SABCS 2018

SAN ANTONIO – For patients with estrogen-receptor positive, HER2-negative metastatic breast cancer, the use of circulating tumor cell (CTC) counts can help clinicians decide with confidence between ordering first-line hormonal therapy or chemotherapy, investigators say.

In the phase 3 STIC CTC trial, patients were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient; or on the CTC count with a cutoff of less than 5 CT/7.5 mL, indicating hormonal therapy; and 5 CTC/7.5 mL or above, indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial met its primary noninferiority endpoint, indicating that, in the overall population, CTC counts can provide clinician’s with confidence in the therapeutic choice, said Francois-Clement Bidard, MD, PhD, from Institut Curie in Paris.

In a video interview, Dr. Bidard discussed the trial findings, including the provocative exploratory analysis suggesting that, in patients in whom there is discordance between CTC and clinician choice, chemotherapy may be a better therapeutic option.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini Silicon Biosystems. Dr. Bidard disclosed research funding and travel grants from Menarini.

SAN ANTONIO – For patients with estrogen-receptor positive, HER2-negative metastatic breast cancer, the use of circulating tumor cell (CTC) counts can help clinicians decide with confidence between ordering first-line hormonal therapy or chemotherapy, investigators say.

In the phase 3 STIC CTC trial, patients were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient; or on the CTC count with a cutoff of less than 5 CT/7.5 mL, indicating hormonal therapy; and 5 CTC/7.5 mL or above, indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial met its primary noninferiority endpoint, indicating that, in the overall population, CTC counts can provide clinician’s with confidence in the therapeutic choice, said Francois-Clement Bidard, MD, PhD, from Institut Curie in Paris.

In a video interview, Dr. Bidard discussed the trial findings, including the provocative exploratory analysis suggesting that, in patients in whom there is discordance between CTC and clinician choice, chemotherapy may be a better therapeutic option.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini Silicon Biosystems. Dr. Bidard disclosed research funding and travel grants from Menarini.

SAN ANTONIO – For patients with estrogen-receptor positive, HER2-negative metastatic breast cancer, the use of circulating tumor cell (CTC) counts can help clinicians decide with confidence between ordering first-line hormonal therapy or chemotherapy, investigators say.

In the phase 3 STIC CTC trial, patients were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient; or on the CTC count with a cutoff of less than 5 CT/7.5 mL, indicating hormonal therapy; and 5 CTC/7.5 mL or above, indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial met its primary noninferiority endpoint, indicating that, in the overall population, CTC counts can provide clinician’s with confidence in the therapeutic choice, said Francois-Clement Bidard, MD, PhD, from Institut Curie in Paris.

In a video interview, Dr. Bidard discussed the trial findings, including the provocative exploratory analysis suggesting that, in patients in whom there is discordance between CTC and clinician choice, chemotherapy may be a better therapeutic option.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini Silicon Biosystems. Dr. Bidard disclosed research funding and travel grants from Menarini.

SAN ANTONIO – Both axillary radiation therapy and axillary lymph node dissection provide excellent, comparable locoregional control in patients with early-stage breast cancer who have a positive sentinel node, according to updated results of the European Organisation for Research and Treatment of Cancer’s AMAROS trial.
 

The 10-year cumulative incidence rate of axillary recurrence was 1.82% with radiation and 0.93% with lymph node dissection, a nonsignificant difference (hazard ratio, 1.71; P = .365). Distant metastasis–free survival and overall survival also were statistically on par. The findings reinforce the trial’s 5-year results, which additionally showed a markedly lower incidence of lymphedema with axillary radiation therapy. Lead investigator Emiel J. T. Rutgers, MD, PhD, reflected on hesitation in the uptake of axillary radiation therapy among oncologists and discussed the AMAROS results in the context of the ACOSOG Z11 trial. Dr. Rutgers, the principal investigator of the AMAROS trial and a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, also described how the trial’s findings have altered practice at his institution.

Dr. Rutgers disclosed that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.

SAN ANTONIO – Both axillary radiation therapy and axillary lymph node dissection provide excellent, comparable locoregional control in patients with early-stage breast cancer who have a positive sentinel node, according to updated results of the European Organisation for Research and Treatment of Cancer’s AMAROS trial.
 

The 10-year cumulative incidence rate of axillary recurrence was 1.82% with radiation and 0.93% with lymph node dissection, a nonsignificant difference (hazard ratio, 1.71; P = .365). Distant metastasis–free survival and overall survival also were statistically on par. The findings reinforce the trial’s 5-year results, which additionally showed a markedly lower incidence of lymphedema with axillary radiation therapy. Lead investigator Emiel J. T. Rutgers, MD, PhD, reflected on hesitation in the uptake of axillary radiation therapy among oncologists and discussed the AMAROS results in the context of the ACOSOG Z11 trial. Dr. Rutgers, the principal investigator of the AMAROS trial and a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, also described how the trial’s findings have altered practice at his institution.

Dr. Rutgers disclosed that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.

SAN ANTONIO – Both axillary radiation therapy and axillary lymph node dissection provide excellent, comparable locoregional control in patients with early-stage breast cancer who have a positive sentinel node, according to updated results of the European Organisation for Research and Treatment of Cancer’s AMAROS trial.
 

The 10-year cumulative incidence rate of axillary recurrence was 1.82% with radiation and 0.93% with lymph node dissection, a nonsignificant difference (hazard ratio, 1.71; P = .365). Distant metastasis–free survival and overall survival also were statistically on par. The findings reinforce the trial’s 5-year results, which additionally showed a markedly lower incidence of lymphedema with axillary radiation therapy. Lead investigator Emiel J. T. Rutgers, MD, PhD, reflected on hesitation in the uptake of axillary radiation therapy among oncologists and discussed the AMAROS results in the context of the ACOSOG Z11 trial. Dr. Rutgers, the principal investigator of the AMAROS trial and a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, also described how the trial’s findings have altered practice at his institution.

Dr. Rutgers disclosed that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may have little to gain from subsequent adjuvant chemotherapy except toxicity, according to a patient-level meta-analysis of more than 27,000 women. The analysis, reported by lead investigator Laura M. Spring, MD, at the San Antonio Breast Cancer Symposium, confirmed that, compared with residual disease, pCR was associated with significantly reduced risks of event-free survival events (hazard ratio, 0.31) and death (HR, 0.22). Moreover, the EFS benefit of a pCR was similar whether women went on to receive adjuvant chemotherapy (HR, 0.36) or not (HR, 0.36) (P = .60 for difference). Dr. Spring discussed overall and subgroup findings, implications for use of neoadjuvant chemotherapy, and how these new data may inform escalation and de-escalation of adjuvant therapy.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
 

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may have little to gain from subsequent adjuvant chemotherapy except toxicity, according to a patient-level meta-analysis of more than 27,000 women. The analysis, reported by lead investigator Laura M. Spring, MD, at the San Antonio Breast Cancer Symposium, confirmed that, compared with residual disease, pCR was associated with significantly reduced risks of event-free survival events (hazard ratio, 0.31) and death (HR, 0.22). Moreover, the EFS benefit of a pCR was similar whether women went on to receive adjuvant chemotherapy (HR, 0.36) or not (HR, 0.36) (P = .60 for difference). Dr. Spring discussed overall and subgroup findings, implications for use of neoadjuvant chemotherapy, and how these new data may inform escalation and de-escalation of adjuvant therapy.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
 

SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may have little to gain from subsequent adjuvant chemotherapy except toxicity, according to a patient-level meta-analysis of more than 27,000 women. The analysis, reported by lead investigator Laura M. Spring, MD, at the San Antonio Breast Cancer Symposium, confirmed that, compared with residual disease, pCR was associated with significantly reduced risks of event-free survival events (hazard ratio, 0.31) and death (HR, 0.22). Moreover, the EFS benefit of a pCR was similar whether women went on to receive adjuvant chemotherapy (HR, 0.36) or not (HR, 0.36) (P = .60 for difference). Dr. Spring discussed overall and subgroup findings, implications for use of neoadjuvant chemotherapy, and how these new data may inform escalation and de-escalation of adjuvant therapy.

Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
 

SAN ANTONIO – A phase 3 randomized NRG Oncology trial (NSABP B-39/RTOG 0413) was unable to rule out the possibility that, after lumpectomy, partial breast irradiation is inferior to whole breast irradiation when it comes to the ipsilateral breast tumor recurrences (invasive disease or ductal carcinoma in situ), reported Frank Vicini, MD, of MHP Radiation Oncology Institute, Pontiac, Mich.
 

The hazard ratio for this event with the former versus latter modality was 1.22, with the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5). However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was just 0.7% (4.6% vs. 3.9%). In a video interview, Dr. Vicini discussed whether this difference is clinically important, and the implications of the trial’s findings, taken together, for offering partial breast irradiation to patients.

Dr. Vicini disclosed that he is a research adviser for ImpediMed. The study was sponsored by the National Cancer Institute.

SAN ANTONIO – A phase 3 randomized NRG Oncology trial (NSABP B-39/RTOG 0413) was unable to rule out the possibility that, after lumpectomy, partial breast irradiation is inferior to whole breast irradiation when it comes to the ipsilateral breast tumor recurrences (invasive disease or ductal carcinoma in situ), reported Frank Vicini, MD, of MHP Radiation Oncology Institute, Pontiac, Mich.
 

The hazard ratio for this event with the former versus latter modality was 1.22, with the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5). However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was just 0.7% (4.6% vs. 3.9%). In a video interview, Dr. Vicini discussed whether this difference is clinically important, and the implications of the trial’s findings, taken together, for offering partial breast irradiation to patients.

Dr. Vicini disclosed that he is a research adviser for ImpediMed. The study was sponsored by the National Cancer Institute.

SAN ANTONIO – A phase 3 randomized NRG Oncology trial (NSABP B-39/RTOG 0413) was unable to rule out the possibility that, after lumpectomy, partial breast irradiation is inferior to whole breast irradiation when it comes to the ipsilateral breast tumor recurrences (invasive disease or ductal carcinoma in situ), reported Frank Vicini, MD, of MHP Radiation Oncology Institute, Pontiac, Mich.
 

The hazard ratio for this event with the former versus latter modality was 1.22, with the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5). However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was just 0.7% (4.6% vs. 3.9%). In a video interview, Dr. Vicini discussed whether this difference is clinically important, and the implications of the trial’s findings, taken together, for offering partial breast irradiation to patients.

Dr. Vicini disclosed that he is a research adviser for ImpediMed. The study was sponsored by the National Cancer Institute.

SAN ANTONIO – New life for old medicine: Women aged under 75 years with breast intraepithelial neoplasms (IEN) who took tamoxifen for 3 years at a dose of 5 mg per day – one-fourth the standard dose – had a 50% reduction in risk of IEN recurrence and an even more remarkable 75% reduction in the risk of contralateral breast cancer, compared with women who took placebos in the TAMO1 study.

Despite concerns about the known side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis/pulmonary embolism between groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen, reported Dr. Andrea De Censi, MD, from Ospedali Galliera in Genoa, Italy.

In a video interview, Dr. De Censi discusses how tamoxifen, a decades-old, inexpensive drug still offers real clinical benefit in day-to-day practice for patients with IEN.

The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest.

SAN ANTONIO – New life for old medicine: Women aged under 75 years with breast intraepithelial neoplasms (IEN) who took tamoxifen for 3 years at a dose of 5 mg per day – one-fourth the standard dose – had a 50% reduction in risk of IEN recurrence and an even more remarkable 75% reduction in the risk of contralateral breast cancer, compared with women who took placebos in the TAMO1 study.

Despite concerns about the known side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis/pulmonary embolism between groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen, reported Dr. Andrea De Censi, MD, from Ospedali Galliera in Genoa, Italy.

In a video interview, Dr. De Censi discusses how tamoxifen, a decades-old, inexpensive drug still offers real clinical benefit in day-to-day practice for patients with IEN.

The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest.

SAN ANTONIO – New life for old medicine: Women aged under 75 years with breast intraepithelial neoplasms (IEN) who took tamoxifen for 3 years at a dose of 5 mg per day – one-fourth the standard dose – had a 50% reduction in risk of IEN recurrence and an even more remarkable 75% reduction in the risk of contralateral breast cancer, compared with women who took placebos in the TAMO1 study.

Despite concerns about the known side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis/pulmonary embolism between groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen, reported Dr. Andrea De Censi, MD, from Ospedali Galliera in Genoa, Italy.

In a video interview, Dr. De Censi discusses how tamoxifen, a decades-old, inexpensive drug still offers real clinical benefit in day-to-day practice for patients with IEN.

The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest.

SAN ANTONIO – Adjuvant capecitabine does not improve outcomes in women with early-stage triple-negative breast cancer (TNBC) who have undergone resection and received standard chemotherapy, finds a phase 3, randomized, controlled trial jointly conducted by the Spanish GEICAM group and the Central and South American CIBOMA group. But the story may not end there.

Susan London/MDedge News

Findings reported in a session and press conference at the San Antonio Breast Cancer Symposium showed that, compared with observation, eight cycles of adjuvant capecitabine (Xeloda) reduced the 5-year risks of disease-free survival events and death by a nonsignificant relative 18% and 8%, respectively, among all 876 women randomized. However, the subgroup whose tumors had the nonbasal phenotype saw large significant benefits, with 47% and 58% relative reductions in these risks, respectively.

“The trial is formally negative,” commented lead investigator Miguel Martín, MD, PhD, head of the medical oncology service at Hospital Gregorio Marañón in Madrid. However, the observation arm fared better than expected. In addition, the trial had a very low–risk patient population, which may help explain why its findings differ somewhat from the more positive findings of the similar CREATE-X trial.

“Our data don’t speak against the CREATE-X study. My personal view is that capecitabine is useful for some TNBC patients,” Dr. Martin said. “Our study is not finished because we are going to look at the genomic characteristics of this group defined as non–basal-like because we want to know more about this subgroup. We are planning also to reproduce our subset in the CREATE-X trial to see if this is a real finding because we are in the era of personalized medicine.”

TNBC is a broad group defined only by negative findings for the main markers having available treatments, he elaborated. “So if we could define a subpopulation that actually benefited from capecitabine, this will be great for the patients.” Currently, conventional pathology does not routinely report on tumor basal phenotype, so all TNBC patients receive the same drugs. “This is a mistake. We should select the right drug for the right patient. Probably not all breast cancer patients are sensitive to the same drugs. But the fact is that we don’t have funding to run trials looking at that because this kind of trial is not interesting for pharma companies.”

Susan London/MDedge News

“That’s an important message that triple-negative is really a big, very heterogeneous group,” agreed SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of oncology programs at the University of Texas, Dallas.

Patients and clinicians alike are largely unaware of the presence of TNBC basal and nonbasal subtypes and their potential importance, he said. “We all need some education on that, us included. It’s a very, very heterogeneous group, it is one that is very challenging. We need to start by educating all of us that there is a need to do research on that. ... We have a duty to define this phenotype better.”

Study details

“TNBC is sensitive to chemotherapy, but a significant proportion of patients will eventually relapse after conventional anthracycline and taxane combinations, so we need new approaches to this population,” Dr. Martín noted.

The trial, joint GEICAM/2003-11 and CIBOMA/2004-01, was designed in 2004. Although no information about capecitabine in breast cancer was available at the time, the investigators selected this drug because it is non–cross-resistant with anthracyclines and taxanes.

About 55% of the patients randomized had node-negative disease and roughly 80% received adjuvant chemotherapy alone because neoadjuvant chemotherapy was generally not used 14 years ago, Dr. Martín noted.

