas were excluded.
Fifty-three (28%) eligible patients were also infected with HCV. The virus reactivated in 17 of those patients, or about one-third of the patient population infected with HCV, during treatment.
Patients infected with HCV had an overall survival of 59.7 months, compared to 88.6 months for patients with neither HCV nor hepatitis B virus (HBV).
However, that survival advantage vanished when the researchers adjusted for variables including age, sex, race, CD4 count, the presence of cirrhosis, type of lymphoma, and levels of lactate dehydrogenase (LDH).
The multivariate analysis showed that co-infection with HCV was not associated with lower overall survival in lymphoma patients.
At the same time, the researchers did find worse overall survival outcomes associated with low CD4 count (below 100 cells/cubic millimeter), a diagnosis of non-Hodgkin lymphoma, advanced stage disease, LDH levels over 190, or cirrhosis.
Dr Barta said he hopes this research will open cancer trials up to an understudied patient population. HIV-positive patients with HCV are often excluded from these trials because of concerns about liver failure and toxicity arising from the interaction of retroviral medications with chemotherapy.
“This is really important for a large proportion of patients,” he said. “We want to assure researchers that these patients, as long as they have adequate liver function, should also be enrolled in clinical trials.”
Palliative care at time of cancer diagnosis improves survival
CHICAGO – Early palliative care delivered almost exclusively by telephone improved survival among patients with advanced cancer in the ENABLE III study.
After a median follow-up of a little more than 1 year, 46% of patients receiving palliative care from the time of cancer diagnosis and 54% of those with delayed palliative care had died.
Overall median survival was 18.3 months for the immediate group and 11.9 months for the delayed group (P = .17).
In preplanned analyses, the risk of death at 1 year was significantly lower in the immediate group (hazard ratio 0.72; P = .003), with a catch-up effect thereafter, Marie Bakitas, DNSc, reported at the annual meeting of the American Society of Clinical Oncology.
"Enhanced medical care, reduced aggressive care and chemotherapy use, longer access to hospice, and biologic impacts of improved quality of life have all been proposed as mechanisms to explain this survival advantage," Dr. Bakitas said. "However, at the present time, we do not have the data to support a particular mechanism and we are actively exploring this question through secondary analyses."
ENABLE (Educate, Nurture, Advise, Before Life Ends) III is the first study to examine the timing of early palliative care, but not the first to identify a survival advantage.
A recent study (N. Engl. J. Med. 2010:363:733-42) found that patients with metastatic non–small cell lung cancer (NSCLC) who received palliative care at the time of randomization lived a significant 2.7 months longer than did those receiving standard oncologic care, despite receiving significantly less aggressive end-of-life care (33% vs. 54%).
In ENABLE III, 207 patients with advanced cancer, and their caregivers, were randomized as a dyad to begin usual cancer care plus the intervention at the time of diagnosis (immediate group) or usual care alone for 3 months followed by the intervention (delayed group).
The intervention consisted of a traditional outpatient palliative care consult and six weekly structured telephone calls with a nurse coach using a guidebook that covers such topics as problem solving, symptom management, communication, and advanced care planning, explained Dr. Bakitas, the Marie O’Koren Endowed Chair and Professor, School of Nursing, and associate director of the Center for Palliative and Supportive Care, University of Alabama, Birmingham.
Usual care included the clinical consult, but not the telephone intervention.
The participants’ mean age was 64 years, half were male, 60% lived in a rural area, and 65% were married or living with a partner. Lung cancer was the most common diagnosis at 42%.
At baseline, 75% of patients were receiving chemotherapy, 19% were undergoing radiation, and 43% had an advanced directive completed at diagnosis.
Unlike the group’s prior trial comparing palliative care to usual care at 3 months, immediate versus delayed palliative care did not lead to significant improvements in quality of life on the Functional Assessment of Chronic Illness Therapy-Palliative care scale (129.9 vs. 127.2; P = .34), mood on the Center for Epidemiologic Studies Depression scale (11.2 vs. 10.8; P = .33), or symptom impact on the Quality of Life at the End of Life symptom impact subscale (11.4 vs. 12.2; P = .09).
One plausible reason for the findings is that there may not have been enough care differences between the two groups, with 40% of the delayed group receiving their first palliative care contact an average of 30 days before they were scheduled to do so on day 84, Dr. Bakitas said.
Second, difficulties in accrual and decreased study power may have made it difficult to pick up between-group differences on the subjective instruments, resulting in a type 2 error.
"A 3-month delay is still very early," Dr. Bakitas said.
She noted that early intervention allowed the palliative care team to have contact with patients for 1 year on average (range 240-493 days), compared with a median of 41-90 days from referral to death reported for outpatient clinics in a national survey of 142 National Cancer Institute and non-NCI cancer centers (JAMA 2010;303:1054-61).
Resource and chemotherapy use in ENABLE III was also comparable in both groups. Decedents in the immediate and delayed groups spent a median of 5 and 6 days, respectively, in hospital in the 7-9 months preceding death, while 8% and 5% received chemotherapy in the last 2 weeks of life.
This compares favorably with a national average of more than 8 hospital days in the last 6 months of life observed in the 2014 Dartmouth Atlas of Health Care, and a chemotherapy rate of 17.5% reported in the previously noted NSCLC study, Dr. Bakitas said.
She called for more studies of early palliative care to determine the optimal timing, personnel, essential elements, and mechanisms of improved survival.
"While the benefits of these approaches have been demonstrated when provided early after a cancer diagnosis, in practice these potentially beneficial palliative care services are often provided very late, sometimes hours or weeks before death," Dr. Bakitas said. "This trend is likely to continue in the absence of clear direction on the very pragmatic questions of who, what, and when."
The study was funded by National Institute for Nursing Research. Dr. Bakitas reported having no relevant disclosures.
Palliative care support buoys caregivers of advanced cancer patients
Providing early palliative care support to caregivers of advanced cancer patients improves their quality of life, depression, and stress burden, the ENABLE III study found.
"Similar to patients, waiting to provide these caregiver services until patients are in their last weeks to days of life may not adequately address the distress that they experience," Nick Dionne-Odom, Ph.D., RN, said at the meeting.
Caregivers for the 13 million cancer patients in the United States living with advanced disease can spend up to 8 hours per day providing assistance in activities that include symptom management, emotional and spiritual support, meal preparation, arranging medical appointments, and transportation.
The combination of this burden and witnessing someone close to you struggle with illness can cause psychological distress equal to or sometimes greater than that experienced by the patient, said Dr. Dionne-Odom, a postdoctoral fellow at the University of Alabama at Birmingham.
In ENABLE III, 122 caregivers were randomized at the time of the patient’s cancer diagnosis or 12 weeks later to a palliative care intervention that consisted of three weekly structured educational telephone calls from an advanced practice nurse coach, monthly check-in calls to address new or ongoing issues, and a bereavement call for caregivers whose loved ones died.
Caregivers were not restricted to family members, but could include close friends and even neighbors. Their mean age was 60 years, 79% were female, 75% were spouses, and all had at least a high school education.
At 12 weeks from the start of the intervention, caregivers in the immediate versus delayed group had significantly better quality of life on the Caregiver Quality of Life Index–Cancer scale (mean 50.2 vs. 56.1; P = .02) and less depressive symptoms on the Center for Epidemiologic Studies Depression (CESD) scale (10.2 vs. 16.6; P = .0006), Dr. Dionne-Odom said. Notably, the delayed group surpassed the clinical cutoff for depression of 16 on the CESD scale, he added.
The intervention did not appear to change the perception among caregivers of what was demanded of them by the patient or their objective burden, though there was a trend among the immediate group for improved caregiver stress burden on the Montgomery Borgatta Caregiver Burden Scale (13.2 vs. 13.8; P = .10).
There was no significant difference between groups in depression or grief scores for caregivers of decedents. A difference may have been detected with a larger sample size, he said, adding that prior studies have shown that reducing caregiver stress before patients’ death is associated with better bereavement adjustment.
As for why caregivers appear to benefit more than the patients from the parallel palliative care interventions, Dr. Bakitas said in an interview it may be the timing of the assessments, adding that other studies have shown an impact of palliative care at 4 months, but not at 3 months.
CHICAGO – Early palliative care delivered almost exclusively by telephone improved survival among patients with advanced cancer in the ENABLE III study.
After a median follow-up of a little more than 1 year, 46% of patients receiving palliative care from the time of cancer diagnosis and 54% of those with delayed palliative care had died.
Overall median survival was 18.3 months for the immediate group and 11.9 months for the delayed group (P = .17).
In preplanned analyses, the risk of death at 1 year was significantly lower in the immediate group (hazard ratio 0.72; P = .003), with a catch-up effect thereafter, Marie Bakitas, DNSc, reported at the annual meeting of the American Society of Clinical Oncology.
"Enhanced medical care, reduced aggressive care and chemotherapy use, longer access to hospice, and biologic impacts of improved quality of life have all been proposed as mechanisms to explain this survival advantage," Dr. Bakitas said. "However, at the present time, we do not have the data to support a particular mechanism and we are actively exploring this question through secondary analyses."
ENABLE (Educate, Nurture, Advise, Before Life Ends) III is the first study to examine the timing of early palliative care, but not the first to identify a survival advantage.
A recent study (N. Engl. J. Med. 2010:363:733-42) found that patients with metastatic non–small cell lung cancer (NSCLC) who received palliative care at the time of randomization lived a significant 2.7 months longer than did those receiving standard oncologic care, despite receiving significantly less aggressive end-of-life care (33% vs. 54%).
In ENABLE III, 207 patients with advanced cancer, and their caregivers, were randomized as a dyad to begin usual cancer care plus the intervention at the time of diagnosis (immediate group) or usual care alone for 3 months followed by the intervention (delayed group).
The intervention consisted of a traditional outpatient palliative care consult and six weekly structured telephone calls with a nurse coach using a guidebook that covers such topics as problem solving, symptom management, communication, and advanced care planning, explained Dr. Bakitas, the Marie O’Koren Endowed Chair and Professor, School of Nursing, and associate director of the Center for Palliative and Supportive Care, University of Alabama, Birmingham.
Usual care included the clinical consult, but not the telephone intervention.
The participants’ mean age was 64 years, half were male, 60% lived in a rural area, and 65% were married or living with a partner. Lung cancer was the most common diagnosis at 42%.
At baseline, 75% of patients were receiving chemotherapy, 19% were undergoing radiation, and 43% had an advanced directive completed at diagnosis.
Unlike the group’s prior trial comparing palliative care to usual care at 3 months, immediate versus delayed palliative care did not lead to significant improvements in quality of life on the Functional Assessment of Chronic Illness Therapy-Palliative care scale (129.9 vs. 127.2; P = .34), mood on the Center for Epidemiologic Studies Depression scale (11.2 vs. 10.8; P = .33), or symptom impact on the Quality of Life at the End of Life symptom impact subscale (11.4 vs. 12.2; P = .09).
