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European Society for Medical Oncology (ESMO) 39th Congress
CLEOPATRA sets new standard treatment paradigm for metastatic breast cancer
MADRID – First-line dual targeted therapy with pertuzumab and trastuzumab plus chemotherapy gives women with HER2-positive metastatic breast cancer an additional 15.7 months of life, according to the final overall survival analysis of the long-running CLEOPATRA trial.
After a median of 50 months follow-up, median overall survival was 40.8 months with trastuzumab (Herceptin) and docetaxel chemotherapy and 56.5 months with the addition of pertuzumab (Perjeta) (Hazard ratio, 0.68; P = .0002).
The benefit was consistent across all subgroups and did not come at the expense of added toxicities or long-term cardiac safety.
The 56.5-month survival advantage is unprecedented in this indication and sets a new standard of care, lead author Dr. Sandra Swain said during a presidential symposium at the European Society for Medical Oncology Congress.
Discussant Dr. Luca Gianni, with the San Raffaele Scientific Institute, in Milan, Italy, agreed, saying “CLEOPATRA is an unprecedented therapeutic success, with the unquestionable clinical implication that docetaxel, trastuzumab, and pertuzumab is the new standard, and not an option, for first-line treatment of HER2-positive metastatic breast cancer.”
In the first interim survival analysis from CLEOPATRA, there was a trend toward improved overall survival favoring pertuzumab, trastuzumab, and docetaxel.
The overall survival benefit reached statistical significance after a median follow-up of 30 months in the second interim analysis (Lancet Oncol. 2013;14:461-71) and was accompanied by a 6.3-month benefit in median progression-free survival (PFS) (18.7 months vs. 12.4 months).
The PFS gain was maintained with the longer follow-up (HR, 0.68; P less than .0001), indicating that PFS is a good surrogate for overall survival, noted Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center.
The phase III, double-blind trial randomized 808 women with HER2-positive metastatic, locally recurrent, or unresectable breast cancer to trastuzumab and at least six cycles of docetaxel chemotherapy with placebo or pertuzumab. The final survival analysis was planned after 385 reported deaths.
More than 70% of patients had visceral disease, roughly half were hormone receptor (HR) status positive and half HR negative, 53% had no prior neoadjuvant/adjuvant chemotherapy, and only about 10% had received prior trastuzumab. Their median age was 54 years.
During a press briefing on CLEOPATRA, Dr. Swain said the median survival with trastuzumab is already quite good at 40.8 months, but that the 15.6-month gain in overall survival with the addition of pertuzumab has not been seen before in this setting and is the kind of improvement oncologists hope for throughout their careers.
Cardiac safety was a concern with the two monoclonal antibodies, but there was only one new symptomatic heart failure in the pertuzumab group after 40 months and it resolved after treatment was stopped, she said. Rates of left ventricular ejection fraction (LVEF) decline to less than 50% and by at least 10% from baseline were also lower in the pertuzumab group than in the trastuzumab/docetaxel group (6.1% vs. 7.4%). LVEF declines were reversed in 88% of pertuzumab patients.
When asked whether both monoclonal antibodies are needed in the regimen, Dr. Swain said she would give her patients both.
Dr. Gianni observed that pertuzumab acts synergistically with trastuzumab and that neoadjuvant pertuzumab and trastuzumab plus chemotherapy improved complete responses in early breast cancer in the phase II NeoSphere trial he led (Lancet Oncol. 2012;13:25-32).
The phase III APHINITYtrial is also well underway in the adjuvant setting of HER2-positive disease, comparing pertuzumab, trastuzumab, and chemotherapy against trastuzumab and chemotherapy alone. If the results from CLEOPATRA in the metastatic setting are confirmed in APHINITY, it could provide a new standard of care in the adjuvant setting, he said.
Dr. Gianni said the CLEOPATRA results can be improved only by addressing key features of HER2-positive breast cancer linked to different sensitivity such as hormone receptor status, P1K3CA status, and the immune environment. NeoSphere and other studies have shown, for example, that estrogen- and progesterone-receptor positive, HER2-positive disease is less responsive to the treatment used in CLEOPATRA. The CLEOPATRA protocol, however, did not allow for endocrine therapy of patients with estrogen-receptor positive tumors, though dual blockade of HER2 with pertuzumab, trastuzumab, and concomitant endocrine therapy has been shown to be feasible and is actually being done in the adjuvant setting in APHINITY.
Thus, “The question is whether the addition of endocrine therapy after the end of chemotherapy in CLEOPATRA could have increased the already large benefit observed in women with HER2-positive, estrogen receptor-positive metastatic breast cancer,” he said.
MADRID – First-line dual targeted therapy with pertuzumab and trastuzumab plus chemotherapy gives women with HER2-positive metastatic breast cancer an additional 15.7 months of life, according to the final overall survival analysis of the long-running CLEOPATRA trial.
After a median of 50 months follow-up, median overall survival was 40.8 months with trastuzumab (Herceptin) and docetaxel chemotherapy and 56.5 months with the addition of pertuzumab (Perjeta) (Hazard ratio, 0.68; P = .0002).
The benefit was consistent across all subgroups and did not come at the expense of added toxicities or long-term cardiac safety.
The 56.5-month survival advantage is unprecedented in this indication and sets a new standard of care, lead author Dr. Sandra Swain said during a presidential symposium at the European Society for Medical Oncology Congress.
Discussant Dr. Luca Gianni, with the San Raffaele Scientific Institute, in Milan, Italy, agreed, saying “CLEOPATRA is an unprecedented therapeutic success, with the unquestionable clinical implication that docetaxel, trastuzumab, and pertuzumab is the new standard, and not an option, for first-line treatment of HER2-positive metastatic breast cancer.”
In the first interim survival analysis from CLEOPATRA, there was a trend toward improved overall survival favoring pertuzumab, trastuzumab, and docetaxel.
The overall survival benefit reached statistical significance after a median follow-up of 30 months in the second interim analysis (Lancet Oncol. 2013;14:461-71) and was accompanied by a 6.3-month benefit in median progression-free survival (PFS) (18.7 months vs. 12.4 months).
The PFS gain was maintained with the longer follow-up (HR, 0.68; P less than .0001), indicating that PFS is a good surrogate for overall survival, noted Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center.
The phase III, double-blind trial randomized 808 women with HER2-positive metastatic, locally recurrent, or unresectable breast cancer to trastuzumab and at least six cycles of docetaxel chemotherapy with placebo or pertuzumab. The final survival analysis was planned after 385 reported deaths.
More than 70% of patients had visceral disease, roughly half were hormone receptor (HR) status positive and half HR negative, 53% had no prior neoadjuvant/adjuvant chemotherapy, and only about 10% had received prior trastuzumab. Their median age was 54 years.
During a press briefing on CLEOPATRA, Dr. Swain said the median survival with trastuzumab is already quite good at 40.8 months, but that the 15.6-month gain in overall survival with the addition of pertuzumab has not been seen before in this setting and is the kind of improvement oncologists hope for throughout their careers.
Cardiac safety was a concern with the two monoclonal antibodies, but there was only one new symptomatic heart failure in the pertuzumab group after 40 months and it resolved after treatment was stopped, she said. Rates of left ventricular ejection fraction (LVEF) decline to less than 50% and by at least 10% from baseline were also lower in the pertuzumab group than in the trastuzumab/docetaxel group (6.1% vs. 7.4%). LVEF declines were reversed in 88% of pertuzumab patients.
When asked whether both monoclonal antibodies are needed in the regimen, Dr. Swain said she would give her patients both.
Dr. Gianni observed that pertuzumab acts synergistically with trastuzumab and that neoadjuvant pertuzumab and trastuzumab plus chemotherapy improved complete responses in early breast cancer in the phase II NeoSphere trial he led (Lancet Oncol. 2012;13:25-32).
The phase III APHINITYtrial is also well underway in the adjuvant setting of HER2-positive disease, comparing pertuzumab, trastuzumab, and chemotherapy against trastuzumab and chemotherapy alone. If the results from CLEOPATRA in the metastatic setting are confirmed in APHINITY, it could provide a new standard of care in the adjuvant setting, he said.
Dr. Gianni said the CLEOPATRA results can be improved only by addressing key features of HER2-positive breast cancer linked to different sensitivity such as hormone receptor status, P1K3CA status, and the immune environment. NeoSphere and other studies have shown, for example, that estrogen- and progesterone-receptor positive, HER2-positive disease is less responsive to the treatment used in CLEOPATRA. The CLEOPATRA protocol, however, did not allow for endocrine therapy of patients with estrogen-receptor positive tumors, though dual blockade of HER2 with pertuzumab, trastuzumab, and concomitant endocrine therapy has been shown to be feasible and is actually being done in the adjuvant setting in APHINITY.
Thus, “The question is whether the addition of endocrine therapy after the end of chemotherapy in CLEOPATRA could have increased the already large benefit observed in women with HER2-positive, estrogen receptor-positive metastatic breast cancer,” he said.