After a median follow-up of 7.34 years, the 5-year disease-free survival rate—the trial’s primary endpoint—was 79.6% with capecitabine and 76.8% with observation, a nonsignificant difference in both unadjusted analysis (hazard ratio, 0.82; P = .136) and adjusted analysis (HR, 0.79; P = .082). The 5-year overall survival rate was 86.2% with capecitabine and 85.9% with observation, another nonsignificant difference (HR, 0.92; P = .623).

However, in subgroup analyses among the 248 patients with nonbasal disease, defined as immunohistochemically negative for both EGFR and CK5/6, capecitabine conferred a significant disease-free survival advantage (HR, 0.53; P = .02) and overall survival advantage (HR, 0.420; P = .007) relative to observation.

Interaction of basal/nonbasal phenotype with treatment was marginal for disease-free survival (P = .0694) and significant for overall survival (P = .0052).

In the nonbasal subgroup, the disease-free survival benefit of capecitabine was mainly driven by a reduction in distant recurrences, particularly in the liver and the brain.

Adjuvant capecitabine had tolerability that was “exactly as expected,” according to Dr. Martín. The median dose intensity was 86.3%, and 75.2% of patients completed all of the planned eight cycles.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín reported receiving speaker’s honoraria from Pfizer and Eli Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Eli Lilly; and research grants from Novartis and Roche.

SOURCE: Martín M et al. SABCS 2018, Abstract GS2-04.

SAN ANTONIO – Adjuvant capecitabine does not improve outcomes in women with early-stage triple-negative breast cancer (TNBC) who have undergone resection and received standard chemotherapy, finds a phase 3, randomized, controlled trial jointly conducted by the Spanish GEICAM group and the Central and South American CIBOMA group. But the story may not end there.

Susan London/MDedge News

Findings reported in a session and press conference at the San Antonio Breast Cancer Symposium showed that, compared with observation, eight cycles of adjuvant capecitabine (Xeloda) reduced the 5-year risks of disease-free survival events and death by a nonsignificant relative 18% and 8%, respectively, among all 876 women randomized. However, the subgroup whose tumors had the nonbasal phenotype saw large significant benefits, with 47% and 58% relative reductions in these risks, respectively.

“The trial is formally negative,” commented lead investigator Miguel Martín, MD, PhD, head of the medical oncology service at Hospital Gregorio Marañón in Madrid. However, the observation arm fared better than expected. In addition, the trial had a very low–risk patient population, which may help explain why its findings differ somewhat from the more positive findings of the similar CREATE-X trial.

“Our data don’t speak against the CREATE-X study. My personal view is that capecitabine is useful for some TNBC patients,” Dr. Martin said. “Our study is not finished because we are going to look at the genomic characteristics of this group defined as non–basal-like because we want to know more about this subgroup. We are planning also to reproduce our subset in the CREATE-X trial to see if this is a real finding because we are in the era of personalized medicine.”

TNBC is a broad group defined only by negative findings for the main markers having available treatments, he elaborated. “So if we could define a subpopulation that actually benefited from capecitabine, this will be great for the patients.” Currently, conventional pathology does not routinely report on tumor basal phenotype, so all TNBC patients receive the same drugs. “This is a mistake. We should select the right drug for the right patient. Probably not all breast cancer patients are sensitive to the same drugs. But the fact is that we don’t have funding to run trials looking at that because this kind of trial is not interesting for pharma companies.”

Susan London/MDedge News

“That’s an important message that triple-negative is really a big, very heterogeneous group,” agreed SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of oncology programs at the University of Texas, Dallas.

Patients and clinicians alike are largely unaware of the presence of TNBC basal and nonbasal subtypes and their potential importance, he said. “We all need some education on that, us included. It’s a very, very heterogeneous group, it is one that is very challenging. We need to start by educating all of us that there is a need to do research on that. ... We have a duty to define this phenotype better.”

Study details

“TNBC is sensitive to chemotherapy, but a significant proportion of patients will eventually relapse after conventional anthracycline and taxane combinations, so we need new approaches to this population,” Dr. Martín noted.

The trial, joint GEICAM/2003-11 and CIBOMA/2004-01, was designed in 2004. Although no information about capecitabine in breast cancer was available at the time, the investigators selected this drug because it is non–cross-resistant with anthracyclines and taxanes.

About 55% of the patients randomized had node-negative disease and roughly 80% received adjuvant chemotherapy alone because neoadjuvant chemotherapy was generally not used 14 years ago, Dr. Martín noted.

After a median follow-up of 7.34 years, the 5-year disease-free survival rate—the trial’s primary endpoint—was 79.6% with capecitabine and 76.8% with observation, a nonsignificant difference in both unadjusted analysis (hazard ratio, 0.82; P = .136) and adjusted analysis (HR, 0.79; P = .082). The 5-year overall survival rate was 86.2% with capecitabine and 85.9% with observation, another nonsignificant difference (HR, 0.92; P = .623).

However, in subgroup analyses among the 248 patients with nonbasal disease, defined as immunohistochemically negative for both EGFR and CK5/6, capecitabine conferred a significant disease-free survival advantage (HR, 0.53; P = .02) and overall survival advantage (HR, 0.420; P = .007) relative to observation.

Interaction of basal/nonbasal phenotype with treatment was marginal for disease-free survival (P = .0694) and significant for overall survival (P = .0052).

In the nonbasal subgroup, the disease-free survival benefit of capecitabine was mainly driven by a reduction in distant recurrences, particularly in the liver and the brain.

Adjuvant capecitabine had tolerability that was “exactly as expected,” according to Dr. Martín. The median dose intensity was 86.3%, and 75.2% of patients completed all of the planned eight cycles.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín reported receiving speaker’s honoraria from Pfizer and Eli Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Eli Lilly; and research grants from Novartis and Roche.

SOURCE: Martín M et al. SABCS 2018, Abstract GS2-04.

SAN ANTONIO – Adjuvant capecitabine does not improve outcomes in women with early-stage triple-negative breast cancer (TNBC) who have undergone resection and received standard chemotherapy, finds a phase 3, randomized, controlled trial jointly conducted by the Spanish GEICAM group and the Central and South American CIBOMA group. But the story may not end there.

Susan London/MDedge News

Findings reported in a session and press conference at the San Antonio Breast Cancer Symposium showed that, compared with observation, eight cycles of adjuvant capecitabine (Xeloda) reduced the 5-year risks of disease-free survival events and death by a nonsignificant relative 18% and 8%, respectively, among all 876 women randomized. However, the subgroup whose tumors had the nonbasal phenotype saw large significant benefits, with 47% and 58% relative reductions in these risks, respectively.

“The trial is formally negative,” commented lead investigator Miguel Martín, MD, PhD, head of the medical oncology service at Hospital Gregorio Marañón in Madrid. However, the observation arm fared better than expected. In addition, the trial had a very low–risk patient population, which may help explain why its findings differ somewhat from the more positive findings of the similar CREATE-X trial.

“Our data don’t speak against the CREATE-X study. My personal view is that capecitabine is useful for some TNBC patients,” Dr. Martin said. “Our study is not finished because we are going to look at the genomic characteristics of this group defined as non–basal-like because we want to know more about this subgroup. We are planning also to reproduce our subset in the CREATE-X trial to see if this is a real finding because we are in the era of personalized medicine.”

TNBC is a broad group defined only by negative findings for the main markers having available treatments, he elaborated. “So if we could define a subpopulation that actually benefited from capecitabine, this will be great for the patients.” Currently, conventional pathology does not routinely report on tumor basal phenotype, so all TNBC patients receive the same drugs. “This is a mistake. We should select the right drug for the right patient. Probably not all breast cancer patients are sensitive to the same drugs. But the fact is that we don’t have funding to run trials looking at that because this kind of trial is not interesting for pharma companies.”

Susan London/MDedge News

“That’s an important message that triple-negative is really a big, very heterogeneous group,” agreed SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of oncology programs at the University of Texas, Dallas.