One plausible reason for the findings is that there may not have been enough care differences between the two groups, with 40% of the delayed group receiving their first palliative care contact an average of 30 days before they were scheduled to do so on day 84, Dr. Bakitas said.
Second, difficulties in accrual and decreased study power may have made it difficult to pick up between-group differences on the subjective instruments, resulting in a type 2 error.
"A 3-month delay is still very early," Dr. Bakitas said.
She noted that early intervention allowed the palliative care team to have contact with patients for 1 year on average (range 240-493 days), compared with a median of 41-90 days from referral to death reported for outpatient clinics in a national survey of 142 National Cancer Institute and non-NCI cancer centers (JAMA 2010;303:1054-61).
Resource and chemotherapy use in ENABLE III was also comparable in both groups. Decedents in the immediate and delayed groups spent a median of 5 and 6 days, respectively, in hospital in the 7-9 months preceding death, while 8% and 5% received chemotherapy in the last 2 weeks of life.
This compares favorably with a national average of more than 8 hospital days in the last 6 months of life observed in the 2014 Dartmouth Atlas of Health Care, and a chemotherapy rate of 17.5% reported in the previously noted NSCLC study, Dr. Bakitas said.
She called for more studies of early palliative care to determine the optimal timing, personnel, essential elements, and mechanisms of improved survival.
"While the benefits of these approaches have been demonstrated when provided early after a cancer diagnosis, in practice these potentially beneficial palliative care services are often provided very late, sometimes hours or weeks before death," Dr. Bakitas said. "This trend is likely to continue in the absence of clear direction on the very pragmatic questions of who, what, and when."
The study was funded by National Institute for Nursing Research. Dr. Bakitas reported having no relevant disclosures.
Palliative care support buoys caregivers of advanced cancer patients
Providing early palliative care support to caregivers of advanced cancer patients improves their quality of life, depression, and stress burden, the ENABLE III study found.
"Similar to patients, waiting to provide these caregiver services until patients are in their last weeks to days of life may not adequately address the distress that they experience," Nick Dionne-Odom, Ph.D., RN, said at the meeting.
Caregivers for the 13 million cancer patients in the United States living with advanced disease can spend up to 8 hours per day providing assistance in activities that include symptom management, emotional and spiritual support, meal preparation, arranging medical appointments, and transportation.
The combination of this burden and witnessing someone close to you struggle with illness can cause psychological distress equal to or sometimes greater than that experienced by the patient, said Dr. Dionne-Odom, a postdoctoral fellow at the University of Alabama at Birmingham.
In ENABLE III, 122 caregivers were randomized at the time of the patient’s cancer diagnosis or 12 weeks later to a palliative care intervention that consisted of three weekly structured educational telephone calls from an advanced practice nurse coach, monthly check-in calls to address new or ongoing issues, and a bereavement call for caregivers whose loved ones died.
Caregivers were not restricted to family members, but could include close friends and even neighbors. Their mean age was 60 years, 79% were female, 75% were spouses, and all had at least a high school education.
At 12 weeks from the start of the intervention, caregivers in the immediate versus delayed group had significantly better quality of life on the Caregiver Quality of Life Index–Cancer scale (mean 50.2 vs. 56.1; P = .02) and less depressive symptoms on the Center for Epidemiologic Studies Depression (CESD) scale (10.2 vs. 16.6; P = .0006), Dr. Dionne-Odom said. Notably, the delayed group surpassed the clinical cutoff for depression of 16 on the CESD scale, he added.
The intervention did not appear to change the perception among caregivers of what was demanded of them by the patient or their objective burden, though there was a trend among the immediate group for improved caregiver stress burden on the Montgomery Borgatta Caregiver Burden Scale (13.2 vs. 13.8; P = .10).
There was no significant difference between groups in depression or grief scores for caregivers of decedents. A difference may have been detected with a larger sample size, he said, adding that prior studies have shown that reducing caregiver stress before patients’ death is associated with better bereavement adjustment.
As for why caregivers appear to benefit more than the patients from the parallel palliative care interventions, Dr. Bakitas said in an interview it may be the timing of the assessments, adding that other studies have shown an impact of palliative care at 4 months, but not at 3 months.
CHICAGO – Early palliative care delivered almost exclusively by telephone improved survival among patients with advanced cancer in the ENABLE III study.
After a median follow-up of a little more than 1 year, 46% of patients receiving palliative care from the time of cancer diagnosis and 54% of those with delayed palliative care had died.
Overall median survival was 18.3 months for the immediate group and 11.9 months for the delayed group (P = .17).
In preplanned analyses, the risk of death at 1 year was significantly lower in the immediate group (hazard ratio 0.72; P = .003), with a catch-up effect thereafter, Marie Bakitas, DNSc, reported at the annual meeting of the American Society of Clinical Oncology.
"Enhanced medical care, reduced aggressive care and chemotherapy use, longer access to hospice, and biologic impacts of improved quality of life have all been proposed as mechanisms to explain this survival advantage," Dr. Bakitas said. "However, at the present time, we do not have the data to support a particular mechanism and we are actively exploring this question through secondary analyses."
ENABLE (Educate, Nurture, Advise, Before Life Ends) III is the first study to examine the timing of early palliative care, but not the first to identify a survival advantage.
A recent study (N. Engl. J. Med. 2010:363:733-42) found that patients with metastatic non–small cell lung cancer (NSCLC) who received palliative care at the time of randomization lived a significant 2.7 months longer than did those receiving standard oncologic care, despite receiving significantly less aggressive end-of-life care (33% vs. 54%).
In ENABLE III, 207 patients with advanced cancer, and their caregivers, were randomized as a dyad to begin usual cancer care plus the intervention at the time of diagnosis (immediate group) or usual care alone for 3 months followed by the intervention (delayed group).
The intervention consisted of a traditional outpatient palliative care consult and six weekly structured telephone calls with a nurse coach using a guidebook that covers such topics as problem solving, symptom management, communication, and advanced care planning, explained Dr. Bakitas, the Marie O’Koren Endowed Chair and Professor, School of Nursing, and associate director of the Center for Palliative and Supportive Care, University of Alabama, Birmingham.
Usual care included the clinical consult, but not the telephone intervention.
The participants’ mean age was 64 years, half were male, 60% lived in a rural area, and 65% were married or living with a partner. Lung cancer was the most common diagnosis at 42%.
At baseline, 75% of patients were receiving chemotherapy, 19% were undergoing radiation, and 43% had an advanced directive completed at diagnosis.
Unlike the group’s prior trial comparing palliative care to usual care at 3 months, immediate versus delayed palliative care did not lead to significant improvements in quality of life on the Functional Assessment of Chronic Illness Therapy-Palliative care scale (129.9 vs. 127.2; P = .34), mood on the Center for Epidemiologic Studies Depression scale (11.2 vs. 10.8; P = .33), or symptom impact on the Quality of Life at the End of Life symptom impact subscale (11.4 vs. 12.2; P = .09).
One plausible reason for the findings is that there may not have been enough care differences between the two groups, with 40% of the delayed group receiving their first palliative care contact an average of 30 days before they were scheduled to do so on day 84, Dr. Bakitas said.
Second, difficulties in accrual and decreased study power may have made it difficult to pick up between-group differences on the subjective instruments, resulting in a type 2 error.
"A 3-month delay is still very early," Dr. Bakitas said.
She noted that early intervention allowed the palliative care team to have contact with patients for 1 year on average (range 240-493 days), compared with a median of 41-90 days from referral to death reported for outpatient clinics in a national survey of 142 National Cancer Institute and non-NCI cancer centers (JAMA 2010;303:1054-61).
Resource and chemotherapy use in ENABLE III was also comparable in both groups. Decedents in the immediate and delayed groups spent a median of 5 and 6 days, respectively, in hospital in the 7-9 months preceding death, while 8% and 5% received chemotherapy in the last 2 weeks of life.
This compares favorably with a national average of more than 8 hospital days in the last 6 months of life observed in the 2014 Dartmouth Atlas of Health Care, and a chemotherapy rate of 17.5% reported in the previously noted NSCLC study, Dr. Bakitas said.
She called for more studies of early palliative care to determine the optimal timing, personnel, essential elements, and mechanisms of improved survival.
"While the benefits of these approaches have been demonstrated when provided early after a cancer diagnosis, in practice these potentially beneficial palliative care services are often provided very late, sometimes hours or weeks before death," Dr. Bakitas said. "This trend is likely to continue in the absence of clear direction on the very pragmatic questions of who, what, and when."
The study was funded by National Institute for Nursing Research. Dr. Bakitas reported having no relevant disclosures.
Palliative care support buoys caregivers of advanced cancer patients
Providing early palliative care support to caregivers of advanced cancer patients improves their quality of life, depression, and stress burden, the ENABLE III study found.
"Similar to patients, waiting to provide these caregiver services until patients are in their last weeks to days of life may not adequately address the distress that they experience," Nick Dionne-Odom, Ph.D., RN, said at the meeting.
Caregivers for the 13 million cancer patients in the United States living with advanced disease can spend up to 8 hours per day providing assistance in activities that include symptom management, emotional and spiritual support, meal preparation, arranging medical appointments, and transportation.
The combination of this burden and witnessing someone close to you struggle with illness can cause psychological distress equal to or sometimes greater than that experienced by the patient, said Dr. Dionne-Odom, a postdoctoral fellow at the University of Alabama at Birmingham.
In ENABLE III, 122 caregivers were randomized at the time of the patient’s cancer diagnosis or 12 weeks later to a palliative care intervention that consisted of three weekly structured educational telephone calls from an advanced practice nurse coach, monthly check-in calls to address new or ongoing issues, and a bereavement call for caregivers whose loved ones died.
Caregivers were not restricted to family members, but could include close friends and even neighbors. Their mean age was 60 years, 79% were female, 75% were spouses, and all had at least a high school education.
At 12 weeks from the start of the intervention, caregivers in the immediate versus delayed group had significantly better quality of life on the Caregiver Quality of Life Index–Cancer scale (mean 50.2 vs. 56.1; P = .02) and less depressive symptoms on the Center for Epidemiologic Studies Depression (CESD) scale (10.2 vs. 16.6; P = .0006), Dr. Dionne-Odom said. Notably, the delayed group surpassed the clinical cutoff for depression of 16 on the CESD scale, he added.
The intervention did not appear to change the perception among caregivers of what was demanded of them by the patient or their objective burden, though there was a trend among the immediate group for improved caregiver stress burden on the Montgomery Borgatta Caregiver Burden Scale (13.2 vs. 13.8; P = .10).
There was no significant difference between groups in depression or grief scores for caregivers of decedents. A difference may have been detected with a larger sample size, he said, adding that prior studies have shown that reducing caregiver stress before patients’ death is associated with better bereavement adjustment.
As for why caregivers appear to benefit more than the patients from the parallel palliative care interventions, Dr. Bakitas said in an interview it may be the timing of the assessments, adding that other studies have shown an impact of palliative care at 4 months, but not at 3 months.