MADRID – First-line dual targeted therapy with pertuzumab and trastuzumab plus chemotherapy gives women with HER2-positive metastatic breast cancer an additional 15.7 months of life, according to the final overall survival analysis of the long-running CLEOPATRA trial.
After a median of 50 months follow-up, median overall survival was 40.8 months with trastuzumab (Herceptin) and docetaxel chemotherapy and 56.5 months with the addition of pertuzumab (Perjeta) (Hazard ratio, 0.68; P = .0002).
The benefit was consistent across all subgroups and did not come at the expense of added toxicities or long-term cardiac safety.
The 56.5-month survival advantage is unprecedented in this indication and sets a new standard of care, lead author Dr. Sandra Swain said during a presidential symposium at the European Society for Medical Oncology Congress.
Discussant Dr. Luca Gianni, with the San Raffaele Scientific Institute, in Milan, Italy, agreed, saying “CLEOPATRA is an unprecedented therapeutic success, with the unquestionable clinical implication that docetaxel, trastuzumab, and pertuzumab is the new standard, and not an option, for first-line treatment of HER2-positive metastatic breast cancer.”
In the first interim survival analysis from CLEOPATRA, there was a trend toward improved overall survival favoring pertuzumab, trastuzumab, and docetaxel.
The overall survival benefit reached statistical significance after a median follow-up of 30 months in the second interim analysis (Lancet Oncol. 2013;14:461-71) and was accompanied by a 6.3-month benefit in median progression-free survival (PFS) (18.7 months vs. 12.4 months).
The PFS gain was maintained with the longer follow-up (HR, 0.68; P less than .0001), indicating that PFS is a good surrogate for overall survival, noted Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center.
The phase III, double-blind trial randomized 808 women with HER2-positive metastatic, locally recurrent, or unresectable breast cancer to trastuzumab and at least six cycles of docetaxel chemotherapy with placebo or pertuzumab. The final survival analysis was planned after 385 reported deaths.
More than 70% of patients had visceral disease, roughly half were hormone receptor (HR) status positive and half HR negative, 53% had no prior neoadjuvant/adjuvant chemotherapy, and only about 10% had received prior trastuzumab. Their median age was 54 years.
During a press briefing on CLEOPATRA, Dr. Swain said the median survival with trastuzumab is already quite good at 40.8 months, but that the 15.6-month gain in overall survival with the addition of pertuzumab has not been seen before in this setting and is the kind of improvement oncologists hope for throughout their careers.
Cardiac safety was a concern with the two monoclonal antibodies, but there was only one new symptomatic heart failure in the pertuzumab group after 40 months and it resolved after treatment was stopped, she said. Rates of left ventricular ejection fraction (LVEF) decline to less than 50% and by at least 10% from baseline were also lower in the pertuzumab group than in the trastuzumab/docetaxel group (6.1% vs. 7.4%). LVEF declines were reversed in 88% of pertuzumab patients.
When asked whether both monoclonal antibodies are needed in the regimen, Dr. Swain said she would give her patients both.
Dr. Gianni observed that pertuzumab acts synergistically with trastuzumab and that neoadjuvant pertuzumab and trastuzumab plus chemotherapy improved complete responses in early breast cancer in the phase II NeoSphere trial he led (Lancet Oncol. 2012;13:25-32).
The phase III APHINITYtrial is also well underway in the adjuvant setting of HER2-positive disease, comparing pertuzumab, trastuzumab, and chemotherapy against trastuzumab and chemotherapy alone. If the results from CLEOPATRA in the metastatic setting are confirmed in APHINITY, it could provide a new standard of care in the adjuvant setting, he said.
Dr. Gianni said the CLEOPATRA results can be improved only by addressing key features of HER2-positive breast cancer linked to different sensitivity such as hormone receptor status, P1K3CA status, and the immune environment. NeoSphere and other studies have shown, for example, that estrogen- and progesterone-receptor positive, HER2-positive disease is less responsive to the treatment used in CLEOPATRA. The CLEOPATRA protocol, however, did not allow for endocrine therapy of patients with estrogen-receptor positive tumors, though dual blockade of HER2 with pertuzumab, trastuzumab, and concomitant endocrine therapy has been shown to be feasible and is actually being done in the adjuvant setting in APHINITY.
Thus, “The question is whether the addition of endocrine therapy after the end of chemotherapy in CLEOPATRA could have increased the already large benefit observed in women with HER2-positive, estrogen receptor-positive metastatic breast cancer,” he said.
AT ESMO 2014
Key clinical point: Pertuzumab, trastuzumab, and docetaxel chemotherapy is the new standard for first-line metastatic HER2-positive breast cancer.
Major finding: Median overall survival was 40.8 months with trastuzumab and chemotherapy and 56.5 months with the addition of pertuzumab.
Data source: Phase III trial in 808 women with metastatic HER2-positive breast cancer.
Disclosures: The study was funded by Hoffman-LaRoche and Genentech. Dr. Swain reported serving as an uncompensated consultant for Genentech/Roche.
Rolapitant curbs chemo-induced nausea and vomiting
MADRID – The investigational neurokinin-1 receptor antagonist rolapitant met all of its endpoints in the prevention of chemotherapy-induced nausea and vomiting in a phase III trial.
Among 532 patients receiving cisplatin chemotherapy, 72.7% randomized to oral rolapitant versus 58.4% on placebo achieved the primary endpoint of complete response, defined as no emesis or use of rescue medication, in the delayed phase of more than 24 hours to 120 hours following chemotherapy (P less than .001).
Complete responses also were higher with rolapitant in the acute phase (0-24 hours) post chemotherapy (83.7% vs. 73.7%; P = .005) and the overall phase (0-120 hours) post chemotherapy (70.1% vs. 56.5%; P = .001), according to a late-breaking abstract reported at the European Society for Medical Oncology Congress.
Rolapitant works by blocking activation of neurokinin (NK)-1 receptors concentrated in the brain, which play a central role in nausea and vomiting.
Rolapitant is unique in that it has an extremely long half-life of 180 hours and NK-1 receptor occupancy of more than 90% for up to 5 days, study coauthor Dr. Bernardo Rapoport of the Medical Oncology Centre of Rosebank, Johannesburg, South Africa, explained during a press briefing on the study.
Kaplan-Meier analysis suggests that the effect of rolapitant begins in the acute phase, with separation of the curves beginning at about 12 hours.
More than 85% of cancer patients not treated appropriately can be affected by chemotherapy-induced nausea and vomiting, Dr. Rapoport said, adding that active management of this “most feared” side effect can improve quality of life and compliance with cancer treatment.
There was a slight improvement in quality of life in the rolapitant arm versus controls, as measured by the Functional Living Index-Emesis questionnaire (mean total score 112.5 vs. 108.4; P = .032).
Patients in the study were evenly randomized on the day of chemotherapy to oral rolapitant 200 mg or placebo, plus intravenous granisetron and oral dexamethasone.
Treatment-related adverse events were consistent across both arms, with most considered related to chemotherapy or the underlying cancer, Dr. Rapoport said.
Rolapitant is being developed by Tesaro in oral and intravenous formulations. A new drug application was filed in September 2014 with the U.S. Food and Drug Administration for oral rolapitant based on results from four controlled trials.
Rolapitant will face stiff competition in the market from Merck’s long-standing NK1 receptor antagonist, aprepitant (Emend), which is approved for prevention of chemotherapy-induced nausea and vomiting in combination with a corticosteroid and a 5-HT₃ antagonist. Rolapitant failed to meet a key secondary endpoint in a phase III trial last year, sending Tesaro stocks tumbling.
MADRID – The investigational neurokinin-1 receptor antagonist rolapitant met all of its endpoints in the prevention of chemotherapy-induced nausea and vomiting in a phase III trial.
Among 532 patients receiving cisplatin chemotherapy, 72.7% randomized to oral rolapitant versus 58.4% on placebo achieved the primary endpoint of complete response, defined as no emesis or use of rescue medication, in the delayed phase of more than 24 hours to 120 hours following chemotherapy (P less than .001).
Complete responses also were higher with rolapitant in the acute phase (0-24 hours) post chemotherapy (83.7% vs. 73.7%; P = .005) and the overall phase (0-120 hours) post chemotherapy (70.1% vs. 56.5%; P = .001), according to a late-breaking abstract reported at the European Society for Medical Oncology Congress.
Rolapitant works by blocking activation of neurokinin (NK)-1 receptors concentrated in the brain, which play a central role in nausea and vomiting.
Rolapitant is unique in that it has an extremely long half-life of 180 hours and NK-1 receptor occupancy of more than 90% for up to 5 days, study coauthor Dr. Bernardo Rapoport of the Medical Oncology Centre of Rosebank, Johannesburg, South Africa, explained during a press briefing on the study.
Kaplan-Meier analysis suggests that the effect of rolapitant begins in the acute phase, with separation of the curves beginning at about 12 hours.
More than 85% of cancer patients not treated appropriately can be affected by chemotherapy-induced nausea and vomiting, Dr. Rapoport said, adding that active management of this “most feared” side effect can improve quality of life and compliance with cancer treatment.