Patients and clinicians alike are largely unaware of the presence of TNBC basal and nonbasal subtypes and their potential importance, he said. “We all need some education on that, us included. It’s a very, very heterogeneous group, it is one that is very challenging. We need to start by educating all of us that there is a need to do research on that. ... We have a duty to define this phenotype better.”

Study details

“TNBC is sensitive to chemotherapy, but a significant proportion of patients will eventually relapse after conventional anthracycline and taxane combinations, so we need new approaches to this population,” Dr. Martín noted.

The trial, joint GEICAM/2003-11 and CIBOMA/2004-01, was designed in 2004. Although no information about capecitabine in breast cancer was available at the time, the investigators selected this drug because it is non–cross-resistant with anthracyclines and taxanes.

About 55% of the patients randomized had node-negative disease and roughly 80% received adjuvant chemotherapy alone because neoadjuvant chemotherapy was generally not used 14 years ago, Dr. Martín noted.

After a median follow-up of 7.34 years, the 5-year disease-free survival rate—the trial’s primary endpoint—was 79.6% with capecitabine and 76.8% with observation, a nonsignificant difference in both unadjusted analysis (hazard ratio, 0.82; P = .136) and adjusted analysis (HR, 0.79; P = .082). The 5-year overall survival rate was 86.2% with capecitabine and 85.9% with observation, another nonsignificant difference (HR, 0.92; P = .623).

However, in subgroup analyses among the 248 patients with nonbasal disease, defined as immunohistochemically negative for both EGFR and CK5/6, capecitabine conferred a significant disease-free survival advantage (HR, 0.53; P = .02) and overall survival advantage (HR, 0.420; P = .007) relative to observation.

Interaction of basal/nonbasal phenotype with treatment was marginal for disease-free survival (P = .0694) and significant for overall survival (P = .0052).

In the nonbasal subgroup, the disease-free survival benefit of capecitabine was mainly driven by a reduction in distant recurrences, particularly in the liver and the brain.

Adjuvant capecitabine had tolerability that was “exactly as expected,” according to Dr. Martín. The median dose intensity was 86.3%, and 75.2% of patients completed all of the planned eight cycles.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín reported receiving speaker’s honoraria from Pfizer and Eli Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Eli Lilly; and research grants from Novartis and Roche.

SOURCE: Martín M et al. SABCS 2018, Abstract GS2-04.

SAN ANTONIO – Patients with HER2-positive early breast cancer with residual invasive disease following neoadjuvant therapy had a 50% reduction in risk for invasive breast cancer recurrence or death when they were treated with the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla), results of the KATHERINE trial showed.

Among 743 patients randomized to adjuvant therapy with T-DM1, the 3-year invasive disease-free survival (IDFS) rate was 88.3%, compared with 77.0% for patients assigned to adjuvant trastuzumab (Herceptin).

The hazard ratio for IDFS – a composite endpoint of freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – was 0.50 (P less than .001), reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond.

“While additional follow-up will be necessary to evaluate the effect of T-DM1 on overall survival, the compelling and consistent efficacy seen on the IDFS endpoint with the safety profile will likely form the foundation of a new standard of care in the KATHERINE patient population,” he said at the San Antonio Breast Cancer Symposium.

Results from KATHERINE were published online in the New England Journal of Medicine to coincide with its presentation in a briefing and in a general session.

KATHERINE was an open-label, phase 3 trial pitting T-DM1 against trastuzumab as adjuvant therapy in patients with early HER2-positive breast cancer with residual invasive disease in the breast or axilla at surgery following neoadjuvant therapy with a taxane (with or without an anthracycline) and trastuzumab. After stratification for clinical presentation (operable vs. inoperable), hormone receptor status, type of preoperative therapy, and pathological nodal status after neoadjuvant, patients were randomized to 14 cycles of either T-DM1 or trastuzumab.

The primary endpoint, IDFS, was as noted before. The trial was stopped after the results were found to cross the efficacy stopping boundary (HR less than 0.732) at the prespecified interim IDFS analysis in July 2018.

The efficacy of T-DM1 was supported by the finding that distant recurrence as the first invasive-disease event occurred in 10.5% of patients assigned to T-DM1, compared with 15.9% of those assigned to trastuzumab. The benefit of T-DM1 was consistent across all key subgroups, including all of the aforementioned stratification factors plus age, group, and race.

The safety analysis included data on 740 patients treated with T-DM1 and 720 treated with trastuzumab. The most common grade 3 or greater adverse events in the T-DM1 group included decreased platelet count in 5.7% and hypertension in 2.0%. The most common grade 3 or greater events in the trastuzumab group were hypertension in 1.2% and radiation-related skin injury in 1.0%.

Serious adverse events were more common in the T-DM1 arm, occurring in 12.7% of patients, compared with 8.1% in the trastuzumab arm. Adverse events leading to discontinuation of the trial drug occurred in 18.0% versus 2.1%, in the T-DM1 arm versus trastuzumab arm respectively.

Dr. Geyer said that, in general, adverse events in the T-DM1 arm were consistent with those seen in other studies, with manageable toxicities and no new safety signals.

“At the present time, the role of T-DM1 in the adjuvant and neoadjuvant setting is limited,” commented invited discussant Eric P. Winer, MD, from the Dana-Farber Cancer Institute in Boston. “It’s confined to patients who have residual disease after neoadjuvant therapy, but I predict this will change dramatically over time. Given how well tolerated T-DM1 is, how effective it was in this study, the answer that one comes to is why not consider using it more broadly and in an earlier-stage setting?”

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, who was not involved in KATHERINE, agreed that the trial results are practice changing.

“I anticipate we would be using T-DM1 in the future for patients who would otherwise have been eligible for KATHERINE,” he said in an interview.

It’s still unclear, however, whether patients who receive pertuzumab (Perjeta) in the neoadjuvant setting and have residual lymph-node positive or estrogen receptor–negative might benefit with adjuvant therapy with T-DM1 instead of trastuzumab, he said.

“The second question that’s unclear at this time is patients who get 1 year of T-DM1, should they then receive neratinib [Nerlynx], because we have data from the ExteNET trial which showed that patients who complete 1 year of anti-HER2 therapy, if they receive 1 year of neratinib, there’s also reduced risk of recurrence, and that’s an unknown question at this time,” Dr. Bardia said.

The trial was funded by Hoffman–La Roche/Genentech. Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene. Dr. Winer reported receiving grants for clinical research from and has served as an adviser or consultant to Genentech, AstraZeneca, Pfizer, and GlaxoSmithKline. Dr. Bardia reported relationships with Genentech and Novartis.

SOURCE: Geyer CE et al. N Engl J Med. 2018 Dec 5. doi: 10.1056/NEJMoa1814017.

SAN ANTONIO – Patients with HER2-positive early breast cancer with residual invasive disease following neoadjuvant therapy had a 50% reduction in risk for invasive breast cancer recurrence or death when they were treated with the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla), results of the KATHERINE trial showed.

Among 743 patients randomized to adjuvant therapy with T-DM1, the 3-year invasive disease-free survival (IDFS) rate was 88.3%, compared with 77.0% for patients assigned to adjuvant trastuzumab (Herceptin).

The hazard ratio for IDFS – a composite endpoint of freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – was 0.50 (P less than .001), reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond.

“While additional follow-up will be necessary to evaluate the effect of T-DM1 on overall survival, the compelling and consistent efficacy seen on the IDFS endpoint with the safety profile will likely form the foundation of a new standard of care in the KATHERINE patient population,” he said at the San Antonio Breast Cancer Symposium.

Results from KATHERINE were published online in the New England Journal of Medicine to coincide with its presentation in a briefing and in a general session.