AT THE ASCO ANNUAL MEETING 2014
Key clinical point: Palliative care delivered at the time of cancer diagnosis improves survival.
Major finding: The risk of death at 1 year was significantly lower in the immediate palliative care group versus the delayed palliative care group (hazard ratio 0.72; P = .003).
Data source: A randomized trial of palliative oncology care in 207 patients with advanced cancer and their caregivers.
Disclosures: The National Institute for Nursing Research funded the study. Dr. Bakitas reported having no relevant disclosures.
Elderly males with DLBCL require increased rituximab dosing
©ASCO/Phil McCarten
CHICAGO—Elderly males with non-Hodgkin lymphoma (NHL) may require one-third higher doses of rituximab than the current standard to attain optimal responses to rituximab-containing chemotherapy, a new study suggests.
Increasing the rituximab dose eliminated any gender-related differences in survival among elderly patients with aggressive, CD20+, B-cell lymphomas, said investigator Michael Pfreundschuh, MD, of Saarland University Medical Center in Germany.
He presented this finding at the 2014 ASCO Annual Meeting (abstract 8501).
Although rituximab has been used in NHL for nearly 2 decades, standard dosing of the drug is still largely empiric. Only recently have researchers examined whether responses to the drug may vary by gender and age.
New data show that rituximab clears the body more rapidly in elderly males than elderly females, suggesting that rituximab dosing may need to be increased in older men to maintain adequate drug exposure.
Dr Pfreundschuh noted that the RICOVER-60 trial established 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 14 days (R-CHOP-14), followed by 2 additional cycles of rituximab, as the new standard of care for elderly patients with NHL in Germany.
Further analysis of the trial’s results indicates that rituximab dosing may be inadequate in males older than 60, since they fare much worse than elderly females in terms of progression-free survival (PFS).
To test this gender difference, the German High-grade Non-Hodgkin Lymphoma Study Group designed the SEXIE-R-CHOP-14 trial.
The group tested 2 different rituximab doses in patients aged 61 to 80 with stage I to IV, CD20+, diffuse large B-cell lymphoma (DLBCL). A group of 120 females received rituximab at 375 mg/m2 per treatment cycle, and a group of 148 males received 500 mg/m2 per treatment cycle.
The increased rituximab dose in males resulted in slightly higher trough serum levels than in females. However, rituximab levels dropped faster in males, resulting in nearly identical serum levels thereafter and a very similar overall rituximab exposure time, Dr Pfreundschuh said.
The higher dose of rituximab given to elderly males did not result in increased toxicity.
Survival rates were similar between the male and female groups. The 3-year PFS was 74% in males and 68% in females, and 3-year overall survival was 82% in males and 72% in females.
A multivariate analysis that evaluated gender as a risk factor revealed that the male-vs-female hazard ratio for PFS was 0.8 in SEXIE-R-CHOP-14, compared to 1.6 in RICOVER-60. Similarly, the male-vs-female hazard ratio for overall survival was 0.7 in SEXIE-R-CHOP-14 and 1.4 in RICOVER-60.
“Increasing the rituximab dose by one-third eliminated the increased risk [of death and progression in] elderly males,” Dr Pfreundschuh concluded.
He also noted that younger males and females have faster rituximab clearance than elderly females. So increasing the dose in these populations should also result in a better outcome.
©ASCO/Phil McCarten
CHICAGO—Elderly males with non-Hodgkin lymphoma (NHL) may require one-third higher doses of rituximab than the current standard to attain optimal responses to rituximab-containing chemotherapy, a new study suggests.
Increasing the rituximab dose eliminated any gender-related differences in survival among elderly patients with aggressive, CD20+, B-cell lymphomas, said investigator Michael Pfreundschuh, MD, of Saarland University Medical Center in Germany.
He presented this finding at the 2014 ASCO Annual Meeting (abstract 8501).
Although rituximab has been used in NHL for nearly 2 decades, standard dosing of the drug is still largely empiric. Only recently have researchers examined whether responses to the drug may vary by gender and age.
New data show that rituximab clears the body more rapidly in elderly males than elderly females, suggesting that rituximab dosing may need to be increased in older men to maintain adequate drug exposure.
Dr Pfreundschuh noted that the RICOVER-60 trial established 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 14 days (R-CHOP-14), followed by 2 additional cycles of rituximab, as the new standard of care for elderly patients with NHL in Germany.
Further analysis of the trial’s results indicates that rituximab dosing may be inadequate in males older than 60, since they fare much worse than elderly females in terms of progression-free survival (PFS).
To test this gender difference, the German High-grade Non-Hodgkin Lymphoma Study Group designed the SEXIE-R-CHOP-14 trial.
The group tested 2 different rituximab doses in patients aged 61 to 80 with stage I to IV, CD20+, diffuse large B-cell lymphoma (DLBCL). A group of 120 females received rituximab at 375 mg/m2 per treatment cycle, and a group of 148 males received 500 mg/m2 per treatment cycle.
The increased rituximab dose in males resulted in slightly higher trough serum levels than in females. However, rituximab levels dropped faster in males, resulting in nearly identical serum levels thereafter and a very similar overall rituximab exposure time, Dr Pfreundschuh said.
The higher dose of rituximab given to elderly males did not result in increased toxicity.
Survival rates were similar between the male and female groups. The 3-year PFS was 74% in males and 68% in females, and 3-year overall survival was 82% in males and 72% in females.
A multivariate analysis that evaluated gender as a risk factor revealed that the male-vs-female hazard ratio for PFS was 0.8 in SEXIE-R-CHOP-14, compared to 1.6 in RICOVER-60. Similarly, the male-vs-female hazard ratio for overall survival was 0.7 in SEXIE-R-CHOP-14 and 1.4 in RICOVER-60.
“Increasing the rituximab dose by one-third eliminated the increased risk [of death and progression in] elderly males,” Dr Pfreundschuh concluded.
He also noted that younger males and females have faster rituximab clearance than elderly females. So increasing the dose in these populations should also result in a better outcome.
©ASCO/Phil McCarten
CHICAGO—Elderly males with non-Hodgkin lymphoma (NHL) may require one-third higher doses of rituximab than the current standard to attain optimal responses to rituximab-containing chemotherapy, a new study suggests.
Increasing the rituximab dose eliminated any gender-related differences in survival among elderly patients with aggressive, CD20+, B-cell lymphomas, said investigator Michael Pfreundschuh, MD, of Saarland University Medical Center in Germany.
He presented this finding at the 2014 ASCO Annual Meeting (abstract 8501).
Although rituximab has been used in NHL for nearly 2 decades, standard dosing of the drug is still largely empiric. Only recently have researchers examined whether responses to the drug may vary by gender and age.
New data show that rituximab clears the body more rapidly in elderly males than elderly females, suggesting that rituximab dosing may need to be increased in older men to maintain adequate drug exposure.
Dr Pfreundschuh noted that the RICOVER-60 trial established 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 14 days (R-CHOP-14), followed by 2 additional cycles of rituximab, as the new standard of care for elderly patients with NHL in Germany.
Further analysis of the trial’s results indicates that rituximab dosing may be inadequate in males older than 60, since they fare much worse than elderly females in terms of progression-free survival (PFS).
To test this gender difference, the German High-grade Non-Hodgkin Lymphoma Study Group designed the SEXIE-R-CHOP-14 trial.
The group tested 2 different rituximab doses in patients aged 61 to 80 with stage I to IV, CD20+, diffuse large B-cell lymphoma (DLBCL). A group of 120 females received rituximab at 375 mg/m2 per treatment cycle, and a group of 148 males received 500 mg/m2 per treatment cycle.
The increased rituximab dose in males resulted in slightly higher trough serum levels than in females. However, rituximab levels dropped faster in males, resulting in nearly identical serum levels thereafter and a very similar overall rituximab exposure time, Dr Pfreundschuh said.
The higher dose of rituximab given to elderly males did not result in increased toxicity.
Survival rates were similar between the male and female groups. The 3-year PFS was 74% in males and 68% in females, and 3-year overall survival was 82% in males and 72% in females.
A multivariate analysis that evaluated gender as a risk factor revealed that the male-vs-female hazard ratio for PFS was 0.8 in SEXIE-R-CHOP-14, compared to 1.6 in RICOVER-60. Similarly, the male-vs-female hazard ratio for overall survival was 0.7 in SEXIE-R-CHOP-14 and 1.4 in RICOVER-60.
“Increasing the rituximab dose by one-third eliminated the increased risk [of death and progression in] elderly males,” Dr Pfreundschuh concluded.
He also noted that younger males and females have faster rituximab clearance than elderly females. So increasing the dose in these populations should also result in a better outcome.
Switch to nilotinib improves deep molecular response in CML
©ASCO/Phil McCarten
CHICAGO—Patients with chronic myeloid leukemia (CML) are more likely to achieve a deep molecular response if they switch to nilotinib rather than remain on imatinib, updated research suggests.
Patients with detectable disease who crossed over from imatinib to nilotinib after 24 months on the ENESTcmr study were able to achieve deep molecular responses (MR 4.5) by 36 months.
But none of the patients who remained on imatinib achieved undetectable BCR-ABL transcripts.
“Longer follow-up supports switching from imatinib to nilotinib to attain deep molecular responses,” said study investigator Nelson Spector, MD, of Federal University of Rio de Janeiro in Brazil.
“Achievement of deeper molecular responses with nilotinib therapy may increase patient eligibility for treatment-free remission trials.”
Dr Spector presented these results—an update of the ongoing, phase 3 ENESTcmr study—at the 2014 ASCO Annual Meeting (abstract 7025).
The study included 207 patients with Philadelphia-chromosome-positive CML in chronic phase who were treated with imatinib for at least 2 years and achieved complete cytogenetic response but had detectable BCR-ABL transcripts.
With 36 months’ follow-up, rates of MR 4.5 remained higher with nilotinib vs imatinib (47% vs 33%). The median time to achievement of MR 4.5 was 24 months with nilotinib and was not reached with imatinib after the 36-month follow-up.
“Patients experienced a rapid reduction in median BCR-ABL levels within the first 3 months after crossover from imatinib to nilotinib,” Dr Spector said. “No patient with detectable BCR-ABL at 24 months who remained on imatinib achieved this response with another year of follow-up.”
MR 4.5 rates were higher by 12 months in patients randomized to nilotinib (33%) than patients who crossed over from imatinib to nilotinib (21%).
“Three years follow-up shows the ability to achieve undetectable BCR-ABL status with nilotinib as we strive to achieve deep molecular responses with the potential to stop therapy,” said ASCO discussant Michael Mauro, MD, of the Memorial Sloan-Kettering Cancer Center in New York.
However, he questioned whether MR 4.5, “the last, deepest milestone of relevance, is enough to assess stopping.”
By 3 years of follow-up, 93 patients (92.1%) on nilotinib and 72 patients (69.9%) on imatinib had drug-related adverse events.