There was a slight improvement in quality of life in the rolapitant arm versus controls, as measured by the Functional Living Index-Emesis questionnaire (mean total score 112.5 vs. 108.4; P = .032).
Patients in the study were evenly randomized on the day of chemotherapy to oral rolapitant 200 mg or placebo, plus intravenous granisetron and oral dexamethasone.
Treatment-related adverse events were consistent across both arms, with most considered related to chemotherapy or the underlying cancer, Dr. Rapoport said.
Rolapitant is being developed by Tesaro in oral and intravenous formulations. A new drug application was filed in September 2014 with the U.S. Food and Drug Administration for oral rolapitant based on results from four controlled trials.
Rolapitant will face stiff competition in the market from Merck’s long-standing NK1 receptor antagonist, aprepitant (Emend), which is approved for prevention of chemotherapy-induced nausea and vomiting in combination with a corticosteroid and a 5-HT₃ antagonist. Rolapitant failed to meet a key secondary endpoint in a phase III trial last year, sending Tesaro stocks tumbling.
MADRID – The investigational neurokinin-1 receptor antagonist rolapitant met all of its endpoints in the prevention of chemotherapy-induced nausea and vomiting in a phase III trial.
Among 532 patients receiving cisplatin chemotherapy, 72.7% randomized to oral rolapitant versus 58.4% on placebo achieved the primary endpoint of complete response, defined as no emesis or use of rescue medication, in the delayed phase of more than 24 hours to 120 hours following chemotherapy (P less than .001).
Complete responses also were higher with rolapitant in the acute phase (0-24 hours) post chemotherapy (83.7% vs. 73.7%; P = .005) and the overall phase (0-120 hours) post chemotherapy (70.1% vs. 56.5%; P = .001), according to a late-breaking abstract reported at the European Society for Medical Oncology Congress.
Rolapitant works by blocking activation of neurokinin (NK)-1 receptors concentrated in the brain, which play a central role in nausea and vomiting.
Rolapitant is unique in that it has an extremely long half-life of 180 hours and NK-1 receptor occupancy of more than 90% for up to 5 days, study coauthor Dr. Bernardo Rapoport of the Medical Oncology Centre of Rosebank, Johannesburg, South Africa, explained during a press briefing on the study.
Kaplan-Meier analysis suggests that the effect of rolapitant begins in the acute phase, with separation of the curves beginning at about 12 hours.
More than 85% of cancer patients not treated appropriately can be affected by chemotherapy-induced nausea and vomiting, Dr. Rapoport said, adding that active management of this “most feared” side effect can improve quality of life and compliance with cancer treatment.
There was a slight improvement in quality of life in the rolapitant arm versus controls, as measured by the Functional Living Index-Emesis questionnaire (mean total score 112.5 vs. 108.4; P = .032).
Patients in the study were evenly randomized on the day of chemotherapy to oral rolapitant 200 mg or placebo, plus intravenous granisetron and oral dexamethasone.
Treatment-related adverse events were consistent across both arms, with most considered related to chemotherapy or the underlying cancer, Dr. Rapoport said.
Rolapitant is being developed by Tesaro in oral and intravenous formulations. A new drug application was filed in September 2014 with the U.S. Food and Drug Administration for oral rolapitant based on results from four controlled trials.
Rolapitant will face stiff competition in the market from Merck’s long-standing NK1 receptor antagonist, aprepitant (Emend), which is approved for prevention of chemotherapy-induced nausea and vomiting in combination with a corticosteroid and a 5-HT₃ antagonist. Rolapitant failed to meet a key secondary endpoint in a phase III trial last year, sending Tesaro stocks tumbling.
AT ESMO 2014
Key clinical point: Rolapitant was significantly better than placebo in reducing chemotherapy-induced nausea and vomiting.
Major finding: Complete responses were significantly higher with rolapitant than placebo in the delayed phase post chemotherapy (72.7% vs. 58.4%; P < .001).
Data source: Phase III trial in 532 patients receiving cisplatin chemotherapy.
Disclosures: Dr. Rapoport and lead author Dr. Martin Chasen reported no financial disclosures; several coauthors are employees of the study sponsor, Tesaro.
New drug boosts survival in metastatic CRC
MADRID – Treatment with a new nucleoside-analogue drug produced clinically meaningful improvements in survival and performance status in a phase III trial that enrolled 800 patients with metastatic colorectal cancer who had failed at least two prior chemotherapy regimens.
In addition to a statistically significant, 32% cut in mortality during a median follow-up of 8 months, treatment with TAS-102 was “well tolerated,” and extended the time to deterioration of performance status by more than 40% compared with patients randomized to placebo, Dr. Erik Van Cutsem said at the European Society for Medical Oncology Congress.
S-102’s ability to stabilize patient performance status, along with its benefit for the study’s primary endpoint of overall survival, is “an important clinical parameter, a real benefit” that shows the drug’s positive effect on quality of life, said Dr. Cutsem, professor and head of clinical digestive oncology at the University Hospital, Leuven, Belgium.
TAS-102 contains trifluridine, a nucleoside analogue that gets incorporated into tumor cell DNA, causing dysfunction and inhibited tumor growth. A second agent in the TAS-120 formulation, tipiracil hydrochloride, inhibits trifluridine breakdown.
The RECOURSE (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) trial randomized 800 patients with metastatic colorectal cancer who had failed at least two prior regimens at 114 sites in 13 countries from June 2012 to October 2013. More than half the patients had failed or were intolerant of at least four prior regimens, and more than three-quarters of enrolled patients had been diagnosed with metastatic disease 18 months prior to study entry. Patients’ median age was 63 years, and at entry they all had an Eastern Cooperative Oncology Group performance status rating of 0 or 1.
Patients received 35 mg/m2 oral TAS-102 b.i.d. on days 1-5 and 8-12 for one cycle, repeated every 4 weeks, or placebo in addition to best supportive care. Treatment with the active agent produced a hazard ratio of 0.68 (confidence interval, 0.58-0.81; P < .0001), Dr. Van Cutsem reported. After 1 year, 27% of the 534 patients on TAS-102 treatment remained alive, compared with 18% of the 266 patients randomized to placebo. Prespecified subgroup analyses showed a consistent benefit across all subgroups.
A multivariate analysis showed a similar impact of treatment on overall survival. Secondary analysis showed that TAS-102 treatment was linked to a significant improvement in progression-free survival (HR, 0.48; CI, 0.41-0.57; P < .0001). The median time to deterioration to a performance status rating of 2 was 5.7 months among patients who received TAS-102 and 4.0 months among placebo patients.
TAS-102 produced a low level of nonhematologic grade 3 or 4 adverse events. The most common, usually grade 1 or 2, were nausea, fatigue, diarrhea, and vomiting. It did not produce any excess cardiac or thromboembolic events, and had no effect on liver function or creatinine levels. The novel agent produced a 38% incidence of grade 3 or 4 neutropenia, but grade 3 or 4 febrile neutropenia was limited to 4% of patients, Dr. Van Cutsem noted. Grade 3 anemia occurred in 18% of patients on the combination agent, and 5% had grade 3 or 4 thrombocytopenia.
RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi.
On Twitter @mitchelzoler
The results of RECOURSE were robust and convincing and clearly in favor of TAS-102. This will be a very important drug in the future.
The efficacy of TAS-102 looks similar to what was recently reported for regorafenib in similar patients with refractory, metastatic colorectal cancer (Lancet 2013;381:303-12), which now makes these two agents competitors in the same situation. But TAS-102 and regorafenib have substantially different safety profiles. TAS-102 treatment produced many episodes of grade 3 or 4 neutropenia, but a much smaller number of patients developed febrile neutropenia. This toxicity is manageable. TAS-102 does not cause the hand-foot syndrome that regorafenib often triggers.
 |
| Mitchel L. Zoler/Frontline Medical News Dr. Christophe Tournigand |
The efficacy of TAS-102 in the very advanced cases enrolled in the trial raises questions about how it will perform when used on less advanced patients, and whether it has a role as first- or second-line treatment. It will also be important to determine how well TAS-102 can be used in combination with other drugs; I suspect it may be easier to combine with other agents than regorafenib. TAS-102 has a mechanism of action very similar to that of fluorouracil, and it is intriguing to imagine that perhaps someday TAS-102 will replace fluorouracil as a mainstay of colorectal cancer treatment.
Dr. Christophe Tournigand is professor and head of medical oncology at Henri Mondor University Hospital in Créteil, France. He has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer. He made these comments as designated discussant for the RECOURSE trial and in an interview.
The results of RECOURSE were robust and convincing and clearly in favor of TAS-102. This will be a very important drug in the future.