KATHERINE was an open-label, phase 3 trial pitting T-DM1 against trastuzumab as adjuvant therapy in patients with early HER2-positive breast cancer with residual invasive disease in the breast or axilla at surgery following neoadjuvant therapy with a taxane (with or without an anthracycline) and trastuzumab. After stratification for clinical presentation (operable vs. inoperable), hormone receptor status, type of preoperative therapy, and pathological nodal status after neoadjuvant, patients were randomized to 14 cycles of either T-DM1 or trastuzumab.

The primary endpoint, IDFS, was as noted before. The trial was stopped after the results were found to cross the efficacy stopping boundary (HR less than 0.732) at the prespecified interim IDFS analysis in July 2018.

The efficacy of T-DM1 was supported by the finding that distant recurrence as the first invasive-disease event occurred in 10.5% of patients assigned to T-DM1, compared with 15.9% of those assigned to trastuzumab. The benefit of T-DM1 was consistent across all key subgroups, including all of the aforementioned stratification factors plus age, group, and race.

The safety analysis included data on 740 patients treated with T-DM1 and 720 treated with trastuzumab. The most common grade 3 or greater adverse events in the T-DM1 group included decreased platelet count in 5.7% and hypertension in 2.0%. The most common grade 3 or greater events in the trastuzumab group were hypertension in 1.2% and radiation-related skin injury in 1.0%.

Serious adverse events were more common in the T-DM1 arm, occurring in 12.7% of patients, compared with 8.1% in the trastuzumab arm. Adverse events leading to discontinuation of the trial drug occurred in 18.0% versus 2.1%, in the T-DM1 arm versus trastuzumab arm respectively.

Dr. Geyer said that, in general, adverse events in the T-DM1 arm were consistent with those seen in other studies, with manageable toxicities and no new safety signals.

“At the present time, the role of T-DM1 in the adjuvant and neoadjuvant setting is limited,” commented invited discussant Eric P. Winer, MD, from the Dana-Farber Cancer Institute in Boston. “It’s confined to patients who have residual disease after neoadjuvant therapy, but I predict this will change dramatically over time. Given how well tolerated T-DM1 is, how effective it was in this study, the answer that one comes to is why not consider using it more broadly and in an earlier-stage setting?”

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, who was not involved in KATHERINE, agreed that the trial results are practice changing.

“I anticipate we would be using T-DM1 in the future for patients who would otherwise have been eligible for KATHERINE,” he said in an interview.

It’s still unclear, however, whether patients who receive pertuzumab (Perjeta) in the neoadjuvant setting and have residual lymph-node positive or estrogen receptor–negative might benefit with adjuvant therapy with T-DM1 instead of trastuzumab, he said.

“The second question that’s unclear at this time is patients who get 1 year of T-DM1, should they then receive neratinib [Nerlynx], because we have data from the ExteNET trial which showed that patients who complete 1 year of anti-HER2 therapy, if they receive 1 year of neratinib, there’s also reduced risk of recurrence, and that’s an unknown question at this time,” Dr. Bardia said.

The trial was funded by Hoffman–La Roche/Genentech. Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene. Dr. Winer reported receiving grants for clinical research from and has served as an adviser or consultant to Genentech, AstraZeneca, Pfizer, and GlaxoSmithKline. Dr. Bardia reported relationships with Genentech and Novartis.

SOURCE: Geyer CE et al. N Engl J Med. 2018 Dec 5. doi: 10.1056/NEJMoa1814017.

SAN ANTONIO – Patients with HER2-positive early breast cancer with residual invasive disease following neoadjuvant therapy had a 50% reduction in risk for invasive breast cancer recurrence or death when they were treated with the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla), results of the KATHERINE trial showed.

Among 743 patients randomized to adjuvant therapy with T-DM1, the 3-year invasive disease-free survival (IDFS) rate was 88.3%, compared with 77.0% for patients assigned to adjuvant trastuzumab (Herceptin).

The hazard ratio for IDFS – a composite endpoint of freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – was 0.50 (P less than .001), reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond.

“While additional follow-up will be necessary to evaluate the effect of T-DM1 on overall survival, the compelling and consistent efficacy seen on the IDFS endpoint with the safety profile will likely form the foundation of a new standard of care in the KATHERINE patient population,” he said at the San Antonio Breast Cancer Symposium.

Results from KATHERINE were published online in the New England Journal of Medicine to coincide with its presentation in a briefing and in a general session.

KATHERINE was an open-label, phase 3 trial pitting T-DM1 against trastuzumab as adjuvant therapy in patients with early HER2-positive breast cancer with residual invasive disease in the breast or axilla at surgery following neoadjuvant therapy with a taxane (with or without an anthracycline) and trastuzumab. After stratification for clinical presentation (operable vs. inoperable), hormone receptor status, type of preoperative therapy, and pathological nodal status after neoadjuvant, patients were randomized to 14 cycles of either T-DM1 or trastuzumab.

The primary endpoint, IDFS, was as noted before. The trial was stopped after the results were found to cross the efficacy stopping boundary (HR less than 0.732) at the prespecified interim IDFS analysis in July 2018.

The efficacy of T-DM1 was supported by the finding that distant recurrence as the first invasive-disease event occurred in 10.5% of patients assigned to T-DM1, compared with 15.9% of those assigned to trastuzumab. The benefit of T-DM1 was consistent across all key subgroups, including all of the aforementioned stratification factors plus age, group, and race.

The safety analysis included data on 740 patients treated with T-DM1 and 720 treated with trastuzumab. The most common grade 3 or greater adverse events in the T-DM1 group included decreased platelet count in 5.7% and hypertension in 2.0%. The most common grade 3 or greater events in the trastuzumab group were hypertension in 1.2% and radiation-related skin injury in 1.0%.

Serious adverse events were more common in the T-DM1 arm, occurring in 12.7% of patients, compared with 8.1% in the trastuzumab arm. Adverse events leading to discontinuation of the trial drug occurred in 18.0% versus 2.1%, in the T-DM1 arm versus trastuzumab arm respectively.

Dr. Geyer said that, in general, adverse events in the T-DM1 arm were consistent with those seen in other studies, with manageable toxicities and no new safety signals.

“At the present time, the role of T-DM1 in the adjuvant and neoadjuvant setting is limited,” commented invited discussant Eric P. Winer, MD, from the Dana-Farber Cancer Institute in Boston. “It’s confined to patients who have residual disease after neoadjuvant therapy, but I predict this will change dramatically over time. Given how well tolerated T-DM1 is, how effective it was in this study, the answer that one comes to is why not consider using it more broadly and in an earlier-stage setting?”

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, who was not involved in KATHERINE, agreed that the trial results are practice changing.

“I anticipate we would be using T-DM1 in the future for patients who would otherwise have been eligible for KATHERINE,” he said in an interview.

It’s still unclear, however, whether patients who receive pertuzumab (Perjeta) in the neoadjuvant setting and have residual lymph-node positive or estrogen receptor–negative might benefit with adjuvant therapy with T-DM1 instead of trastuzumab, he said.

“The second question that’s unclear at this time is patients who get 1 year of T-DM1, should they then receive neratinib [Nerlynx], because we have data from the ExteNET trial which showed that patients who complete 1 year of anti-HER2 therapy, if they receive 1 year of neratinib, there’s also reduced risk of recurrence, and that’s an unknown question at this time,” Dr. Bardia said.

The trial was funded by Hoffman–La Roche/Genentech. Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene. Dr. Winer reported receiving grants for clinical research from and has served as an adviser or consultant to Genentech, AstraZeneca, Pfizer, and GlaxoSmithKline. Dr. Bardia reported relationships with Genentech and Novartis.

SOURCE: Geyer CE et al. N Engl J Med. 2018 Dec 5. doi: 10.1056/NEJMoa1814017.

SAN ANTONIO – Programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells is the best predictor of response to atezolizumab + nab-paclitaxel in patients with untreated metastatic triple-negative breast cancer, according to exploratory efficacy analyses of data from the phase 3 IMpassion130 trial.