The most common events with nilotinib were headache, rash, and pruritus. With imatinib, the most common events were muscle spasms, nausea, and diarrhea. More cardiovascular events were reported in patients randomized to nilotinib compared with imatinib.
“Nilotinib-treated patients experienced adverse events early after switching from long-term imatinib therapy,” Dr Spector said. “These adverse events were expected and consistent with the safety profile of nilotinib observed in other studies.”
©ASCO/Phil McCarten
CHICAGO—Patients with chronic myeloid leukemia (CML) are more likely to achieve a deep molecular response if they switch to nilotinib rather than remain on imatinib, updated research suggests.
Patients with detectable disease who crossed over from imatinib to nilotinib after 24 months on the ENESTcmr study were able to achieve deep molecular responses (MR 4.5) by 36 months.
But none of the patients who remained on imatinib achieved undetectable BCR-ABL transcripts.
“Longer follow-up supports switching from imatinib to nilotinib to attain deep molecular responses,” said study investigator Nelson Spector, MD, of Federal University of Rio de Janeiro in Brazil.
“Achievement of deeper molecular responses with nilotinib therapy may increase patient eligibility for treatment-free remission trials.”
Dr Spector presented these results—an update of the ongoing, phase 3 ENESTcmr study—at the 2014 ASCO Annual Meeting (abstract 7025).
The study included 207 patients with Philadelphia-chromosome-positive CML in chronic phase who were treated with imatinib for at least 2 years and achieved complete cytogenetic response but had detectable BCR-ABL transcripts.
With 36 months’ follow-up, rates of MR 4.5 remained higher with nilotinib vs imatinib (47% vs 33%). The median time to achievement of MR 4.5 was 24 months with nilotinib and was not reached with imatinib after the 36-month follow-up.
“Patients experienced a rapid reduction in median BCR-ABL levels within the first 3 months after crossover from imatinib to nilotinib,” Dr Spector said. “No patient with detectable BCR-ABL at 24 months who remained on imatinib achieved this response with another year of follow-up.”
MR 4.5 rates were higher by 12 months in patients randomized to nilotinib (33%) than patients who crossed over from imatinib to nilotinib (21%).
“Three years follow-up shows the ability to achieve undetectable BCR-ABL status with nilotinib as we strive to achieve deep molecular responses with the potential to stop therapy,” said ASCO discussant Michael Mauro, MD, of the Memorial Sloan-Kettering Cancer Center in New York.
However, he questioned whether MR 4.5, “the last, deepest milestone of relevance, is enough to assess stopping.”
By 3 years of follow-up, 93 patients (92.1%) on nilotinib and 72 patients (69.9%) on imatinib had drug-related adverse events.
The most common events with nilotinib were headache, rash, and pruritus. With imatinib, the most common events were muscle spasms, nausea, and diarrhea. More cardiovascular events were reported in patients randomized to nilotinib compared with imatinib.
“Nilotinib-treated patients experienced adverse events early after switching from long-term imatinib therapy,” Dr Spector said. “These adverse events were expected and consistent with the safety profile of nilotinib observed in other studies.”
©ASCO/Phil McCarten
CHICAGO—Patients with chronic myeloid leukemia (CML) are more likely to achieve a deep molecular response if they switch to nilotinib rather than remain on imatinib, updated research suggests.
Patients with detectable disease who crossed over from imatinib to nilotinib after 24 months on the ENESTcmr study were able to achieve deep molecular responses (MR 4.5) by 36 months.
But none of the patients who remained on imatinib achieved undetectable BCR-ABL transcripts.
“Longer follow-up supports switching from imatinib to nilotinib to attain deep molecular responses,” said study investigator Nelson Spector, MD, of Federal University of Rio de Janeiro in Brazil.
“Achievement of deeper molecular responses with nilotinib therapy may increase patient eligibility for treatment-free remission trials.”
Dr Spector presented these results—an update of the ongoing, phase 3 ENESTcmr study—at the 2014 ASCO Annual Meeting (abstract 7025).
The study included 207 patients with Philadelphia-chromosome-positive CML in chronic phase who were treated with imatinib for at least 2 years and achieved complete cytogenetic response but had detectable BCR-ABL transcripts.
With 36 months’ follow-up, rates of MR 4.5 remained higher with nilotinib vs imatinib (47% vs 33%). The median time to achievement of MR 4.5 was 24 months with nilotinib and was not reached with imatinib after the 36-month follow-up.
“Patients experienced a rapid reduction in median BCR-ABL levels within the first 3 months after crossover from imatinib to nilotinib,” Dr Spector said. “No patient with detectable BCR-ABL at 24 months who remained on imatinib achieved this response with another year of follow-up.”
MR 4.5 rates were higher by 12 months in patients randomized to nilotinib (33%) than patients who crossed over from imatinib to nilotinib (21%).
“Three years follow-up shows the ability to achieve undetectable BCR-ABL status with nilotinib as we strive to achieve deep molecular responses with the potential to stop therapy,” said ASCO discussant Michael Mauro, MD, of the Memorial Sloan-Kettering Cancer Center in New York.
However, he questioned whether MR 4.5, “the last, deepest milestone of relevance, is enough to assess stopping.”
By 3 years of follow-up, 93 patients (92.1%) on nilotinib and 72 patients (69.9%) on imatinib had drug-related adverse events.
The most common events with nilotinib were headache, rash, and pruritus. With imatinib, the most common events were muscle spasms, nausea, and diarrhea. More cardiovascular events were reported in patients randomized to nilotinib compared with imatinib.
“Nilotinib-treated patients experienced adverse events early after switching from long-term imatinib therapy,” Dr Spector said. “These adverse events were expected and consistent with the safety profile of nilotinib observed in other studies.”
ALTTO: Dual HER2 blockade offers no survival edge in adjuvant breast cancer treatment
CHICAGO – Dual HER2 blockade with lapatinib and trastuzumab provides no additional benefit in the adjuvant treatment of HER2-positive breast cancer, according to the long-awaited, first results from the phase III ALTTO trial.
At 4 years, the primary outcome of disease-free survival was 86% with trastuzumab alone, compared with 88% with concurrent lapatinib (Tykerb) and trastuzumab (Herceptin) (hazard ratio, 0.84; P = .048), and 87% with trastuzumab followed by lapatinib (HR, 0.96; P = .610), Dr. Martine Piccart-Gebhart reported during the plenary session at the annual meeting of the American Society of Clinical Oncology.
Median overall survival rates were 94%, 95%, and 95%, respectively.
ALTTO’s sister trial, NeoALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization), demonstrated that neoadjuvant treatment with combination trastuzumab and lapatinib doubled the number of pathological complete responses (pCRs), compared with each single agent, and reduced the overall risk of death by two-thirds in women with a pCR.
"The doubling in pCR observed in NeoALTTO did not translate into improved survival outcomes in ALTTO at 4.5 years," said Dr. Piccart-Gebhart, head of the medicine department, Jules Bordet Institute, Brussels.
Invited discussant and past ASCO president Dr. George Sledge Jr., professor of medicine and chief of oncology at Stanford University Medical Center, Palo Alto, Calif., pointed out that ALTTO called for a stringent P value of .025 or less to demonstrate statistical significance, but that no one should be "fooled" by the disease-free survival P value of .048 into thinking this was a positive trial.
"This is a negative trial," he said.
He also noted that the 555 disease-free events seen in ALTTO fell far short of the 850 events planned for, and thus the trial was underpowered.
"Might this trial, with more events and further follow-up, turn statistically positive? Perhaps, but not very positive given the results we’ve seen today," Dr. Sledge commented. "HER2 has reverted to the incrementalism that we see so commonly in the adjuvant field. This is not, alas, 2005. This is not a great leap forward. This is a serious disappointment not just for investigators, but for the entire field."
Several previous trials (B-31, N9831, and HERA) presented at the same meeting in 2005 showed a striking disease-free survival advantage from the addition of 1 year of trastuzumab to adjuvant chemotherapy in women with HER2-positive breast cancer.
During a press briefing, ALTTO study cochair Dr. Edith Perez cast the low event rate of ALTTO in a slightly more positive light, saying that the "patients overall did pretty well."
Ripple effects
Had the results of ALTTO been positive, it would have changed the design of future breast cancer trials by eliminating the need for large adjuvant trials, suggested Dr. Perez, deputy director at large, Mayo Clinic Cancer Center, Jacksonville, Fla. Novel targeted agents could have been reliably evaluated in the neoadjuvant setting if pCR had correlated with the findings in adjuvant trials.
As it stands now, the data call into question whether an improvement in pCR can be routinely used as a reliable surrogate for disease-free and overall survival, ASCO president Dr. Clifford Hudis, chief of breast cancer at Memorial Sloan Kettering Cancer Center, New York, said at the briefing.
"The answer from ALTTO right now is maybe not, and this, I think, is going to cause a tremendous amount of high-level technical scientific discussion in terms of drug development," he told reporters.
Dr. Hudis pointed out that last fall, the Food and Drug Administration for the first time ever approved a drug, pertuzumab (Perjeta), for use in the preoperative breast cancer setting based on an increased pCR rate alone. The hope is that this will ultimately save lives, although this question won’t be answered until 2016, when results from the APHINITY trial are expected, he said.
Based on the ALTTO data, "the simple link that improving the rate of shrinkage of the cancer will necessarily reduce the rate of distant recurrence is not established," Dr. Hudis said. "So our ability to go from big studies taking many years to small studies taking months is not established. That’s a fundamental observation, and it may have implications well beyond breast cancer."
ALTTO design
The open-label, multicenter ALTTO study randomized 8,381 women after surgery to concurrent trastuzumab and lapatinib, trastuzumab followed by lapatinib, or trastuzumab alone for 1 year. Patients received anti-HER2 therapy after completing all chemotherapy (design 1), concurrently with a taxane following anthracycline (design 2), or concurrently with a non-anthracycline, platinum-containing regimen (design 2B).
The lapatinib-alone vs. trastuzumab-alone arm was closed in early 2011 due to futility, and results from that arm will be presented later this year.
The current efficacy results were based on 6,281 women, with 4,613 receiving the anti-HER2 drugs after completing chemotherapy.
Lapatinib was associated with significant increases in diarrhea, hepatobiliary events, and skin rash or erythema. This may explain why only 60-78% of patients in the lapatinib-containing arms received at least 85% of protocol-specified dose, Dr. Piccart-Gebhart said during the formal presentation of the late-breaking abstract.
Importantly, cardiac toxicity was "remarkably low in all treatment arms" at less than 1%, she said. This was true despite 97% of women receiving anthracyclines.
A primary cardiac event, defined as cardiac death or severe congestive heart failure (New York Heart Association class III-IV), occurred in 0.97% of patients on lapatinib plus trastuzumab, 0.25% on trastuzumab followed by lapatinib, and 0.86% on trastuzumab alone. Any cardiac event was reported in 3.7%, 2.4%, and 4.5%, respectively.