The efficacy of TAS-102 looks similar to what was recently reported for regorafenib in similar patients with refractory, metastatic colorectal cancer (Lancet 2013;381:303-12), which now makes these two agents competitors in the same situation. But TAS-102 and regorafenib have substantially different safety profiles. TAS-102 treatment produced many episodes of grade 3 or 4 neutropenia, but a much smaller number of patients developed febrile neutropenia. This toxicity is manageable. TAS-102 does not cause the hand-foot syndrome that regorafenib often triggers.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Christophe Tournigand |
The efficacy of TAS-102 in the very advanced cases enrolled in the trial raises questions about how it will perform when used on less advanced patients, and whether it has a role as first- or second-line treatment. It will also be important to determine how well TAS-102 can be used in combination with other drugs; I suspect it may be easier to combine with other agents than regorafenib. TAS-102 has a mechanism of action very similar to that of fluorouracil, and it is intriguing to imagine that perhaps someday TAS-102 will replace fluorouracil as a mainstay of colorectal cancer treatment.
Dr. Christophe Tournigand is professor and head of medical oncology at Henri Mondor University Hospital in Créteil, France. He has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer. He made these comments as designated discussant for the RECOURSE trial and in an interview.
The results of RECOURSE were robust and convincing and clearly in favor of TAS-102. This will be a very important drug in the future.
The efficacy of TAS-102 looks similar to what was recently reported for regorafenib in similar patients with refractory, metastatic colorectal cancer (Lancet 2013;381:303-12), which now makes these two agents competitors in the same situation. But TAS-102 and regorafenib have substantially different safety profiles. TAS-102 treatment produced many episodes of grade 3 or 4 neutropenia, but a much smaller number of patients developed febrile neutropenia. This toxicity is manageable. TAS-102 does not cause the hand-foot syndrome that regorafenib often triggers.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Christophe Tournigand |
The efficacy of TAS-102 in the very advanced cases enrolled in the trial raises questions about how it will perform when used on less advanced patients, and whether it has a role as first- or second-line treatment. It will also be important to determine how well TAS-102 can be used in combination with other drugs; I suspect it may be easier to combine with other agents than regorafenib. TAS-102 has a mechanism of action very similar to that of fluorouracil, and it is intriguing to imagine that perhaps someday TAS-102 will replace fluorouracil as a mainstay of colorectal cancer treatment.
Dr. Christophe Tournigand is professor and head of medical oncology at Henri Mondor University Hospital in Créteil, France. He has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer. He made these comments as designated discussant for the RECOURSE trial and in an interview.
MADRID – Treatment with a new nucleoside-analogue drug produced clinically meaningful improvements in survival and performance status in a phase III trial that enrolled 800 patients with metastatic colorectal cancer who had failed at least two prior chemotherapy regimens.
In addition to a statistically significant, 32% cut in mortality during a median follow-up of 8 months, treatment with TAS-102 was “well tolerated,” and extended the time to deterioration of performance status by more than 40% compared with patients randomized to placebo, Dr. Erik Van Cutsem said at the European Society for Medical Oncology Congress.
S-102’s ability to stabilize patient performance status, along with its benefit for the study’s primary endpoint of overall survival, is “an important clinical parameter, a real benefit” that shows the drug’s positive effect on quality of life, said Dr. Cutsem, professor and head of clinical digestive oncology at the University Hospital, Leuven, Belgium.
TAS-102 contains trifluridine, a nucleoside analogue that gets incorporated into tumor cell DNA, causing dysfunction and inhibited tumor growth. A second agent in the TAS-120 formulation, tipiracil hydrochloride, inhibits trifluridine breakdown.
The RECOURSE (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) trial randomized 800 patients with metastatic colorectal cancer who had failed at least two prior regimens at 114 sites in 13 countries from June 2012 to October 2013. More than half the patients had failed or were intolerant of at least four prior regimens, and more than three-quarters of enrolled patients had been diagnosed with metastatic disease 18 months prior to study entry. Patients’ median age was 63 years, and at entry they all had an Eastern Cooperative Oncology Group performance status rating of 0 or 1.
Patients received 35 mg/m2 oral TAS-102 b.i.d. on days 1-5 and 8-12 for one cycle, repeated every 4 weeks, or placebo in addition to best supportive care. Treatment with the active agent produced a hazard ratio of 0.68 (confidence interval, 0.58-0.81; P < .0001), Dr. Van Cutsem reported. After 1 year, 27% of the 534 patients on TAS-102 treatment remained alive, compared with 18% of the 266 patients randomized to placebo. Prespecified subgroup analyses showed a consistent benefit across all subgroups.
A multivariate analysis showed a similar impact of treatment on overall survival. Secondary analysis showed that TAS-102 treatment was linked to a significant improvement in progression-free survival (HR, 0.48; CI, 0.41-0.57; P < .0001). The median time to deterioration to a performance status rating of 2 was 5.7 months among patients who received TAS-102 and 4.0 months among placebo patients.
TAS-102 produced a low level of nonhematologic grade 3 or 4 adverse events. The most common, usually grade 1 or 2, were nausea, fatigue, diarrhea, and vomiting. It did not produce any excess cardiac or thromboembolic events, and had no effect on liver function or creatinine levels. The novel agent produced a 38% incidence of grade 3 or 4 neutropenia, but grade 3 or 4 febrile neutropenia was limited to 4% of patients, Dr. Van Cutsem noted. Grade 3 anemia occurred in 18% of patients on the combination agent, and 5% had grade 3 or 4 thrombocytopenia.
RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi.
On Twitter @mitchelzoler
MADRID – Treatment with a new nucleoside-analogue drug produced clinically meaningful improvements in survival and performance status in a phase III trial that enrolled 800 patients with metastatic colorectal cancer who had failed at least two prior chemotherapy regimens.
In addition to a statistically significant, 32% cut in mortality during a median follow-up of 8 months, treatment with TAS-102 was “well tolerated,” and extended the time to deterioration of performance status by more than 40% compared with patients randomized to placebo, Dr. Erik Van Cutsem said at the European Society for Medical Oncology Congress.
S-102’s ability to stabilize patient performance status, along with its benefit for the study’s primary endpoint of overall survival, is “an important clinical parameter, a real benefit” that shows the drug’s positive effect on quality of life, said Dr. Cutsem, professor and head of clinical digestive oncology at the University Hospital, Leuven, Belgium.
TAS-102 contains trifluridine, a nucleoside analogue that gets incorporated into tumor cell DNA, causing dysfunction and inhibited tumor growth. A second agent in the TAS-120 formulation, tipiracil hydrochloride, inhibits trifluridine breakdown.
The RECOURSE (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) trial randomized 800 patients with metastatic colorectal cancer who had failed at least two prior regimens at 114 sites in 13 countries from June 2012 to October 2013. More than half the patients had failed or were intolerant of at least four prior regimens, and more than three-quarters of enrolled patients had been diagnosed with metastatic disease 18 months prior to study entry. Patients’ median age was 63 years, and at entry they all had an Eastern Cooperative Oncology Group performance status rating of 0 or 1.
Patients received 35 mg/m2 oral TAS-102 b.i.d. on days 1-5 and 8-12 for one cycle, repeated every 4 weeks, or placebo in addition to best supportive care. Treatment with the active agent produced a hazard ratio of 0.68 (confidence interval, 0.58-0.81; P < .0001), Dr. Van Cutsem reported. After 1 year, 27% of the 534 patients on TAS-102 treatment remained alive, compared with 18% of the 266 patients randomized to placebo. Prespecified subgroup analyses showed a consistent benefit across all subgroups.
A multivariate analysis showed a similar impact of treatment on overall survival. Secondary analysis showed that TAS-102 treatment was linked to a significant improvement in progression-free survival (HR, 0.48; CI, 0.41-0.57; P < .0001). The median time to deterioration to a performance status rating of 2 was 5.7 months among patients who received TAS-102 and 4.0 months among placebo patients.
TAS-102 produced a low level of nonhematologic grade 3 or 4 adverse events. The most common, usually grade 1 or 2, were nausea, fatigue, diarrhea, and vomiting. It did not produce any excess cardiac or thromboembolic events, and had no effect on liver function or creatinine levels. The novel agent produced a 38% incidence of grade 3 or 4 neutropenia, but grade 3 or 4 febrile neutropenia was limited to 4% of patients, Dr. Van Cutsem noted. Grade 3 anemia occurred in 18% of patients on the combination agent, and 5% had grade 3 or 4 thrombocytopenia.
RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi.
On Twitter @mitchelzoler
AT ESMO 2014
Key clinical point: TAS-102 treatment significantly boosted overall survival with good tolerability in patients with metastatic colorectal cancer refractory to at least two prior treatments in a phase III study.
Major finding: TAS-102 treatment improved overall survival by a hazard ratio of 0.68 compared with placebo.
Data source: RECOURSE, a randomized study with 800 patients at 114 centers in 13 countries.
Disclosures: RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi. Dr. Tournigand has been an adviser to Roche, Sanofi, Merck, Amgen, and Bayer.
VIDEO: MEK/BRAF combo puts brakes on BRAF-mutated advanced melanoma progression
MADRID – Combining the investigational MEK inhibitor cobimetinib with the BRAF inhibitor vemurafenib nearly halved the risk of progression in previously untreated patients with BRAF-mutated advanced melanoma in the ongoing, phase III coBRIM study.