The analyses of data for the 902 patients randomized to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-palcitaxel for the study also showed consistency between local and central estrogen-receptor, progesterone-receptor, and human epidermal growth factor–receptor 2 testing, Leisha A. Emens, MD, reported at the San Antonio Breast Cancer Symposium.

“IMpassion130 is the first phase 3 study to demonstrate a benefit from [atezolizumab + nab-paclitaxel] in metastatic triple-negative breast cancer (mTNBC),” said Dr. Emens, professor of medicine in hematology/oncology, coleader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center.

She explained that progression-free survival (PFS) was significantly better in PD-L1–positive mTNBC patients treated with the atezolizumab + nab-paclitaxel, than in those who received placebo + nab-paclitaxel (hazard ratios in the intent-to-treat population, 0.8 and 0.62, respectively).

At the first interim overall survival analysis, a clinically meaningful improvement in OS was seen in PD-L1–positive patients in the treatment group (HR, 0.62; median OS improvement from 15.5 months with placebo to 25 months), she added.

In exploratory analyses, Dr. Emens and her colleagues sought to evaluate whether preexisting immune biology is associated with clinical benefit from atezolizumab + nab-paclitaxel, as has been demonstrated in studies of other agents that target the PD-1 pathway in other cancer types of cancer. They also assessed BRCA 1/2 mutation status as a biomarker for response.

“In patients enrolled on the IMpassion130 trial we found that PD-L1 in triple-negative breast cancer was expressed primarily on tumor-infiltrating immune cells,” she said. “In contrast to this, we found a very low rate of PD-L1 expression specifically on tumor cells across the patient population.”

Looking at both of those biomarkers together showed that a majority of patients with expression of PD-L1 on tumor cells were included in the PD-L1 immune cell–positive population, with only 2% having PD-L1 expression exclusively on their tumor cells.

Data previously reported at the European Society for Medical Oncology and published in the New England Journal of Medicine showed a PFS benefit, as well as a clinically meaningful improvement in OS of nearly 10 months, specifically in patients with PD-L1 immune cell–positive lesions treated with atezolizumab + nab-paclitaxel, she noted.

“In data presented for the first time today you can see that PD-L1–negative patients derive no overall survival benefit as there was no treatment effect with this therapy combination,” she said.

A trend was seen toward an association between immune cell positivity and poor prognosis, but this was not statistically significant, she said.

“Taken together, these data definitively show that PD-L1 immune cell positivity is predictive of both progression-free and overall survival benefit with atezolizumab + nab-paclitaxel,” she said.

She and her colleagues also looked at the level of PD-L1 expression in immune cells to assess whether there is a threshold that might be required.

“As long as there was a PD-L1 expression level of 1% or more in the immune cells, there was a significant progression-free and overall survival benefit for patients treated with atezolizumab + nab-paclitaxel. This suggests that this expression of over 1% will represent a threshold for identifying those patients who are likely to benefit from this combination,” she said.

Further assessment by CD8 T-cell status showed that patients who had CD8-positive T cells but who were PD-L1 immune cell negative had no benefit from atezolizumab + nab-paclitaxel, whereas those who were positive for both CD8 and PD-L1 expression on their immune cells derived significant PFS and OS benefit (HR, 0.89 and 0.77, respectively).

“So patients with CD8-positive tumors derive clinical benefit only if their tumors are also PD-L1-positive,” she said.

Similarly, no clinical benefit was seen in patients with stromal tumor-infiltrating lymphocyte (TIL)–positive tumors but who were PD-L1-negative, whereas those with stromal TIL-positive PD-L1–positive tumors derived significant PFS and OS benefit (HRs, 0.99 and 1.53, respectively), and this was also seen in the 15% of evaluable patients who had BRCA mutations.

“In patients who were BRCA mutated, but who were PD-L1 immune cell negative, there was no association of progression-free survival or an overall survival benefit [with atezolizumab + nab-paclitaxel]. In contrast, in patients who were BRCA mutated but PD-L1 immune cell positive ... there was an association with progression-free survival and a trend toward overall survival,” she said, noting that while the BRCA mutation findings are limited by small numbers, “they do show that mutations in BRCA and PD-L1 expression in immune cells are independent biomarkers; patients with BRCA1 or 2 mutations derive clinical benefit only if their tumors are also PD-L1 positive.”

“In this phase 3 IMpassion130 study, PD-L1 expression on immune cells is a predictive biomarker for selecting patients who benefit clinically during first-line treatment with atezolizumab + nab-paclitaxel for metastatic triple-negative breast cancer,” she concluded, adding that “patients with newly diagnosed metastatic and unresectable locally advanced triple-negative breast cancer should be routinely tested for their PD-L1 immune cell status to determine if they might benefit from the combination of atezolizumab + nab-paclitaxel.

IMpassion130 was sponsored by Hoffman-La Roche. Dr. Emens reported receiving royalties and consulting fees from several companies. She has contracts with Roche/Genentech, Corvus, AstraZeneca, and EMD Serono, and ownership in Molecuvax. She receives other support from DSMB and Syndax, and has received grants from Aduro Biotech, Merck, Maxcyte, and the Breast Cancer Research Foundation. She also reported serving as a member of the Food and Drug Administration Advisory Committee on Tissue, Cell, and Gene Therapies, and is a member of the board of directors for the Society of Immunotherapy for Cancer.

SOURCE: Emens L et al. SABCS 2018, Abstract GS1-04.

SAN ANTONIO – Programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells is the best predictor of response to atezolizumab + nab-paclitaxel in patients with untreated metastatic triple-negative breast cancer, according to exploratory efficacy analyses of data from the phase 3 IMpassion130 trial.

The analyses of data for the 902 patients randomized to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-palcitaxel for the study also showed consistency between local and central estrogen-receptor, progesterone-receptor, and human epidermal growth factor–receptor 2 testing, Leisha A. Emens, MD, reported at the San Antonio Breast Cancer Symposium.

“IMpassion130 is the first phase 3 study to demonstrate a benefit from [atezolizumab + nab-paclitaxel] in metastatic triple-negative breast cancer (mTNBC),” said Dr. Emens, professor of medicine in hematology/oncology, coleader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center.

She explained that progression-free survival (PFS) was significantly better in PD-L1–positive mTNBC patients treated with the atezolizumab + nab-paclitaxel, than in those who received placebo + nab-paclitaxel (hazard ratios in the intent-to-treat population, 0.8 and 0.62, respectively).

At the first interim overall survival analysis, a clinically meaningful improvement in OS was seen in PD-L1–positive patients in the treatment group (HR, 0.62; median OS improvement from 15.5 months with placebo to 25 months), she added.

In exploratory analyses, Dr. Emens and her colleagues sought to evaluate whether preexisting immune biology is associated with clinical benefit from atezolizumab + nab-paclitaxel, as has been demonstrated in studies of other agents that target the PD-1 pathway in other cancer types of cancer. They also assessed BRCA 1/2 mutation status as a biomarker for response.

“In patients enrolled on the IMpassion130 trial we found that PD-L1 in triple-negative breast cancer was expressed primarily on tumor-infiltrating immune cells,” she said. “In contrast to this, we found a very low rate of PD-L1 expression specifically on tumor cells across the patient population.”

Looking at both of those biomarkers together showed that a majority of patients with expression of PD-L1 on tumor cells were included in the PD-L1 immune cell–positive population, with only 2% having PD-L1 expression exclusively on their tumor cells.

Data previously reported at the European Society for Medical Oncology and published in the New England Journal of Medicine showed a PFS benefit, as well as a clinically meaningful improvement in OS of nearly 10 months, specifically in patients with PD-L1 immune cell–positive lesions treated with atezolizumab + nab-paclitaxel, she noted.

“In data presented for the first time today you can see that PD-L1–negative patients derive no overall survival benefit as there was no treatment effect with this therapy combination,” she said.

A trend was seen toward an association between immune cell positivity and poor prognosis, but this was not statistically significant, she said.