Follow-up in ALTTO will continue, with a protocol-specified updated efficacy analysis planned in 2 years.
ALTTO was sponsored by the National Cancer Institute and GlaxoSmithKline, maker of lapatinib. Dr. Piccart-Gebhart reported employment or a leadership role with PharmaMar, and a consulting/advisory role and honoraria from several companies, but not GSK. Dr. Sledge reported serving as a board member for Syndax and as a consultant for Roche-Genentech, Symphogen, and Seattle Genetics. Dr. Perez reported having no financial disclosures.
CHICAGO – Dual HER2 blockade with lapatinib and trastuzumab provides no additional benefit in the adjuvant treatment of HER2-positive breast cancer, according to the long-awaited, first results from the phase III ALTTO trial.
At 4 years, the primary outcome of disease-free survival was 86% with trastuzumab alone, compared with 88% with concurrent lapatinib (Tykerb) and trastuzumab (Herceptin) (hazard ratio, 0.84; P = .048), and 87% with trastuzumab followed by lapatinib (HR, 0.96; P = .610), Dr. Martine Piccart-Gebhart reported during the plenary session at the annual meeting of the American Society of Clinical Oncology.
Median overall survival rates were 94%, 95%, and 95%, respectively.
ALTTO’s sister trial, NeoALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization), demonstrated that neoadjuvant treatment with combination trastuzumab and lapatinib doubled the number of pathological complete responses (pCRs), compared with each single agent, and reduced the overall risk of death by two-thirds in women with a pCR.
"The doubling in pCR observed in NeoALTTO did not translate into improved survival outcomes in ALTTO at 4.5 years," said Dr. Piccart-Gebhart, head of the medicine department, Jules Bordet Institute, Brussels.
Invited discussant and past ASCO president Dr. George Sledge Jr., professor of medicine and chief of oncology at Stanford University Medical Center, Palo Alto, Calif., pointed out that ALTTO called for a stringent P value of .025 or less to demonstrate statistical significance, but that no one should be "fooled" by the disease-free survival P value of .048 into thinking this was a positive trial.
"This is a negative trial," he said.
He also noted that the 555 disease-free events seen in ALTTO fell far short of the 850 events planned for, and thus the trial was underpowered.
"Might this trial, with more events and further follow-up, turn statistically positive? Perhaps, but not very positive given the results we’ve seen today," Dr. Sledge commented. "HER2 has reverted to the incrementalism that we see so commonly in the adjuvant field. This is not, alas, 2005. This is not a great leap forward. This is a serious disappointment not just for investigators, but for the entire field."
Several previous trials (B-31, N9831, and HERA) presented at the same meeting in 2005 showed a striking disease-free survival advantage from the addition of 1 year of trastuzumab to adjuvant chemotherapy in women with HER2-positive breast cancer.
During a press briefing, ALTTO study cochair Dr. Edith Perez cast the low event rate of ALTTO in a slightly more positive light, saying that the "patients overall did pretty well."
Ripple effects
Had the results of ALTTO been positive, it would have changed the design of future breast cancer trials by eliminating the need for large adjuvant trials, suggested Dr. Perez, deputy director at large, Mayo Clinic Cancer Center, Jacksonville, Fla. Novel targeted agents could have been reliably evaluated in the neoadjuvant setting if pCR had correlated with the findings in adjuvant trials.
As it stands now, the data call into question whether an improvement in pCR can be routinely used as a reliable surrogate for disease-free and overall survival, ASCO president Dr. Clifford Hudis, chief of breast cancer at Memorial Sloan Kettering Cancer Center, New York, said at the briefing.
"The answer from ALTTO right now is maybe not, and this, I think, is going to cause a tremendous amount of high-level technical scientific discussion in terms of drug development," he told reporters.
Dr. Hudis pointed out that last fall, the Food and Drug Administration for the first time ever approved a drug, pertuzumab (Perjeta), for use in the preoperative breast cancer setting based on an increased pCR rate alone. The hope is that this will ultimately save lives, although this question won’t be answered until 2016, when results from the APHINITY trial are expected, he said.
Based on the ALTTO data, "the simple link that improving the rate of shrinkage of the cancer will necessarily reduce the rate of distant recurrence is not established," Dr. Hudis said. "So our ability to go from big studies taking many years to small studies taking months is not established. That’s a fundamental observation, and it may have implications well beyond breast cancer."
ALTTO design
The open-label, multicenter ALTTO study randomized 8,381 women after surgery to concurrent trastuzumab and lapatinib, trastuzumab followed by lapatinib, or trastuzumab alone for 1 year. Patients received anti-HER2 therapy after completing all chemotherapy (design 1), concurrently with a taxane following anthracycline (design 2), or concurrently with a non-anthracycline, platinum-containing regimen (design 2B).
The lapatinib-alone vs. trastuzumab-alone arm was closed in early 2011 due to futility, and results from that arm will be presented later this year.
The current efficacy results were based on 6,281 women, with 4,613 receiving the anti-HER2 drugs after completing chemotherapy.
Lapatinib was associated with significant increases in diarrhea, hepatobiliary events, and skin rash or erythema. This may explain why only 60-78% of patients in the lapatinib-containing arms received at least 85% of protocol-specified dose, Dr. Piccart-Gebhart said during the formal presentation of the late-breaking abstract.
Importantly, cardiac toxicity was "remarkably low in all treatment arms" at less than 1%, she said. This was true despite 97% of women receiving anthracyclines.
A primary cardiac event, defined as cardiac death or severe congestive heart failure (New York Heart Association class III-IV), occurred in 0.97% of patients on lapatinib plus trastuzumab, 0.25% on trastuzumab followed by lapatinib, and 0.86% on trastuzumab alone. Any cardiac event was reported in 3.7%, 2.4%, and 4.5%, respectively.
Follow-up in ALTTO will continue, with a protocol-specified updated efficacy analysis planned in 2 years.
ALTTO was sponsored by the National Cancer Institute and GlaxoSmithKline, maker of lapatinib. Dr. Piccart-Gebhart reported employment or a leadership role with PharmaMar, and a consulting/advisory role and honoraria from several companies, but not GSK. Dr. Sledge reported serving as a board member for Syndax and as a consultant for Roche-Genentech, Symphogen, and Seattle Genetics. Dr. Perez reported having no financial disclosures.
CHICAGO – Dual HER2 blockade with lapatinib and trastuzumab provides no additional benefit in the adjuvant treatment of HER2-positive breast cancer, according to the long-awaited, first results from the phase III ALTTO trial.
At 4 years, the primary outcome of disease-free survival was 86% with trastuzumab alone, compared with 88% with concurrent lapatinib (Tykerb) and trastuzumab (Herceptin) (hazard ratio, 0.84; P = .048), and 87% with trastuzumab followed by lapatinib (HR, 0.96; P = .610), Dr. Martine Piccart-Gebhart reported during the plenary session at the annual meeting of the American Society of Clinical Oncology.
Median overall survival rates were 94%, 95%, and 95%, respectively.
ALTTO’s sister trial, NeoALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization), demonstrated that neoadjuvant treatment with combination trastuzumab and lapatinib doubled the number of pathological complete responses (pCRs), compared with each single agent, and reduced the overall risk of death by two-thirds in women with a pCR.
"The doubling in pCR observed in NeoALTTO did not translate into improved survival outcomes in ALTTO at 4.5 years," said Dr. Piccart-Gebhart, head of the medicine department, Jules Bordet Institute, Brussels.
Invited discussant and past ASCO president Dr. George Sledge Jr., professor of medicine and chief of oncology at Stanford University Medical Center, Palo Alto, Calif., pointed out that ALTTO called for a stringent P value of .025 or less to demonstrate statistical significance, but that no one should be "fooled" by the disease-free survival P value of .048 into thinking this was a positive trial.
"This is a negative trial," he said.
He also noted that the 555 disease-free events seen in ALTTO fell far short of the 850 events planned for, and thus the trial was underpowered.
"Might this trial, with more events and further follow-up, turn statistically positive? Perhaps, but not very positive given the results we’ve seen today," Dr. Sledge commented. "HER2 has reverted to the incrementalism that we see so commonly in the adjuvant field. This is not, alas, 2005. This is not a great leap forward. This is a serious disappointment not just for investigators, but for the entire field."
Several previous trials (B-31, N9831, and HERA) presented at the same meeting in 2005 showed a striking disease-free survival advantage from the addition of 1 year of trastuzumab to adjuvant chemotherapy in women with HER2-positive breast cancer.
During a press briefing, ALTTO study cochair Dr. Edith Perez cast the low event rate of ALTTO in a slightly more positive light, saying that the "patients overall did pretty well."
Ripple effects
Had the results of ALTTO been positive, it would have changed the design of future breast cancer trials by eliminating the need for large adjuvant trials, suggested Dr. Perez, deputy director at large, Mayo Clinic Cancer Center, Jacksonville, Fla. Novel targeted agents could have been reliably evaluated in the neoadjuvant setting if pCR had correlated with the findings in adjuvant trials.
As it stands now, the data call into question whether an improvement in pCR can be routinely used as a reliable surrogate for disease-free and overall survival, ASCO president Dr. Clifford Hudis, chief of breast cancer at Memorial Sloan Kettering Cancer Center, New York, said at the briefing.
"The answer from ALTTO right now is maybe not, and this, I think, is going to cause a tremendous amount of high-level technical scientific discussion in terms of drug development," he told reporters.
Dr. Hudis pointed out that last fall, the Food and Drug Administration for the first time ever approved a drug, pertuzumab (Perjeta), for use in the preoperative breast cancer setting based on an increased pCR rate alone. The hope is that this will ultimately save lives, although this question won’t be answered until 2016, when results from the APHINITY trial are expected, he said.
Based on the ALTTO data, "the simple link that improving the rate of shrinkage of the cancer will necessarily reduce the rate of distant recurrence is not established," Dr. Hudis said. "So our ability to go from big studies taking many years to small studies taking months is not established. That’s a fundamental observation, and it may have implications well beyond breast cancer."
ALTTO design
The open-label, multicenter ALTTO study randomized 8,381 women after surgery to concurrent trastuzumab and lapatinib, trastuzumab followed by lapatinib, or trastuzumab alone for 1 year. Patients received anti-HER2 therapy after completing all chemotherapy (design 1), concurrently with a taxane following anthracycline (design 2), or concurrently with a non-anthracycline, platinum-containing regimen (design 2B).
The lapatinib-alone vs. trastuzumab-alone arm was closed in early 2011 due to futility, and results from that arm will be presented later this year.
The current efficacy results were based on 6,281 women, with 4,613 receiving the anti-HER2 drugs after completing chemotherapy.
Lapatinib was associated with significant increases in diarrhea, hepatobiliary events, and skin rash or erythema. This may explain why only 60-78% of patients in the lapatinib-containing arms received at least 85% of protocol-specified dose, Dr. Piccart-Gebhart said during the formal presentation of the late-breaking abstract.