Median progression-free survival by investigator was 6.2 months with vemurafenib (Zelboraf) and 9.9 months with the combination (Hazard ratio 0.51; P less than .0001); by independent review, median progression-free survival was 6.0 months versus 11.3 months, respectively (HR, 0.60; P = .0003), study author Dr. Grant McArthur reported in a late-breaking abstract at the European Society for Medical Oncology Congress.
Combination therapy also resulted in a significantly higher objective response rate (68% vs. 45%; P less than .0001) and more complete responses (10% vs. 4%) among the 495 patients with unresectable, locally advanced or metastatic BRAF V600 mutation–positive disease.
Overall survival data are not yet mature, but the interim analysis showed a promising 35% reduction in the risk of death at 9 months (HR, 0.65), said Dr. McArthur of the Peter MacCallum Cancer Centre, Melbourne, Australia. The corresponding P value of .046 is descriptive, as it did not cross the prespecified stopping boundary for the interim analysis.
Grade 3 toxicity, albeit fairly common, was slightly higher with combination therapy vs. vemurafenib alone (65% vs. 59%). Adverse event–related treatment discontinuations were similar between arms (13% vs. 12%), he said.
The data, which were simultaneously published in the New England Journal of Medicine (2014 Sept. 29 [doi:10.1056/NEJMoa1408868]) are expected to be submitted to the U.S. Food and Drug Administration later this year for potential approval of cobimetinib. Vemurafenib was approved in the United States for late-stage or unresectable melanoma in August 2011.
In our video interview, Dr. McArthur discusses coBRIM and his suggestions for how clinicians may incorporate this novel strategy into practice.
coBRIM was funded by F. Hoffmann-LaRoche/Genentech. Dr. McArthur reported grants from Roche, Novartis, Pfizer, Millennium, and Celegene, and consulting for Provectus.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Combining the investigational MEK inhibitor cobimetinib with the BRAF inhibitor vemurafenib nearly halved the risk of progression in previously untreated patients with BRAF-mutated advanced melanoma in the ongoing, phase III coBRIM study.
Median progression-free survival by investigator was 6.2 months with vemurafenib (Zelboraf) and 9.9 months with the combination (Hazard ratio 0.51; P less than .0001); by independent review, median progression-free survival was 6.0 months versus 11.3 months, respectively (HR, 0.60; P = .0003), study author Dr. Grant McArthur reported in a late-breaking abstract at the European Society for Medical Oncology Congress.
Combination therapy also resulted in a significantly higher objective response rate (68% vs. 45%; P less than .0001) and more complete responses (10% vs. 4%) among the 495 patients with unresectable, locally advanced or metastatic BRAF V600 mutation–positive disease.
Overall survival data are not yet mature, but the interim analysis showed a promising 35% reduction in the risk of death at 9 months (HR, 0.65), said Dr. McArthur of the Peter MacCallum Cancer Centre, Melbourne, Australia. The corresponding P value of .046 is descriptive, as it did not cross the prespecified stopping boundary for the interim analysis.
Grade 3 toxicity, albeit fairly common, was slightly higher with combination therapy vs. vemurafenib alone (65% vs. 59%). Adverse event–related treatment discontinuations were similar between arms (13% vs. 12%), he said.
The data, which were simultaneously published in the New England Journal of Medicine (2014 Sept. 29 [doi:10.1056/NEJMoa1408868]) are expected to be submitted to the U.S. Food and Drug Administration later this year for potential approval of cobimetinib. Vemurafenib was approved in the United States for late-stage or unresectable melanoma in August 2011.
In our video interview, Dr. McArthur discusses coBRIM and his suggestions for how clinicians may incorporate this novel strategy into practice.
coBRIM was funded by F. Hoffmann-LaRoche/Genentech. Dr. McArthur reported grants from Roche, Novartis, Pfizer, Millennium, and Celegene, and consulting for Provectus.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Combining the investigational MEK inhibitor cobimetinib with the BRAF inhibitor vemurafenib nearly halved the risk of progression in previously untreated patients with BRAF-mutated advanced melanoma in the ongoing, phase III coBRIM study.
Median progression-free survival by investigator was 6.2 months with vemurafenib (Zelboraf) and 9.9 months with the combination (Hazard ratio 0.51; P less than .0001); by independent review, median progression-free survival was 6.0 months versus 11.3 months, respectively (HR, 0.60; P = .0003), study author Dr. Grant McArthur reported in a late-breaking abstract at the European Society for Medical Oncology Congress.
Combination therapy also resulted in a significantly higher objective response rate (68% vs. 45%; P less than .0001) and more complete responses (10% vs. 4%) among the 495 patients with unresectable, locally advanced or metastatic BRAF V600 mutation–positive disease.
Overall survival data are not yet mature, but the interim analysis showed a promising 35% reduction in the risk of death at 9 months (HR, 0.65), said Dr. McArthur of the Peter MacCallum Cancer Centre, Melbourne, Australia. The corresponding P value of .046 is descriptive, as it did not cross the prespecified stopping boundary for the interim analysis.
Grade 3 toxicity, albeit fairly common, was slightly higher with combination therapy vs. vemurafenib alone (65% vs. 59%). Adverse event–related treatment discontinuations were similar between arms (13% vs. 12%), he said.
The data, which were simultaneously published in the New England Journal of Medicine (2014 Sept. 29 [doi:10.1056/NEJMoa1408868]) are expected to be submitted to the U.S. Food and Drug Administration later this year for potential approval of cobimetinib. Vemurafenib was approved in the United States for late-stage or unresectable melanoma in August 2011.
In our video interview, Dr. McArthur discusses coBRIM and his suggestions for how clinicians may incorporate this novel strategy into practice.
coBRIM was funded by F. Hoffmann-LaRoche/Genentech. Dr. McArthur reported grants from Roche, Novartis, Pfizer, Millennium, and Celegene, and consulting for Provectus.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ESMO 2014
Cancer treatment during pregnancy can be safe
MADRID—Two new studies suggest that children exposed to chemotherapy or radiotherapy in the womb can be spared negative long-term effects.
At a median age of 6, most of the children exposed to radiation in utero had neuropsychological, behavioral, and general health outcomes that were within normal ranges.
And children who were exposed to chemotherapy in the womb had normal mental and cardiac health at a median age of 2.
“When chemotherapy is administered after the first trimester of pregnancy, we cannot discern any problems in the children,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.
“Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother, or to deliver a baby prematurely.”
Dr Amant and his colleagues presented these findings (abstract 267PD_PR) and their findings on radiation (abstract 49LBA_PR) at the ESMO 2014 Congress.
Outcomes with chemotherapy
In the first study, the researchers recruited 38 children from the International Network for Cancer, Infertility and Pregnancy registry who were prenatally exposed to chemotherapy.
Most of the mothers had breast (61%) or hematologic (22%) cancers. Most were treated with anthracyclines (61%) and had received an average of 4 cycles (range, 1-7) of treatment.
The researchers assessed mental development and cardiac health in the children of these subjects, comparing them to 38 control children who were not exposed to chemotherapy.
At a median age of almost 2 years, mental development was in the normal range for both groups of children, and development was not significantly different between the groups. The mean Mental Development Index score was 99.13 for exposed children and 101.47 for controls.
Cardiac dimensions and functions were within normal ranges for both groups as well. Mean fractional shortening was 36% (range, 32-42) for exposed children and 39% (range, 32-51) for controls. Although the difference was signficant (P=0.004), the researchers said it was not clinically relevant.
“This paper points to the very important issue of long-term safety of prenatal exposure to chemotherapy and reinforces the notion that chemotherapy during gestation does not endanger the fetus and her or his subsequent development,” said Fedro Alessandro Peccatori, MD, PhD, of the European Institute of Oncology in Milan, Italy, who was not involved in this study.
“To further ameliorate neonatal outcome, a special effort should be made to prolong pregnancy duration, and stringent long-term follow-up should be pursued to confirm these findings. Meanwhile, specific measures to support prematurely delivered babies and their families should be implemented.”
Dr Amant said future studies will explore the effects of specific chemotherapy types in detail and include longer-term follow-up.
Outcomes with radiation
In a second study, Dr Amant and his colleagues explored the impact of radiotherapy on the children of women with cancer.
The study included 16 children, with a median age of 6 years, who had been exposed to radiotherapy in utero. The median maternal irradiation was 48 Gy (range, 12-70), and the median estimated fetal irradiation was 91 mGy (range, 0-1690).
Neuropsychological, behavioral, and general health outcomes were within normal ranges for most of the children. And the researchers found no linear relationship between the fetal dose of radiation and cognitive outcome.
However, there was a negative linear relationship between the gestational age at radiotherapy exposure and verbal intelligence, based on results in 8 children. Two of these children were exposed to radiotherapy in the third trimester and had verbal intelligence scores outside the normal range.