“Taken together, these data definitively show that PD-L1 immune cell positivity is predictive of both progression-free and overall survival benefit with atezolizumab + nab-paclitaxel,” she said.

She and her colleagues also looked at the level of PD-L1 expression in immune cells to assess whether there is a threshold that might be required.

“As long as there was a PD-L1 expression level of 1% or more in the immune cells, there was a significant progression-free and overall survival benefit for patients treated with atezolizumab + nab-paclitaxel. This suggests that this expression of over 1% will represent a threshold for identifying those patients who are likely to benefit from this combination,” she said.

Further assessment by CD8 T-cell status showed that patients who had CD8-positive T cells but who were PD-L1 immune cell negative had no benefit from atezolizumab + nab-paclitaxel, whereas those who were positive for both CD8 and PD-L1 expression on their immune cells derived significant PFS and OS benefit (HR, 0.89 and 0.77, respectively).

“So patients with CD8-positive tumors derive clinical benefit only if their tumors are also PD-L1-positive,” she said.

Similarly, no clinical benefit was seen in patients with stromal tumor-infiltrating lymphocyte (TIL)–positive tumors but who were PD-L1-negative, whereas those with stromal TIL-positive PD-L1–positive tumors derived significant PFS and OS benefit (HRs, 0.99 and 1.53, respectively), and this was also seen in the 15% of evaluable patients who had BRCA mutations.

“In patients who were BRCA mutated, but who were PD-L1 immune cell negative, there was no association of progression-free survival or an overall survival benefit [with atezolizumab + nab-paclitaxel]. In contrast, in patients who were BRCA mutated but PD-L1 immune cell positive ... there was an association with progression-free survival and a trend toward overall survival,” she said, noting that while the BRCA mutation findings are limited by small numbers, “they do show that mutations in BRCA and PD-L1 expression in immune cells are independent biomarkers; patients with BRCA1 or 2 mutations derive clinical benefit only if their tumors are also PD-L1 positive.”

“In this phase 3 IMpassion130 study, PD-L1 expression on immune cells is a predictive biomarker for selecting patients who benefit clinically during first-line treatment with atezolizumab + nab-paclitaxel for metastatic triple-negative breast cancer,” she concluded, adding that “patients with newly diagnosed metastatic and unresectable locally advanced triple-negative breast cancer should be routinely tested for their PD-L1 immune cell status to determine if they might benefit from the combination of atezolizumab + nab-paclitaxel.

IMpassion130 was sponsored by Hoffman-La Roche. Dr. Emens reported receiving royalties and consulting fees from several companies. She has contracts with Roche/Genentech, Corvus, AstraZeneca, and EMD Serono, and ownership in Molecuvax. She receives other support from DSMB and Syndax, and has received grants from Aduro Biotech, Merck, Maxcyte, and the Breast Cancer Research Foundation. She also reported serving as a member of the Food and Drug Administration Advisory Committee on Tissue, Cell, and Gene Therapies, and is a member of the board of directors for the Society of Immunotherapy for Cancer.

SOURCE: Emens L et al. SABCS 2018, Abstract GS1-04.

SAN ANTONIO – Programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells is the best predictor of response to atezolizumab + nab-paclitaxel in patients with untreated metastatic triple-negative breast cancer, according to exploratory efficacy analyses of data from the phase 3 IMpassion130 trial.

The analyses of data for the 902 patients randomized to receive the PD-L1 inhibitor atezolizumab (Tecentriq) plus nanoparticle albumin-bound (nab)–paclitaxel or placebo plus nab-palcitaxel for the study also showed consistency between local and central estrogen-receptor, progesterone-receptor, and human epidermal growth factor–receptor 2 testing, Leisha A. Emens, MD, reported at the San Antonio Breast Cancer Symposium.

“IMpassion130 is the first phase 3 study to demonstrate a benefit from [atezolizumab + nab-paclitaxel] in metastatic triple-negative breast cancer (mTNBC),” said Dr. Emens, professor of medicine in hematology/oncology, coleader of the Hillman Cancer Immunology and Immunotherapy Program, and director of translational immunotherapy for the Women’s Cancer Research Center at the University of Pittsburgh Medical Center.

She explained that progression-free survival (PFS) was significantly better in PD-L1–positive mTNBC patients treated with the atezolizumab + nab-paclitaxel, than in those who received placebo + nab-paclitaxel (hazard ratios in the intent-to-treat population, 0.8 and 0.62, respectively).

At the first interim overall survival analysis, a clinically meaningful improvement in OS was seen in PD-L1–positive patients in the treatment group (HR, 0.62; median OS improvement from 15.5 months with placebo to 25 months), she added.

In exploratory analyses, Dr. Emens and her colleagues sought to evaluate whether preexisting immune biology is associated with clinical benefit from atezolizumab + nab-paclitaxel, as has been demonstrated in studies of other agents that target the PD-1 pathway in other cancer types of cancer. They also assessed BRCA 1/2 mutation status as a biomarker for response.

“In patients enrolled on the IMpassion130 trial we found that PD-L1 in triple-negative breast cancer was expressed primarily on tumor-infiltrating immune cells,” she said. “In contrast to this, we found a very low rate of PD-L1 expression specifically on tumor cells across the patient population.”

Looking at both of those biomarkers together showed that a majority of patients with expression of PD-L1 on tumor cells were included in the PD-L1 immune cell–positive population, with only 2% having PD-L1 expression exclusively on their tumor cells.

Data previously reported at the European Society for Medical Oncology and published in the New England Journal of Medicine showed a PFS benefit, as well as a clinically meaningful improvement in OS of nearly 10 months, specifically in patients with PD-L1 immune cell–positive lesions treated with atezolizumab + nab-paclitaxel, she noted.

“In data presented for the first time today you can see that PD-L1–negative patients derive no overall survival benefit as there was no treatment effect with this therapy combination,” she said.

A trend was seen toward an association between immune cell positivity and poor prognosis, but this was not statistically significant, she said.

“Taken together, these data definitively show that PD-L1 immune cell positivity is predictive of both progression-free and overall survival benefit with atezolizumab + nab-paclitaxel,” she said.

She and her colleagues also looked at the level of PD-L1 expression in immune cells to assess whether there is a threshold that might be required.

“As long as there was a PD-L1 expression level of 1% or more in the immune cells, there was a significant progression-free and overall survival benefit for patients treated with atezolizumab + nab-paclitaxel. This suggests that this expression of over 1% will represent a threshold for identifying those patients who are likely to benefit from this combination,” she said.

Further assessment by CD8 T-cell status showed that patients who had CD8-positive T cells but who were PD-L1 immune cell negative had no benefit from atezolizumab + nab-paclitaxel, whereas those who were positive for both CD8 and PD-L1 expression on their immune cells derived significant PFS and OS benefit (HR, 0.89 and 0.77, respectively).

“So patients with CD8-positive tumors derive clinical benefit only if their tumors are also PD-L1-positive,” she said.

Similarly, no clinical benefit was seen in patients with stromal tumor-infiltrating lymphocyte (TIL)–positive tumors but who were PD-L1-negative, whereas those with stromal TIL-positive PD-L1–positive tumors derived significant PFS and OS benefit (HRs, 0.99 and 1.53, respectively), and this was also seen in the 15% of evaluable patients who had BRCA mutations.

“In patients who were BRCA mutated, but who were PD-L1 immune cell negative, there was no association of progression-free survival or an overall survival benefit [with atezolizumab + nab-paclitaxel]. In contrast, in patients who were BRCA mutated but PD-L1 immune cell positive ... there was an association with progression-free survival and a trend toward overall survival,” she said, noting that while the BRCA mutation findings are limited by small numbers, “they do show that mutations in BRCA and PD-L1 expression in immune cells are independent biomarkers; patients with BRCA1 or 2 mutations derive clinical benefit only if their tumors are also PD-L1 positive.”