Importantly, cardiac toxicity was "remarkably low in all treatment arms" at less than 1%, she said. This was true despite 97% of women receiving anthracyclines.
A primary cardiac event, defined as cardiac death or severe congestive heart failure (New York Heart Association class III-IV), occurred in 0.97% of patients on lapatinib plus trastuzumab, 0.25% on trastuzumab followed by lapatinib, and 0.86% on trastuzumab alone. Any cardiac event was reported in 3.7%, 2.4%, and 4.5%, respectively.
Follow-up in ALTTO will continue, with a protocol-specified updated efficacy analysis planned in 2 years.
ALTTO was sponsored by the National Cancer Institute and GlaxoSmithKline, maker of lapatinib. Dr. Piccart-Gebhart reported employment or a leadership role with PharmaMar, and a consulting/advisory role and honoraria from several companies, but not GSK. Dr. Sledge reported serving as a board member for Syndax and as a consultant for Roche-Genentech, Symphogen, and Seattle Genetics. Dr. Perez reported having no financial disclosures.
AT THE ASCO ANNUAL MEETING 2014
Major finding: Disease-free survival at 4 years was 86% with trastuzumab, 88% with concurrent lapatinib plus trastuzumab, and 87% with trastuzumab followed by lapatinib.
Data source: A randomized phase III study in 8,381 women with HER2-positive breast cancer.
Key clinical point: Combination lapatinib and trastuzumab does not improve DFS or OS in adjuvant HER2-positive early breast cancer.
Disclosures: ALTTO was sponsored by the National Cancer Institute and GlaxoSmithKline, maker of lapatinib. Dr. Piccart-Gebhart reported employment or a leadership role with PharmaMar and a consulting/advisory role and honoraria from several companies, but not GSK. Dr. Perez reported having no financial disclosures.
CNS involvement predicts relapse but not survival in ARL, study shows
CHICAGO—Investigators have found evidence to suggest that identifying central nervous system (CNS) involvement at diagnosis does not impact overall survival for patients with AIDS-related lymphoma (ARL).
The research showed that ARL patients with CNS involvement at diagnosis were nearly 3 times as likely as their peers to have CNS relapse during cancer treatment.
But there was no significant difference between the 2 groups with regard to survival.
This may be due to the low overall incidence of CNS relapse, the use of insufficient treatments, and/or inadequate methods for identifying patients with CNS involvement, according to the investigators.
Stefan K. Barta, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, and his colleagues conducted this research and presented the results at the 2014 ASCO Annual Meeting (abstract 8570).
In 2013, Dr Barta led the assembly of a database containing medical data from more than 1500 patients newly diagnosed with ARL who participated in clinical trials in Europe and the US from 1990 through 2010.
In the new study, he and his colleagues used the database to identify 880 patients with ARL whose data included complete information on CNS involvement at diagnosis and CNS relapse.
The team set out to find associations between CNS relapse and patient characteristics, including age, sex, CD4 count, lymphoma subtype, treatment history with combination antiretroviral therapies (cART), rituximab use, and the type of initial chemotherapy.
All of the patients had received either intrathecal therapy for CNS involvement or intrathecal prophylaxis with single-agent or 3-agent regimens. Sixty-nine percent of patients (n=607) had received cART, and 31% (n=276) had received rituximab-containing induction chemoimmunotherapy.
CNS involvement was identified in 13% of patients at diagnosis, including 27% of patients with Burkitt lymphoma or Burkitt-like lymphoma and 6% of patients with diffuse large B-cell lymphoma.
There was no difference in the prevalence of baseline CNS involvement between patients treated before and after the introduction of cART (13% each).
In all, 5.3% of patients experienced CNS relapse at a median of 4.2 months after diagnosis (range, 0.3-19.3 months). This included 12% of patients diagnosed with CNS involvement at baseline and 4% of patients who were not.
The median overall survival after CNS relapse was 1.6 months (range, 0-86.4 months). There was no significant difference in overall survival between patients with CNS involvement at diagnosis and those without it. The hazard ratio was 0.85 (P=0.32).
Multivariate analysis showed the only baseline characteristic significantly associated with the frequency of CNS relapse was CNS involvement, with a hazard ratio of 2.9 (P=0.01). None of the treatments had a significant impact on CNS relapse.
Dr Barta said these results suggest that current treatments are insufficient, and the approaches used to identify CNS involvement may be missing many patients who are at risk of CNS relapse.
“A lot of patients who relapsed probably had undetected CNS involvement at diagnosis,” he said. “We want to figure out if there are better strategies to identify patients at risk.”
CHICAGO—Investigators have found evidence to suggest that identifying central nervous system (CNS) involvement at diagnosis does not impact overall survival for patients with AIDS-related lymphoma (ARL).
The research showed that ARL patients with CNS involvement at diagnosis were nearly 3 times as likely as their peers to have CNS relapse during cancer treatment.
But there was no significant difference between the 2 groups with regard to survival.
This may be due to the low overall incidence of CNS relapse, the use of insufficient treatments, and/or inadequate methods for identifying patients with CNS involvement, according to the investigators.
Stefan K. Barta, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, and his colleagues conducted this research and presented the results at the 2014 ASCO Annual Meeting (abstract 8570).
In 2013, Dr Barta led the assembly of a database containing medical data from more than 1500 patients newly diagnosed with ARL who participated in clinical trials in Europe and the US from 1990 through 2010.
In the new study, he and his colleagues used the database to identify 880 patients with ARL whose data included complete information on CNS involvement at diagnosis and CNS relapse.
The team set out to find associations between CNS relapse and patient characteristics, including age, sex, CD4 count, lymphoma subtype, treatment history with combination antiretroviral therapies (cART), rituximab use, and the type of initial chemotherapy.
All of the patients had received either intrathecal therapy for CNS involvement or intrathecal prophylaxis with single-agent or 3-agent regimens. Sixty-nine percent of patients (n=607) had received cART, and 31% (n=276) had received rituximab-containing induction chemoimmunotherapy.
CNS involvement was identified in 13% of patients at diagnosis, including 27% of patients with Burkitt lymphoma or Burkitt-like lymphoma and 6% of patients with diffuse large B-cell lymphoma.
There was no difference in the prevalence of baseline CNS involvement between patients treated before and after the introduction of cART (13% each).
In all, 5.3% of patients experienced CNS relapse at a median of 4.2 months after diagnosis (range, 0.3-19.3 months). This included 12% of patients diagnosed with CNS involvement at baseline and 4% of patients who were not.
The median overall survival after CNS relapse was 1.6 months (range, 0-86.4 months). There was no significant difference in overall survival between patients with CNS involvement at diagnosis and those without it. The hazard ratio was 0.85 (P=0.32).
Multivariate analysis showed the only baseline characteristic significantly associated with the frequency of CNS relapse was CNS involvement, with a hazard ratio of 2.9 (P=0.01). None of the treatments had a significant impact on CNS relapse.
Dr Barta said these results suggest that current treatments are insufficient, and the approaches used to identify CNS involvement may be missing many patients who are at risk of CNS relapse.
“A lot of patients who relapsed probably had undetected CNS involvement at diagnosis,” he said. “We want to figure out if there are better strategies to identify patients at risk.”
CHICAGO—Investigators have found evidence to suggest that identifying central nervous system (CNS) involvement at diagnosis does not impact overall survival for patients with AIDS-related lymphoma (ARL).
The research showed that ARL patients with CNS involvement at diagnosis were nearly 3 times as likely as their peers to have CNS relapse during cancer treatment.
But there was no significant difference between the 2 groups with regard to survival.
This may be due to the low overall incidence of CNS relapse, the use of insufficient treatments, and/or inadequate methods for identifying patients with CNS involvement, according to the investigators.
Stefan K. Barta, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, and his colleagues conducted this research and presented the results at the 2014 ASCO Annual Meeting (abstract 8570).
In 2013, Dr Barta led the assembly of a database containing medical data from more than 1500 patients newly diagnosed with ARL who participated in clinical trials in Europe and the US from 1990 through 2010.
In the new study, he and his colleagues used the database to identify 880 patients with ARL whose data included complete information on CNS involvement at diagnosis and CNS relapse.
The team set out to find associations between CNS relapse and patient characteristics, including age, sex, CD4 count, lymphoma subtype, treatment history with combination antiretroviral therapies (cART), rituximab use, and the type of initial chemotherapy.
All of the patients had received either intrathecal therapy for CNS involvement or intrathecal prophylaxis with single-agent or 3-agent regimens. Sixty-nine percent of patients (n=607) had received cART, and 31% (n=276) had received rituximab-containing induction chemoimmunotherapy.
CNS involvement was identified in 13% of patients at diagnosis, including 27% of patients with Burkitt lymphoma or Burkitt-like lymphoma and 6% of patients with diffuse large B-cell lymphoma.
There was no difference in the prevalence of baseline CNS involvement between patients treated before and after the introduction of cART (13% each).
In all, 5.3% of patients experienced CNS relapse at a median of 4.2 months after diagnosis (range, 0.3-19.3 months). This included 12% of patients diagnosed with CNS involvement at baseline and 4% of patients who were not.
The median overall survival after CNS relapse was 1.6 months (range, 0-86.4 months). There was no significant difference in overall survival between patients with CNS involvement at diagnosis and those without it. The hazard ratio was 0.85 (P=0.32).
Multivariate analysis showed the only baseline characteristic significantly associated with the frequency of CNS relapse was CNS involvement, with a hazard ratio of 2.9 (P=0.01). None of the treatments had a significant impact on CNS relapse.
Dr Barta said these results suggest that current treatments are insufficient, and the approaches used to identify CNS involvement may be missing many patients who are at risk of CNS relapse.
“A lot of patients who relapsed probably had undetected CNS involvement at diagnosis,” he said. “We want to figure out if there are better strategies to identify patients at risk.”
Imatinib appears safe, effective for the long haul
CHICAGO – After a decade on therapy with imatinib, a majority of patients with chronic myeloid leukemia will experience an adverse drug reaction, but most reactions are mild and manageable, according to results from a study presented at the annual meeting of the American Society of Clinical Oncology.
Of 1,375 patients with CML who received imatinib (Gleevec) monotherapy at some point, 1,018 (74%) had nonhematologic toxicities sometime during therapy, but only 199 (14%) had grade 3 or 4 toxicities, and there were no deaths attributed to imatinib, reported Dr. Rüdiger Hehlmann of the University of Heidelberg, Germany, and his colleagues.
Adverse drug reactions were manageable even when imatinib was combined with interferon-alfa (IFN-alfa), the investigators from the German CML Study Group reported in a poster at the meeting.
"After 10 years, imatinib continues to be an excellent choice for most patients with CML," they wrote.
In the 13 years that have elapsed since imatinib was approved in the United States as the first-in-class tyrosine kinase inhibitor, second-generation TKIs and other targeted agents have emerged, drawing attention to the safety of the older regimen.