One of the 2 children had low scores on all variables of cognitive development, but other pregnancy-related complications are confounding factors. The child’s mother suffered from an aggressive non-Hodgkin tumor of the brain that impacted her general state, and she had a preterm delivery.
Dr Amant noted that this is based on a very small number of children, so the results should be interpreted with caution.
“We cannot exclude that there might be an impact of prenatal radiotherapy exposure,” he said, “but larger series are needed to further investigate this relationship.” 
MADRID—Two new studies suggest that children exposed to chemotherapy or radiotherapy in the womb can be spared negative long-term effects.
At a median age of 6, most of the children exposed to radiation in utero had neuropsychological, behavioral, and general health outcomes that were within normal ranges.
And children who were exposed to chemotherapy in the womb had normal mental and cardiac health at a median age of 2.
“When chemotherapy is administered after the first trimester of pregnancy, we cannot discern any problems in the children,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.
“Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother, or to deliver a baby prematurely.”
Dr Amant and his colleagues presented these findings (abstract 267PD_PR) and their findings on radiation (abstract 49LBA_PR) at the ESMO 2014 Congress.
Outcomes with chemotherapy
In the first study, the researchers recruited 38 children from the International Network for Cancer, Infertility and Pregnancy registry who were prenatally exposed to chemotherapy.
Most of the mothers had breast (61%) or hematologic (22%) cancers. Most were treated with anthracyclines (61%) and had received an average of 4 cycles (range, 1-7) of treatment.
The researchers assessed mental development and cardiac health in the children of these subjects, comparing them to 38 control children who were not exposed to chemotherapy.
At a median age of almost 2 years, mental development was in the normal range for both groups of children, and development was not significantly different between the groups. The mean Mental Development Index score was 99.13 for exposed children and 101.47 for controls.
Cardiac dimensions and functions were within normal ranges for both groups as well. Mean fractional shortening was 36% (range, 32-42) for exposed children and 39% (range, 32-51) for controls. Although the difference was signficant (P=0.004), the researchers said it was not clinically relevant.
“This paper points to the very important issue of long-term safety of prenatal exposure to chemotherapy and reinforces the notion that chemotherapy during gestation does not endanger the fetus and her or his subsequent development,” said Fedro Alessandro Peccatori, MD, PhD, of the European Institute of Oncology in Milan, Italy, who was not involved in this study.
“To further ameliorate neonatal outcome, a special effort should be made to prolong pregnancy duration, and stringent long-term follow-up should be pursued to confirm these findings. Meanwhile, specific measures to support prematurely delivered babies and their families should be implemented.”
Dr Amant said future studies will explore the effects of specific chemotherapy types in detail and include longer-term follow-up.
Outcomes with radiation
In a second study, Dr Amant and his colleagues explored the impact of radiotherapy on the children of women with cancer.
The study included 16 children, with a median age of 6 years, who had been exposed to radiotherapy in utero. The median maternal irradiation was 48 Gy (range, 12-70), and the median estimated fetal irradiation was 91 mGy (range, 0-1690).
Neuropsychological, behavioral, and general health outcomes were within normal ranges for most of the children. And the researchers found no linear relationship between the fetal dose of radiation and cognitive outcome.
However, there was a negative linear relationship between the gestational age at radiotherapy exposure and verbal intelligence, based on results in 8 children. Two of these children were exposed to radiotherapy in the third trimester and had verbal intelligence scores outside the normal range.
One of the 2 children had low scores on all variables of cognitive development, but other pregnancy-related complications are confounding factors. The child’s mother suffered from an aggressive non-Hodgkin tumor of the brain that impacted her general state, and she had a preterm delivery.
Dr Amant noted that this is based on a very small number of children, so the results should be interpreted with caution.
“We cannot exclude that there might be an impact of prenatal radiotherapy exposure,” he said, “but larger series are needed to further investigate this relationship.”
MADRID—Two new studies suggest that children exposed to chemotherapy or radiotherapy in the womb can be spared negative long-term effects.
At a median age of 6, most of the children exposed to radiation in utero had neuropsychological, behavioral, and general health outcomes that were within normal ranges.
And children who were exposed to chemotherapy in the womb had normal mental and cardiac health at a median age of 2.
“When chemotherapy is administered after the first trimester of pregnancy, we cannot discern any problems in the children,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.
“Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother, or to deliver a baby prematurely.”
Dr Amant and his colleagues presented these findings (abstract 267PD_PR) and their findings on radiation (abstract 49LBA_PR) at the ESMO 2014 Congress.
Outcomes with chemotherapy
In the first study, the researchers recruited 38 children from the International Network for Cancer, Infertility and Pregnancy registry who were prenatally exposed to chemotherapy.
Most of the mothers had breast (61%) or hematologic (22%) cancers. Most were treated with anthracyclines (61%) and had received an average of 4 cycles (range, 1-7) of treatment.
The researchers assessed mental development and cardiac health in the children of these subjects, comparing them to 38 control children who were not exposed to chemotherapy.
At a median age of almost 2 years, mental development was in the normal range for both groups of children, and development was not significantly different between the groups. The mean Mental Development Index score was 99.13 for exposed children and 101.47 for controls.
Cardiac dimensions and functions were within normal ranges for both groups as well. Mean fractional shortening was 36% (range, 32-42) for exposed children and 39% (range, 32-51) for controls. Although the difference was signficant (P=0.004), the researchers said it was not clinically relevant.
“This paper points to the very important issue of long-term safety of prenatal exposure to chemotherapy and reinforces the notion that chemotherapy during gestation does not endanger the fetus and her or his subsequent development,” said Fedro Alessandro Peccatori, MD, PhD, of the European Institute of Oncology in Milan, Italy, who was not involved in this study.
“To further ameliorate neonatal outcome, a special effort should be made to prolong pregnancy duration, and stringent long-term follow-up should be pursued to confirm these findings. Meanwhile, specific measures to support prematurely delivered babies and their families should be implemented.”
Dr Amant said future studies will explore the effects of specific chemotherapy types in detail and include longer-term follow-up.
Outcomes with radiation
In a second study, Dr Amant and his colleagues explored the impact of radiotherapy on the children of women with cancer.
The study included 16 children, with a median age of 6 years, who had been exposed to radiotherapy in utero. The median maternal irradiation was 48 Gy (range, 12-70), and the median estimated fetal irradiation was 91 mGy (range, 0-1690).
Neuropsychological, behavioral, and general health outcomes were within normal ranges for most of the children. And the researchers found no linear relationship between the fetal dose of radiation and cognitive outcome.
However, there was a negative linear relationship between the gestational age at radiotherapy exposure and verbal intelligence, based on results in 8 children. Two of these children were exposed to radiotherapy in the third trimester and had verbal intelligence scores outside the normal range.
One of the 2 children had low scores on all variables of cognitive development, but other pregnancy-related complications are confounding factors. The child’s mother suffered from an aggressive non-Hodgkin tumor of the brain that impacted her general state, and she had a preterm delivery.
Dr Amant noted that this is based on a very small number of children, so the results should be interpreted with caution.
“We cannot exclude that there might be an impact of prenatal radiotherapy exposure,” he said, “but larger series are needed to further investigate this relationship.”
AUDIO: Hope Rugo reviews pivotal breast cancer trials at ESMO
MADRID – From CLEOPATRA to IMELDA and TANIA, Dr. Hope S. Rugo shared her insights on these three breast cancer trials and more making headlines at the European Society for Medical Oncology Congress.
The final overall survival analysis from the phase III CLEOPATRA trial is certainly the blockbuster in breast cancer at the meeting in Madrid, establishing a new treatment regimen of dual targeted therapy plus chemotherapy in first-line HER2-positive metastatic disease.
Other breast cancer trials, such as IMELDA, TANIA, and RESILIENCE, provide a mixture of thought-provoking results for practicing oncologists, according to Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco.
Dr. Rugo reported financial relationships with Genomic Health, Merck, Novartis, and Plexxikon.
MADRID – From CLEOPATRA to IMELDA and TANIA, Dr. Hope S. Rugo shared her insights on these three breast cancer trials and more making headlines at the European Society for Medical Oncology Congress.
The final overall survival analysis from the phase III CLEOPATRA trial is certainly the blockbuster in breast cancer at the meeting in Madrid, establishing a new treatment regimen of dual targeted therapy plus chemotherapy in first-line HER2-positive metastatic disease.
Other breast cancer trials, such as IMELDA, TANIA, and RESILIENCE, provide a mixture of thought-provoking results for practicing oncologists, according to Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco.
Dr. Rugo reported financial relationships with Genomic Health, Merck, Novartis, and Plexxikon.
MADRID – From CLEOPATRA to IMELDA and TANIA, Dr. Hope S. Rugo shared her insights on these three breast cancer trials and more making headlines at the European Society for Medical Oncology Congress.
The final overall survival analysis from the phase III CLEOPATRA trial is certainly the blockbuster in breast cancer at the meeting in Madrid, establishing a new treatment regimen of dual targeted therapy plus chemotherapy in first-line HER2-positive metastatic disease.