“In this phase 3 IMpassion130 study, PD-L1 expression on immune cells is a predictive biomarker for selecting patients who benefit clinically during first-line treatment with atezolizumab + nab-paclitaxel for metastatic triple-negative breast cancer,” she concluded, adding that “patients with newly diagnosed metastatic and unresectable locally advanced triple-negative breast cancer should be routinely tested for their PD-L1 immune cell status to determine if they might benefit from the combination of atezolizumab + nab-paclitaxel.

IMpassion130 was sponsored by Hoffman-La Roche. Dr. Emens reported receiving royalties and consulting fees from several companies. She has contracts with Roche/Genentech, Corvus, AstraZeneca, and EMD Serono, and ownership in Molecuvax. She receives other support from DSMB and Syndax, and has received grants from Aduro Biotech, Merck, Maxcyte, and the Breast Cancer Research Foundation. She also reported serving as a member of the Food and Drug Administration Advisory Committee on Tissue, Cell, and Gene Therapies, and is a member of the board of directors for the Society of Immunotherapy for Cancer.

SOURCE: Emens L et al. SABCS 2018, Abstract GS1-04.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – After a 2-year follow-up, the efficacy and cardiac toxicity profile between CT-P6, a trastuzumab biosimilar candidate, and trastuzumab as neoadjuvant and then adjuvant therapy for patients with early HER2-positive breast cancer remains consistent with previous results.

Similarity in safety and efficacy at 1 year was previously demonstrated in the phase 3 trial, as well as similarity in cardiac toxicity at a median of 19 months. Updated disease-free survival, overall survival, and cardiac toxicity with a median follow-up of 2 years will be presented by Francisco J. Esteva, MD, PhD, of the Laura & Isaac Perlmutter Cancer Center at NYU Langone Health, New York, in a poster presentation at the San Antonio Breast Cancer Symposium.

For the trial, 549 patients with HER2-positive early breast cancer were randomized to receive CT-P6 (n = 271) or trastuzumab (n = 278) in combination with docetaxel (cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (cycles 5-8). CT-P6 or trastuzumab was administered at 8 mg/kg (cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received CT-P6 or trastuzumab monotherapy and then entered the follow-up period.

A total of 528 patients entered the follow-up period, with a median duration of 27 months. Disease-free and overall survival were similar in the two arms in both the per-protocol set and the intention-to-treat set. In the intention-to-treat set, the 2-year disease-free survival was 86% (95% confidence interval, 80%-90%) in the CT-P6 arm and 90% (95% CI, 85%-93%) in the trastuzumab arm. Two-year overall survival was 97% (95% CI, 93%-98%) in the CT-P6 arm and 98% (95% CI, 96%-99%) in the trastuzumab arm. Median disease-free and overall survival have not been reached, according to the abstract.

No new cases of heart failure were reported during the follow-up period. Left ventricular ejection fraction was similar in both arms. The efficacy and cardiac toxicity profile between CT-P6 and trastuzumab were consistent with published data.

“CT-P6 was consistently well tolerated with a similar cardiotoxicity profile to that of trastuzumab through a long duration of follow-up,” Dr. Esteva and authors said.

The study sponsor is Celltrion, maker of CT-P6. Dr. Esteva disclosed a consulting or advisory role with Celltrion, as well as relationships with various other pharmaceutical companies.

SOURCE: Esteva FJ et al. SABCS 2018, Abstract P6-17-03.

SAN ANTONIO – After a 2-year follow-up, the efficacy and cardiac toxicity profile between CT-P6, a trastuzumab biosimilar candidate, and trastuzumab as neoadjuvant and then adjuvant therapy for patients with early HER2-positive breast cancer remains consistent with previous results.

Similarity in safety and efficacy at 1 year was previously demonstrated in the phase 3 trial, as well as similarity in cardiac toxicity at a median of 19 months. Updated disease-free survival, overall survival, and cardiac toxicity with a median follow-up of 2 years will be presented by Francisco J. Esteva, MD, PhD, of the Laura & Isaac Perlmutter Cancer Center at NYU Langone Health, New York, in a poster presentation at the San Antonio Breast Cancer Symposium.

For the trial, 549 patients with HER2-positive early breast cancer were randomized to receive CT-P6 (n = 271) or trastuzumab (n = 278) in combination with docetaxel (cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (cycles 5-8). CT-P6 or trastuzumab was administered at 8 mg/kg (cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received CT-P6 or trastuzumab monotherapy and then entered the follow-up period.

A total of 528 patients entered the follow-up period, with a median duration of 27 months. Disease-free and overall survival were similar in the two arms in both the per-protocol set and the intention-to-treat set. In the intention-to-treat set, the 2-year disease-free survival was 86% (95% confidence interval, 80%-90%) in the CT-P6 arm and 90% (95% CI, 85%-93%) in the trastuzumab arm. Two-year overall survival was 97% (95% CI, 93%-98%) in the CT-P6 arm and 98% (95% CI, 96%-99%) in the trastuzumab arm. Median disease-free and overall survival have not been reached, according to the abstract.

No new cases of heart failure were reported during the follow-up period. Left ventricular ejection fraction was similar in both arms. The efficacy and cardiac toxicity profile between CT-P6 and trastuzumab were consistent with published data.

“CT-P6 was consistently well tolerated with a similar cardiotoxicity profile to that of trastuzumab through a long duration of follow-up,” Dr. Esteva and authors said.

The study sponsor is Celltrion, maker of CT-P6. Dr. Esteva disclosed a consulting or advisory role with Celltrion, as well as relationships with various other pharmaceutical companies.

SOURCE: Esteva FJ et al. SABCS 2018, Abstract P6-17-03.

SAN ANTONIO – After a 2-year follow-up, the efficacy and cardiac toxicity profile between CT-P6, a trastuzumab biosimilar candidate, and trastuzumab as neoadjuvant and then adjuvant therapy for patients with early HER2-positive breast cancer remains consistent with previous results.

Similarity in safety and efficacy at 1 year was previously demonstrated in the phase 3 trial, as well as similarity in cardiac toxicity at a median of 19 months. Updated disease-free survival, overall survival, and cardiac toxicity with a median follow-up of 2 years will be presented by Francisco J. Esteva, MD, PhD, of the Laura & Isaac Perlmutter Cancer Center at NYU Langone Health, New York, in a poster presentation at the San Antonio Breast Cancer Symposium.

For the trial, 549 patients with HER2-positive early breast cancer were randomized to receive CT-P6 (n = 271) or trastuzumab (n = 278) in combination with docetaxel (cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (cycles 5-8). CT-P6 or trastuzumab was administered at 8 mg/kg (cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received CT-P6 or trastuzumab monotherapy and then entered the follow-up period.

A total of 528 patients entered the follow-up period, with a median duration of 27 months. Disease-free and overall survival were similar in the two arms in both the per-protocol set and the intention-to-treat set. In the intention-to-treat set, the 2-year disease-free survival was 86% (95% confidence interval, 80%-90%) in the CT-P6 arm and 90% (95% CI, 85%-93%) in the trastuzumab arm. Two-year overall survival was 97% (95% CI, 93%-98%) in the CT-P6 arm and 98% (95% CI, 96%-99%) in the trastuzumab arm. Median disease-free and overall survival have not been reached, according to the abstract.

No new cases of heart failure were reported during the follow-up period. Left ventricular ejection fraction was similar in both arms. The efficacy and cardiac toxicity profile between CT-P6 and trastuzumab were consistent with published data.

“CT-P6 was consistently well tolerated with a similar cardiotoxicity profile to that of trastuzumab through a long duration of follow-up,” Dr. Esteva and authors said.

The study sponsor is Celltrion, maker of CT-P6. Dr. Esteva disclosed a consulting or advisory role with Celltrion, as well as relationships with various other pharmaceutical companies.

SOURCE: Esteva FJ et al. SABCS 2018, Abstract P6-17-03.