The investigators evaluated long-term follow-up data and analyzed adverse drug reaction data for 1,501 patients treated with imatinib monotherapy in doses of 400 or 800 mg/day, as well as imatinib 400 mg in combination with IFN-alfa.
At the most recent evaluation, in November 2013, 164 patients had died, 1,003 were still on imatinib, 275 had been switched to a second-generation TKI, and 106 underwent bone marrow transplant (some patients received more than one therapy, accounting for the difference in total numbers).
The median follow-up time was 6.5 years, with some patients on study for as long as 11.5 years.
The probability of 10-year survival was 84%, and of 10-year progression-free survival was 81%.
An analysis of survival by molecular response rates showed an overall survival rate of 89% for those who achieved a major molecular response (MR, defined as a BCR-ABL RNA level of 0.1% or less), and 74% for those who achieved MR 4.5 (a 4.5 log10reduction or greater in BCR-ABL transcripts).
The 8-year probabilities for all grades of adverse events among the patients who received imatinib monotherapy were 41% for edema or fluid overload, 38% for gastrointestinal toxicities, 25% for myalgia/arthralgia, 20% for rash, 17% for musculoskeletal events, 17% for fatigue, 11% for neurological toxicities, and 10% for flulike symptoms.
Five patients had grade 2 or 3 peripheral arterial occlusive disease, but it was not clear whether these events were associated with imatinib.
For most patients the first adverse drug reaction occurred within 3 years of starting on imatinib, with the frequency of reactions decreasing thereafter.
Dr. Hehlmann disclosed receiving research support from Novartis, marketer of imatinib.
CHICAGO – After a decade on therapy with imatinib, a majority of patients with chronic myeloid leukemia will experience an adverse drug reaction, but most reactions are mild and manageable, according to results from a study presented at the annual meeting of the American Society of Clinical Oncology.
Of 1,375 patients with CML who received imatinib (Gleevec) monotherapy at some point, 1,018 (74%) had nonhematologic toxicities sometime during therapy, but only 199 (14%) had grade 3 or 4 toxicities, and there were no deaths attributed to imatinib, reported Dr. Rüdiger Hehlmann of the University of Heidelberg, Germany, and his colleagues.
Adverse drug reactions were manageable even when imatinib was combined with interferon-alfa (IFN-alfa), the investigators from the German CML Study Group reported in a poster at the meeting.
"After 10 years, imatinib continues to be an excellent choice for most patients with CML," they wrote.
In the 13 years that have elapsed since imatinib was approved in the United States as the first-in-class tyrosine kinase inhibitor, second-generation TKIs and other targeted agents have emerged, drawing attention to the safety of the older regimen.
The investigators evaluated long-term follow-up data and analyzed adverse drug reaction data for 1,501 patients treated with imatinib monotherapy in doses of 400 or 800 mg/day, as well as imatinib 400 mg in combination with IFN-alfa.
At the most recent evaluation, in November 2013, 164 patients had died, 1,003 were still on imatinib, 275 had been switched to a second-generation TKI, and 106 underwent bone marrow transplant (some patients received more than one therapy, accounting for the difference in total numbers).
The median follow-up time was 6.5 years, with some patients on study for as long as 11.5 years.
The probability of 10-year survival was 84%, and of 10-year progression-free survival was 81%.
An analysis of survival by molecular response rates showed an overall survival rate of 89% for those who achieved a major molecular response (MR, defined as a BCR-ABL RNA level of 0.1% or less), and 74% for those who achieved MR 4.5 (a 4.5 log10reduction or greater in BCR-ABL transcripts).
The 8-year probabilities for all grades of adverse events among the patients who received imatinib monotherapy were 41% for edema or fluid overload, 38% for gastrointestinal toxicities, 25% for myalgia/arthralgia, 20% for rash, 17% for musculoskeletal events, 17% for fatigue, 11% for neurological toxicities, and 10% for flulike symptoms.
Five patients had grade 2 or 3 peripheral arterial occlusive disease, but it was not clear whether these events were associated with imatinib.
For most patients the first adverse drug reaction occurred within 3 years of starting on imatinib, with the frequency of reactions decreasing thereafter.
Dr. Hehlmann disclosed receiving research support from Novartis, marketer of imatinib.
CHICAGO – After a decade on therapy with imatinib, a majority of patients with chronic myeloid leukemia will experience an adverse drug reaction, but most reactions are mild and manageable, according to results from a study presented at the annual meeting of the American Society of Clinical Oncology.
Of 1,375 patients with CML who received imatinib (Gleevec) monotherapy at some point, 1,018 (74%) had nonhematologic toxicities sometime during therapy, but only 199 (14%) had grade 3 or 4 toxicities, and there were no deaths attributed to imatinib, reported Dr. Rüdiger Hehlmann of the University of Heidelberg, Germany, and his colleagues.
Adverse drug reactions were manageable even when imatinib was combined with interferon-alfa (IFN-alfa), the investigators from the German CML Study Group reported in a poster at the meeting.
"After 10 years, imatinib continues to be an excellent choice for most patients with CML," they wrote.
In the 13 years that have elapsed since imatinib was approved in the United States as the first-in-class tyrosine kinase inhibitor, second-generation TKIs and other targeted agents have emerged, drawing attention to the safety of the older regimen.
The investigators evaluated long-term follow-up data and analyzed adverse drug reaction data for 1,501 patients treated with imatinib monotherapy in doses of 400 or 800 mg/day, as well as imatinib 400 mg in combination with IFN-alfa.
At the most recent evaluation, in November 2013, 164 patients had died, 1,003 were still on imatinib, 275 had been switched to a second-generation TKI, and 106 underwent bone marrow transplant (some patients received more than one therapy, accounting for the difference in total numbers).
The median follow-up time was 6.5 years, with some patients on study for as long as 11.5 years.
The probability of 10-year survival was 84%, and of 10-year progression-free survival was 81%.
An analysis of survival by molecular response rates showed an overall survival rate of 89% for those who achieved a major molecular response (MR, defined as a BCR-ABL RNA level of 0.1% or less), and 74% for those who achieved MR 4.5 (a 4.5 log10reduction or greater in BCR-ABL transcripts).
The 8-year probabilities for all grades of adverse events among the patients who received imatinib monotherapy were 41% for edema or fluid overload, 38% for gastrointestinal toxicities, 25% for myalgia/arthralgia, 20% for rash, 17% for musculoskeletal events, 17% for fatigue, 11% for neurological toxicities, and 10% for flulike symptoms.
Five patients had grade 2 or 3 peripheral arterial occlusive disease, but it was not clear whether these events were associated with imatinib.
For most patients the first adverse drug reaction occurred within 3 years of starting on imatinib, with the frequency of reactions decreasing thereafter.
Dr. Hehlmann disclosed receiving research support from Novartis, marketer of imatinib.
AT THE ASCO ANNUAL MEETING 2014
Key clinical finding: Imatinib is safe and effective for treating patients with chronic myeloid leukemia over the course of a decade.
Major finding: Of 1,375 patients with CML who received imatinib (Gleevec) monotherapy, 74% had nonhematologic toxicities sometime during therapy, but only 199 (14%) had grade 3 or 4 toxicities.
Data source: Review of prospectively collected 10-year follow-up data from a phase II trial of imatinib in 1,501 patients with CML.
Disclosures: Dr. Hehlmann disclosed receiving research support from Novartis, marketer of imatinib.
Ibrutinib holds CLL at bay in majority of patients at 30 months
CHICAGO – Ibrutinib continues showing strength in a large majority of patients with chronic lymphocytic leukemia, including those with poor-prognosis chromosomal deletions, a study showed.
Three-year follow-up data of patients treated with ibrutinib (Imbruvica) monotherapy in a phase II trial and extension study showed 30-month overall survival (OS) rates of 96.6% for patients who received ibrutinib after an initial diagnosis, and 79.9% for patients with relapsed or refractory disease. Median overall survival has not been reached for either group, reported Dr. Susan M. O’Brien of the University of Texas M.D. Anderson Cancer Center, Houston.
Among patients with the poor-prognosis chromosome 17p deletion (del17p), 30-month OS was 65.9%, with the median OS not yet reached, Dr. O’Brien reported at the annual meeting of the American Society of Clinical Oncology.
"We achieved very rapid and quite durable responses with single-agent ibrutinib. We have not reached a median duration of response," she said.
The best investigator-assessed responses were 87% among 31 treatment-naive patients, and 90% among those with relapsed/refractory disease, some of whom had received four prior lines of therapy.
"I think one example of how this data will change clinical practice was the progression-free survival based on cytogenetics," commented invited discussant Dr. Nicole Lamanna of Columbia University Medical Center, New York.
The 30-month progression-free survival (PFS) by cytogenetics (as determined by fluorescence in situ hybridization) was 45.9% for patients with del17p, 74.2% for patients with the 11q deletion (del11q), and 89.0% for patients with neither deletion. The median PFS was 28.1 months among patients with del17p, but has not been reached in patients in the other two cytogenetic groups.
"With some of the other regimens that have been presented in patients with 17p, clearly a median PFS of this length has really not been achieved," she said.
In a separate study, also presented at ASCO 2014, investigators reported the results of the first interim analysis of a phase III randomized trial, which showed that 1-year overall survival for patients with previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) assigned to receive ibrutinib was 90%, compared with 81% for patients assigned to ofatumumab (Arzerra).
Independent Review
Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase, an enzyme essential for B-cell receptor signaling and adhesion that is present in many types of B-cell malignancies. Based on the results of phase II studies, ibrutinib received Food and Drug Administration approval for relapsed mantle cell lymphoma in November 2013, and for CLL in February 2014.
Dr. O’Brien and colleagues reviewed data on 31 patients aged 65 and over with newly diagnosed, untreated CLL/SLL, and 101 patients with relapsed/refractory CLL/SLL. The relapsed/refractory group included patients with high-risk CLL/SLL, defined as disease progression within 24 months of starting a chemoimmunotherapy regimen, or as a failure to respond.
The investigators initially tested ibrutinib at 420 and 840 mg daily doses, but soon discovered that there were no differences in efficacy or toxicity between the two doses. Dr. O’Brien therefore reported combined data on patients treated at each dose level.
For patients with relapsed/refractory disease, the median number of prior therapies was 4 (range, 1-12). All patients in this group had received chemotherapy, and more than 90% had received a nucleoside analogue, an alkylating agent, and anti–CD20-based therapy.
In all, 6% of treatment-naive patients and 34% of relapsed/refractory patients had del17p. Del11q was seen in 3% and 35% of patients, respectively.
At the most recent analysis, 25 of 31 treatment-naive patients (81%) and 42% of relapsed/refractory patients had been on ibrutinib for 2-3 years. Only one patient in the treatment-naive group and 19 in the relapsed/refractory group discontinued therapy because of disease progression.
Of the treatment-naive patients with responses, 13% had a complete response (CR), 3% had a near CR, 65% had a partial response (PR), and 6% had a PR with lymphocytosis. Of the relapsed/refractory group, 6% had a CR, 80% had a PR, and 4% had a PR with lymphocytosis.