Other breast cancer trials, such as IMELDA, TANIA, and RESILIENCE, provide a mixture of thought-provoking results for practicing oncologists, according to Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco.
Dr. Rugo reported financial relationships with Genomic Health, Merck, Novartis, and Plexxikon.
AT ESMO 2014
VIDEO: CLEOPATRA combo extends survival in HER2-positive metastatic breast cancer
MADRID – The final overall survival analysis of the CLEOPATRA trial showed an unprecedented 15.7-month increase in overall survival for women with HER2-positive metastatic breast cancer.
The results were achieved by adding pertuzumab to first-line trastuzumab and docetaxel chemotherapy (56.5 months vs. 40.8 months; hazard ratio, 0.68; P = .0002).
Importantly, the survival improvement came without excessive toxicity, including cardiac events, lead author Dr. Sandra Swain reported during a presidential symposium at the European Society for Medical Oncology Congress.
The results, now with a median follow-up of 50 months, build on those previously reported from CLEOPATRA, showing a survival trend favoring the combination of two targeted agents with chemotherapy in the first interim analysis and a statistically significant overall survival advantage at 30 months in a second interim analysis.
In a video interview at the meeting, Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center, discusses the results and their implications for care.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – The final overall survival analysis of the CLEOPATRA trial showed an unprecedented 15.7-month increase in overall survival for women with HER2-positive metastatic breast cancer.
The results were achieved by adding pertuzumab to first-line trastuzumab and docetaxel chemotherapy (56.5 months vs. 40.8 months; hazard ratio, 0.68; P = .0002).
Importantly, the survival improvement came without excessive toxicity, including cardiac events, lead author Dr. Sandra Swain reported during a presidential symposium at the European Society for Medical Oncology Congress.
The results, now with a median follow-up of 50 months, build on those previously reported from CLEOPATRA, showing a survival trend favoring the combination of two targeted agents with chemotherapy in the first interim analysis and a statistically significant overall survival advantage at 30 months in a second interim analysis.
In a video interview at the meeting, Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center, discusses the results and their implications for care.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – The final overall survival analysis of the CLEOPATRA trial showed an unprecedented 15.7-month increase in overall survival for women with HER2-positive metastatic breast cancer.
The results were achieved by adding pertuzumab to first-line trastuzumab and docetaxel chemotherapy (56.5 months vs. 40.8 months; hazard ratio, 0.68; P = .0002).
Importantly, the survival improvement came without excessive toxicity, including cardiac events, lead author Dr. Sandra Swain reported during a presidential symposium at the European Society for Medical Oncology Congress.
The results, now with a median follow-up of 50 months, build on those previously reported from CLEOPATRA, showing a survival trend favoring the combination of two targeted agents with chemotherapy in the first interim analysis and a statistically significant overall survival advantage at 30 months in a second interim analysis.
In a video interview at the meeting, Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center, discusses the results and their implications for care.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ESMO 2014
Key clinical point: CLEOPATRA establishes pertuzumab and trastuzumab plus chemotherapy as the standard of care in metastatic HER2-positive breast cancer.
Major finding: Overall survival was 40.8 months with trastuzumab plus chemotherapy, and 56.5 months with the addition of pertuzumab.
Data source: Phase III double-blind trial in 808 women with HER2-positive metastatic breast cancer.
Disclosures: The study was funded by Hoffman-La Roche, Genentech. Dr. Swain reported serving as an uncompensated consultant for Genentech/Roche. Her institution has received research funding from Genentech/Roche, Pfizer, Puma, Sanofi-Aventis, and Bristol-Myers Squibb. Several of her coauthors reported financial relationships with several drug firms.
Combo shows potential as frontline therapy in PTCL
Credit: NIH
MADRID—Follow-up data from a phase 1 trial suggest brentuximab vedotin plus chemotherapy may be a feasible frontline option for patients with peripheral T-cell lymphoma (PTCL).
At the ESMO 2014 Congress, investigators presented a 2-year durability analysis from a trial of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV+CHP) in patients newly diagnosed with PTCL.
The estimated 2-year overall survival rate was 80% in these patients. And the median progression-free survival was not reached.
Michelle Fanale, MD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these results as abstract 944O.
The research was sponsored by Seattle Genetics Inc. and Takeda Pharmaceuticals International, the companies co-developing brentuximab vedotin (Adcetris).
In this trial, patients received 1 of 2 treatment regimens. The first was sequential treatment (once every 3 weeks) with brentuximab vedotin at 1.8 mg/kg for 2 cycles, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for 6 cycles.
The second was combination BV+CHP every 3 weeks for 6 cycles. Patients who achieved at least a partial response after 6 cycles of treatment were eligible to receive continued single-agent brentuximab vedotin for up to 10 additional 3-week cycles.
Earlier results with both treatment regimens were published in the Journal of Clinical Oncology. At ESMO, Dr Fanale presented 2-year results among the 26 patients who received BV+CHP.
The median patient age was 56 years. Nineteen patients had systemic anaplastic large-cell lymphoma (sALCL), including 16 patients (62%) with ALK-negative disease.
Two patients had PTCL not otherwise specified, 2 had angioimmunoblastic T-cell lymphoma, 2 had adult T-cell leukemia/lymphoma, and 1 had enteropathy-associated T-cell lymphoma. The majority of patients had advanced-stage disease and/or were considered high risk.
All 26 patients had an objective response to BV+CHP, including 23 patients (88%) with a complete response. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET.
The median observation time was 27.1 months from the first dose of therapy. The estimated 2-year progression-free survival rate was 54%, with no patients receiving a consolidative stem cell transplant. And the estimated 2-year overall survival rate was 80%.
The most common treatment-emergent adverse events of any grade occurring in more than 40% of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea, and shortness of breath.
Based on the results of this study, Seattle Genetics and Takeda initiated a global phase 3 study called ECHELON-2. This randomized, double-blind, placebo-controlled, multicenter trial was designed to investigate BV+CHP vs CHOP as frontline therapy in patients with CD30-positive PTCL.
The study is currently enrolling patients. It is expected to enroll 300 patients, who will be randomized to receive either treatment every 3 weeks for 6 to 8 cycles. 
Credit: NIH
MADRID—Follow-up data from a phase 1 trial suggest brentuximab vedotin plus chemotherapy may be a feasible frontline option for patients with peripheral T-cell lymphoma (PTCL).
At the ESMO 2014 Congress, investigators presented a 2-year durability analysis from a trial of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV+CHP) in patients newly diagnosed with PTCL.
The estimated 2-year overall survival rate was 80% in these patients. And the median progression-free survival was not reached.
Michelle Fanale, MD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these results as abstract 944O.
The research was sponsored by Seattle Genetics Inc. and Takeda Pharmaceuticals International, the companies co-developing brentuximab vedotin (Adcetris).
In this trial, patients received 1 of 2 treatment regimens. The first was sequential treatment (once every 3 weeks) with brentuximab vedotin at 1.8 mg/kg for 2 cycles, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for 6 cycles.
The second was combination BV+CHP every 3 weeks for 6 cycles. Patients who achieved at least a partial response after 6 cycles of treatment were eligible to receive continued single-agent brentuximab vedotin for up to 10 additional 3-week cycles.
Earlier results with both treatment regimens were published in the Journal of Clinical Oncology. At ESMO, Dr Fanale presented 2-year results among the 26 patients who received BV+CHP.
The median patient age was 56 years. Nineteen patients had systemic anaplastic large-cell lymphoma (sALCL), including 16 patients (62%) with ALK-negative disease.
Two patients had PTCL not otherwise specified, 2 had angioimmunoblastic T-cell lymphoma, 2 had adult T-cell leukemia/lymphoma, and 1 had enteropathy-associated T-cell lymphoma. The majority of patients had advanced-stage disease and/or were considered high risk.
All 26 patients had an objective response to BV+CHP, including 23 patients (88%) with a complete response. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET.
The median observation time was 27.1 months from the first dose of therapy. The estimated 2-year progression-free survival rate was 54%, with no patients receiving a consolidative stem cell transplant. And the estimated 2-year overall survival rate was 80%.
The most common treatment-emergent adverse events of any grade occurring in more than 40% of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea, and shortness of breath.
Based on the results of this study, Seattle Genetics and Takeda initiated a global phase 3 study called ECHELON-2. This randomized, double-blind, placebo-controlled, multicenter trial was designed to investigate BV+CHP vs CHOP as frontline therapy in patients with CD30-positive PTCL.
The study is currently enrolling patients. It is expected to enroll 300 patients, who will be randomized to receive either treatment every 3 weeks for 6 to 8 cycles.
Credit: NIH
MADRID—Follow-up data from a phase 1 trial suggest brentuximab vedotin plus chemotherapy may be a feasible frontline option for patients with peripheral T-cell lymphoma (PTCL).
At the ESMO 2014 Congress, investigators presented a 2-year durability analysis from a trial of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV+CHP) in patients newly diagnosed with PTCL.
The estimated 2-year overall survival rate was 80% in these patients. And the median progression-free survival was not reached.
Michelle Fanale, MD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these results as abstract 944O.
The research was sponsored by Seattle Genetics Inc. and Takeda Pharmaceuticals International, the companies co-developing brentuximab vedotin (Adcetris).
In this trial, patients received 1 of 2 treatment regimens. The first was sequential treatment (once every 3 weeks) with brentuximab vedotin at 1.8 mg/kg for 2 cycles, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for 6 cycles.
The second was combination BV+CHP every 3 weeks for 6 cycles. Patients who achieved at least a partial response after 6 cycles of treatment were eligible to receive continued single-agent brentuximab vedotin for up to 10 additional 3-week cycles.
Earlier results with both treatment regimens were published in the Journal of Clinical Oncology. At ESMO, Dr Fanale presented 2-year results among the 26 patients who received BV+CHP.
The median patient age was 56 years. Nineteen patients had systemic anaplastic large-cell lymphoma (sALCL), including 16 patients (62%) with ALK-negative disease.
Two patients had PTCL not otherwise specified, 2 had angioimmunoblastic T-cell lymphoma, 2 had adult T-cell leukemia/lymphoma, and 1 had enteropathy-associated T-cell lymphoma. The majority of patients had advanced-stage disease and/or were considered high risk.
All 26 patients had an objective response to BV+CHP, including 23 patients (88%) with a complete response. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET.
The median observation time was 27.1 months from the first dose of therapy. The estimated 2-year progression-free survival rate was 54%, with no patients receiving a consolidative stem cell transplant. And the estimated 2-year overall survival rate was 80%.
The most common treatment-emergent adverse events of any grade occurring in more than 40% of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea, and shortness of breath.
Based on the results of this study, Seattle Genetics and Takeda initiated a global phase 3 study called ECHELON-2. This randomized, double-blind, placebo-controlled, multicenter trial was designed to investigate BV+CHP vs CHOP as frontline therapy in patients with CD30-positive PTCL.
The study is currently enrolling patients. It is expected to enroll 300 patients, who will be randomized to receive either treatment every 3 weeks for 6 to 8 cycles.
Drug can prevent chemo-induced nausea, vomiting
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Rivaroxaban rivals standard for VTE in cancer
Credit: CDC
MADRID—A pooled analysis of 2 studies suggests rivaroxaban prevents recurrent venous thromboembolism (VTE) in cancer patients as effectively as standard therapy, while conferring a lower risk of major bleeding.
The analysis included data from the EINSTEIN-DVT and EINSTEIN-PE trials, which were funded by the companies developing rivaroxaban (Xarelto), Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
The results were published in Lancet Haematology and presented at the ESMO 2014 Congress (abstract LBA48).
The EINSTEIN-PE study included 3449 subjects with acute symptomatic pulmonary embolism (PE), with or without symptomatic deep vein thrombosis (DVT), who received anticoagulant therapy for 6 or 12 months.
The EINSTEIN-DVT study included 4833 patients who had acute symptomatic DVT, but no symptoms of PE, and received treatment for 3, 6, or 12 months.
In both studies, patients received either oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or standard therapy—enoxaparin (1.0 mg/kg twice daily) followed by a vitamin K antagonist (warfarin or acenocoumarol).
A total of 8281 patients were randomized in these studies—4150 to rivaroxaban and 4131 to standard therapy. Of the 655 patients (7.9%) with active cancer, 462 (5.6%) had cancer at baseline, and 193 (2.3%) were diagnosed during the study.
For this analysis, Martin H. Prins, MD, PhD, of Maastricht University Medical Center in The Netherlands, and his colleagues compared the 2 treatments in patients with active cancer.
VTE recurred in 4.5% (16/354) of the patients who were randomized to rivaroxaban and 6.6% (20/301) of patients randomized to standard therapy (hazard ratio [HR]=0.67).
The mortality rate was 16.4% (58/354) among patients randomized to rivaroxaban and 17.6% (53/301) among those randomized to standard therapy (HR=0.93).
Major bleeding occurred in 2.3% (8/353) of patients who received rivaroxaban and 5% (15/298) who received standard therapy (HR=0.42). And clinically relevant bleeding occurred in 13.6% (48/353) and 16.4% (49/298), respectively (HR=0.80).
Given these results, Dr Prins and his colleagues concluded that rivaroxaban can be considered an alternative to standard therapy in patients with cancer-associated VTE.
The team also said there is a need for a head-to-head comparison of rivaroxaban and long-term low-molecular-weight heparin in this patient population.
Credit: CDC
MADRID—A pooled analysis of 2 studies suggests rivaroxaban prevents recurrent venous thromboembolism (VTE) in cancer patients as effectively as standard therapy, while conferring a lower risk of major bleeding.
The analysis included data from the EINSTEIN-DVT and EINSTEIN-PE trials, which were funded by the companies developing rivaroxaban (Xarelto), Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
The results were published in Lancet Haematology and presented at the ESMO 2014 Congress (abstract LBA48).
The EINSTEIN-PE study included 3449 subjects with acute symptomatic pulmonary embolism (PE), with or without symptomatic deep vein thrombosis (DVT), who received anticoagulant therapy for 6 or 12 months.
The EINSTEIN-DVT study included 4833 patients who had acute symptomatic DVT, but no symptoms of PE, and received treatment for 3, 6, or 12 months.
In both studies, patients received either oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or standard therapy—enoxaparin (1.0 mg/kg twice daily) followed by a vitamin K antagonist (warfarin or acenocoumarol).
A total of 8281 patients were randomized in these studies—4150 to rivaroxaban and 4131 to standard therapy. Of the 655 patients (7.9%) with active cancer, 462 (5.6%) had cancer at baseline, and 193 (2.3%) were diagnosed during the study.
For this analysis, Martin H. Prins, MD, PhD, of Maastricht University Medical Center in The Netherlands, and his colleagues compared the 2 treatments in patients with active cancer.
VTE recurred in 4.5% (16/354) of the patients who were randomized to rivaroxaban and 6.6% (20/301) of patients randomized to standard therapy (hazard ratio [HR]=0.67).
The mortality rate was 16.4% (58/354) among patients randomized to rivaroxaban and 17.6% (53/301) among those randomized to standard therapy (HR=0.93).
Major bleeding occurred in 2.3% (8/353) of patients who received rivaroxaban and 5% (15/298) who received standard therapy (HR=0.42). And clinically relevant bleeding occurred in 13.6% (48/353) and 16.4% (49/298), respectively (HR=0.80).
Given these results, Dr Prins and his colleagues concluded that rivaroxaban can be considered an alternative to standard therapy in patients with cancer-associated VTE.
The team also said there is a need for a head-to-head comparison of rivaroxaban and long-term low-molecular-weight heparin in this patient population.
Credit: CDC
MADRID—A pooled analysis of 2 studies suggests rivaroxaban prevents recurrent venous thromboembolism (VTE) in cancer patients as effectively as standard therapy, while conferring a lower risk of major bleeding.
The analysis included data from the EINSTEIN-DVT and EINSTEIN-PE trials, which were funded by the companies developing rivaroxaban (Xarelto), Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
The results were published in Lancet Haematology and presented at the ESMO 2014 Congress (abstract LBA48).
The EINSTEIN-PE study included 3449 subjects with acute symptomatic pulmonary embolism (PE), with or without symptomatic deep vein thrombosis (DVT), who received anticoagulant therapy for 6 or 12 months.
The EINSTEIN-DVT study included 4833 patients who had acute symptomatic DVT, but no symptoms of PE, and received treatment for 3, 6, or 12 months.
In both studies, patients received either oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or standard therapy—enoxaparin (1.0 mg/kg twice daily) followed by a vitamin K antagonist (warfarin or acenocoumarol).
A total of 8281 patients were randomized in these studies—4150 to rivaroxaban and 4131 to standard therapy. Of the 655 patients (7.9%) with active cancer, 462 (5.6%) had cancer at baseline, and 193 (2.3%) were diagnosed during the study.
For this analysis, Martin H. Prins, MD, PhD, of Maastricht University Medical Center in The Netherlands, and his colleagues compared the 2 treatments in patients with active cancer.
VTE recurred in 4.5% (16/354) of the patients who were randomized to rivaroxaban and 6.6% (20/301) of patients randomized to standard therapy (hazard ratio [HR]=0.67).
The mortality rate was 16.4% (58/354) among patients randomized to rivaroxaban and 17.6% (53/301) among those randomized to standard therapy (HR=0.93).
Major bleeding occurred in 2.3% (8/353) of patients who received rivaroxaban and 5% (15/298) who received standard therapy (HR=0.42). And clinically relevant bleeding occurred in 13.6% (48/353) and 16.4% (49/298), respectively (HR=0.80).
Given these results, Dr Prins and his colleagues concluded that rivaroxaban can be considered an alternative to standard therapy in patients with cancer-associated VTE.
The team also said there is a need for a head-to-head comparison of rivaroxaban and long-term low-molecular-weight heparin in this patient population.