The responses tend to improve over time, with a median time to first response of 1.9 months, and a median time to best response of 7.3 months.
Adverse events of grade 3 or greater occurred in 19 treatment-naive patients and 83 relapsed/refractory patients. Of these events, 7 (23%) in treatment-naive patients and 32 (32%) in relapsed/refractory patients were deemed to be ibrutinib related. One patient in the treatment-naive group and 11 in the relapsed/refractory group died during the study.
"If we look now at the adverse events over time, we see that in fact they tend to go down, and so – this is important – we’re not seeing a late, surprising side effect with 2 or 3 years of follow-up in terms of things that we didn’t see when we first started the patient on study," Dr. O’Brien said.
The most common side effects were hypertension and pneumonia.
The PCYC-1002 and -1003 studies were supported by Pharmacyclics. Dr. O’Brien disclosed receiving research funding from the company. Dr. Lamanna disclosed consulting/advising for Celgene, and receiving research funding from several companies, but not Pharmacyclics.
CHICAGO – Ibrutinib continues showing strength in a large majority of patients with chronic lymphocytic leukemia, including those with poor-prognosis chromosomal deletions, a study showed.
Three-year follow-up data of patients treated with ibrutinib (Imbruvica) monotherapy in a phase II trial and extension study showed 30-month overall survival (OS) rates of 96.6% for patients who received ibrutinib after an initial diagnosis, and 79.9% for patients with relapsed or refractory disease. Median overall survival has not been reached for either group, reported Dr. Susan M. O’Brien of the University of Texas M.D. Anderson Cancer Center, Houston.
Among patients with the poor-prognosis chromosome 17p deletion (del17p), 30-month OS was 65.9%, with the median OS not yet reached, Dr. O’Brien reported at the annual meeting of the American Society of Clinical Oncology.
"We achieved very rapid and quite durable responses with single-agent ibrutinib. We have not reached a median duration of response," she said.
The best investigator-assessed responses were 87% among 31 treatment-naive patients, and 90% among those with relapsed/refractory disease, some of whom had received four prior lines of therapy.
"I think one example of how this data will change clinical practice was the progression-free survival based on cytogenetics," commented invited discussant Dr. Nicole Lamanna of Columbia University Medical Center, New York.
The 30-month progression-free survival (PFS) by cytogenetics (as determined by fluorescence in situ hybridization) was 45.9% for patients with del17p, 74.2% for patients with the 11q deletion (del11q), and 89.0% for patients with neither deletion. The median PFS was 28.1 months among patients with del17p, but has not been reached in patients in the other two cytogenetic groups.
"With some of the other regimens that have been presented in patients with 17p, clearly a median PFS of this length has really not been achieved," she said.
In a separate study, also presented at ASCO 2014, investigators reported the results of the first interim analysis of a phase III randomized trial, which showed that 1-year overall survival for patients with previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) assigned to receive ibrutinib was 90%, compared with 81% for patients assigned to ofatumumab (Arzerra).
Independent Review
Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase, an enzyme essential for B-cell receptor signaling and adhesion that is present in many types of B-cell malignancies. Based on the results of phase II studies, ibrutinib received Food and Drug Administration approval for relapsed mantle cell lymphoma in November 2013, and for CLL in February 2014.
Dr. O’Brien and colleagues reviewed data on 31 patients aged 65 and over with newly diagnosed, untreated CLL/SLL, and 101 patients with relapsed/refractory CLL/SLL. The relapsed/refractory group included patients with high-risk CLL/SLL, defined as disease progression within 24 months of starting a chemoimmunotherapy regimen, or as a failure to respond.
The investigators initially tested ibrutinib at 420 and 840 mg daily doses, but soon discovered that there were no differences in efficacy or toxicity between the two doses. Dr. O’Brien therefore reported combined data on patients treated at each dose level.
For patients with relapsed/refractory disease, the median number of prior therapies was 4 (range, 1-12). All patients in this group had received chemotherapy, and more than 90% had received a nucleoside analogue, an alkylating agent, and anti–CD20-based therapy.
In all, 6% of treatment-naive patients and 34% of relapsed/refractory patients had del17p. Del11q was seen in 3% and 35% of patients, respectively.
At the most recent analysis, 25 of 31 treatment-naive patients (81%) and 42% of relapsed/refractory patients had been on ibrutinib for 2-3 years. Only one patient in the treatment-naive group and 19 in the relapsed/refractory group discontinued therapy because of disease progression.
Of the treatment-naive patients with responses, 13% had a complete response (CR), 3% had a near CR, 65% had a partial response (PR), and 6% had a PR with lymphocytosis. Of the relapsed/refractory group, 6% had a CR, 80% had a PR, and 4% had a PR with lymphocytosis.
The responses tend to improve over time, with a median time to first response of 1.9 months, and a median time to best response of 7.3 months.
Adverse events of grade 3 or greater occurred in 19 treatment-naive patients and 83 relapsed/refractory patients. Of these events, 7 (23%) in treatment-naive patients and 32 (32%) in relapsed/refractory patients were deemed to be ibrutinib related. One patient in the treatment-naive group and 11 in the relapsed/refractory group died during the study.
"If we look now at the adverse events over time, we see that in fact they tend to go down, and so – this is important – we’re not seeing a late, surprising side effect with 2 or 3 years of follow-up in terms of things that we didn’t see when we first started the patient on study," Dr. O’Brien said.
The most common side effects were hypertension and pneumonia.
The PCYC-1002 and -1003 studies were supported by Pharmacyclics. Dr. O’Brien disclosed receiving research funding from the company. Dr. Lamanna disclosed consulting/advising for Celgene, and receiving research funding from several companies, but not Pharmacyclics.
CHICAGO – Ibrutinib continues showing strength in a large majority of patients with chronic lymphocytic leukemia, including those with poor-prognosis chromosomal deletions, a study showed.
Three-year follow-up data of patients treated with ibrutinib (Imbruvica) monotherapy in a phase II trial and extension study showed 30-month overall survival (OS) rates of 96.6% for patients who received ibrutinib after an initial diagnosis, and 79.9% for patients with relapsed or refractory disease. Median overall survival has not been reached for either group, reported Dr. Susan M. O’Brien of the University of Texas M.D. Anderson Cancer Center, Houston.
Among patients with the poor-prognosis chromosome 17p deletion (del17p), 30-month OS was 65.9%, with the median OS not yet reached, Dr. O’Brien reported at the annual meeting of the American Society of Clinical Oncology.
"We achieved very rapid and quite durable responses with single-agent ibrutinib. We have not reached a median duration of response," she said.
The best investigator-assessed responses were 87% among 31 treatment-naive patients, and 90% among those with relapsed/refractory disease, some of whom had received four prior lines of therapy.
"I think one example of how this data will change clinical practice was the progression-free survival based on cytogenetics," commented invited discussant Dr. Nicole Lamanna of Columbia University Medical Center, New York.
The 30-month progression-free survival (PFS) by cytogenetics (as determined by fluorescence in situ hybridization) was 45.9% for patients with del17p, 74.2% for patients with the 11q deletion (del11q), and 89.0% for patients with neither deletion. The median PFS was 28.1 months among patients with del17p, but has not been reached in patients in the other two cytogenetic groups.
"With some of the other regimens that have been presented in patients with 17p, clearly a median PFS of this length has really not been achieved," she said.
In a separate study, also presented at ASCO 2014, investigators reported the results of the first interim analysis of a phase III randomized trial, which showed that 1-year overall survival for patients with previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) assigned to receive ibrutinib was 90%, compared with 81% for patients assigned to ofatumumab (Arzerra).
Independent Review
Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase, an enzyme essential for B-cell receptor signaling and adhesion that is present in many types of B-cell malignancies. Based on the results of phase II studies, ibrutinib received Food and Drug Administration approval for relapsed mantle cell lymphoma in November 2013, and for CLL in February 2014.
Dr. O’Brien and colleagues reviewed data on 31 patients aged 65 and over with newly diagnosed, untreated CLL/SLL, and 101 patients with relapsed/refractory CLL/SLL. The relapsed/refractory group included patients with high-risk CLL/SLL, defined as disease progression within 24 months of starting a chemoimmunotherapy regimen, or as a failure to respond.
The investigators initially tested ibrutinib at 420 and 840 mg daily doses, but soon discovered that there were no differences in efficacy or toxicity between the two doses. Dr. O’Brien therefore reported combined data on patients treated at each dose level.
For patients with relapsed/refractory disease, the median number of prior therapies was 4 (range, 1-12). All patients in this group had received chemotherapy, and more than 90% had received a nucleoside analogue, an alkylating agent, and anti–CD20-based therapy.
In all, 6% of treatment-naive patients and 34% of relapsed/refractory patients had del17p. Del11q was seen in 3% and 35% of patients, respectively.
At the most recent analysis, 25 of 31 treatment-naive patients (81%) and 42% of relapsed/refractory patients had been on ibrutinib for 2-3 years. Only one patient in the treatment-naive group and 19 in the relapsed/refractory group discontinued therapy because of disease progression.
Of the treatment-naive patients with responses, 13% had a complete response (CR), 3% had a near CR, 65% had a partial response (PR), and 6% had a PR with lymphocytosis. Of the relapsed/refractory group, 6% had a CR, 80% had a PR, and 4% had a PR with lymphocytosis.
The responses tend to improve over time, with a median time to first response of 1.9 months, and a median time to best response of 7.3 months.
Adverse events of grade 3 or greater occurred in 19 treatment-naive patients and 83 relapsed/refractory patients. Of these events, 7 (23%) in treatment-naive patients and 32 (32%) in relapsed/refractory patients were deemed to be ibrutinib related. One patient in the treatment-naive group and 11 in the relapsed/refractory group died during the study.
"If we look now at the adverse events over time, we see that in fact they tend to go down, and so – this is important – we’re not seeing a late, surprising side effect with 2 or 3 years of follow-up in terms of things that we didn’t see when we first started the patient on study," Dr. O’Brien said.
The most common side effects were hypertension and pneumonia.
The PCYC-1002 and -1003 studies were supported by Pharmacyclics. Dr. O’Brien disclosed receiving research funding from the company. Dr. Lamanna disclosed consulting/advising for Celgene, and receiving research funding from several companies, but not Pharmacyclics.
AT THE ASCO ANNUAL MEETING 2014
Major finding: At 30 months of follow-up, overall survival with ibrutinib monotherapy was 96.6% among patients with newly diagnosed chronic lymphocytic leukemia, and 79.9% for patients with relapsed/refractory CLL.
Data source: Long-term follow-up of 132 patients in a phase II safety and efficacy trial and extension study.
Disclosures: The PCYC-1002 and -1003 studies were supported by Pharmacyclics. Dr. O’Brien disclosed receiving research funding from the company. Dr. Lamanna disclosed consulting/advising for Celgene, and receiving research funding from several companies, but not Pharmacyclics.
