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VIENNA – One year of adjuvant trastuzumab after primary therapy for HER2-positive early breast cancer remains the recommended standard of care, according to the first report of a landmark analysis from the HERA trial and findings from the PHARE study.
The latest data to emerge from the HERA (Herceptin Adjuvant) trial show similar disease-free survival and overall survival for 1 and 2 years of adjuvant trastuzumab (Herceptin), with respective hazard ratios (HRs) of 0.99 (95% confidence interval, 0.85-1.14; P =.86) and 1.05 (95% CI, 0.86-1.28; P = .63).
In the PHARE (Protocol of Herceptin Adjuvant With Reduced Exposure) study, which was designed as a noninferiority trial, disease-free survival at 1, 2, 3, and 4 years was not statistically different for those given 6 months versus 1 year of adjuvant trastuzumab. The respective disease-free survivals at 4 years were 84.9% and 87.8%, with an HR of 1.28 (95% CI 1.05-1.56, P = .29).
"In my opinion, 1 year adjuvant trastuzumab is still considered the standard of care," ASCO president Dr. Barbara Swain commented.
Dr. Swain, who is the director of the Washington Cancer Institute, was the invited discussant for the trials after their presentation, Oct. 1, at the European Society for Medical Oncology Congress.
"It’s very important that the presented data be peer reviewed and certainly longer follow-up for PHARE be obtained before final conclusions can be made," she added.
HERA Now at 8-Years’ Follow-up
To date, HERA has been the only trial to look at whether prolonging trastuzumab for more than 1 year may further increase patient survival. The trial findings, which were originally published in 2005 (N. Engl. J. Med. 2005;353:1659-72), showed that 1 year of treatment after adjuvant chemotherapy significantly improved disease-free survival among women with HER2-positive breast cancer.
Now with a median of 8 years of follow-up, the HERA investigators were able to report on the 2-year versus 1-year comparison, using a landmark analysis that considered 3,105 women who had remained disease free for at least 1 year since being randomized to trastuzumab.
Disease-free survivals for 2 years versus 1 year of trastuzumab were comparable, at 89.1% and 86.7%, respectively, at 1 year; 81.6% and 81.0% at 5 years; and 75.8% and 76.0% at 8 years.
Disease-free survivals according to hormone receptor status were also comparable, although an intriguing finding was that there was a slight difference in disease-free survival favoring 2 years of trastuzumab in HR-negative women at about the 3-year mark.
"This raises hypotheses and illustrates the need to evaluate results by receptor status," Richard Gelber, Ph.D., one of the biostatisticians for the HERA trial, commented at a press briefing.
Looking at safety, secondary cardiac end points and other adverse events were increased in the 2-year trastuzumab arm, with 7.2% of patients having a decreased left ventricular ejection fraction versus 4.1% of those treated for 1 year, and 0.9% of those who were in the observation arm.
"Today, I am happy to report that the overall survival advantage for trastuzumab versus observation is sustained, it’s robust, and it’s long term," said Dr. Gelber, of the Dana-Farber Cancer Institute in Boston.
Rationale for Shorter Treatment
The rationale for investigating the possible benefit of shorter trastuzumab treatment is twofold, explained Dr. Xavier Pivot, of the Université de Franche-Comté in Besançon, who presented the PHARE data. First, the FinHer study suggested that just 9 weeks of trastuzumab could perhaps provide a similar magnitude of benefit as 1 year of therapy (N. Engl. J. Med. 2006;354:809-20). Second, there were cardiotoxicity concerns with trastuzumab, which might be reduced by a shorter duration of treatment.
The PHARE trial was initiated in 2006 and involved 3,380 women who were treated for 6 or 12 months with trastuzumab.
"Results were inconclusive for the noninferiority between 6 months’ duration and 12 months’ duration," Dr. Pivot said.
"Nevertheless, there was a trend favoring the standard 12 months’ treatment." The hazard ratio for overall survival after a median of 3.6 years was 1.47 (95% CI, 1.07-2.02).
A significant difference in cardiac events favored the shorter treatment regimen, however, and a multivariate analysis is due to be presented at the San Antonio Breast Cancer Symposium in December.
Practice Remains Unchanged
"These are extremely important, well-designed, phase III trials on the duration of trastuzumab treatment in the adjuvant setting," Dr. Swain said.
Commenting on the PHARE study results, she said: "The observed hazard ratio was 1.28, so it is inconclusive statistically in terms of noninferiority." The bar for noninferiority was set at an HR of 1.15.
"However, since the lower confidence interval is greater than 1, we can conclude that 12 months at this time with a short follow-up is better than 6 months," Dr. Swain said.
The use of concurrent versus sequential chemotherapy could have influenced the results, she suggested. The HR for concurrent chemotherapy with docetaxel and trastuzumab, which was received by 42% of patients, was 1.17 (95% CI, 0.89-1.54). The HR for sequential chemotherapy was 1.39 (95% CI, 1.05-1.85).
If the study had continued, she added, the HR for 6 months versus 1 year of treatment may have shown that the shorter duration is at least as good as the standard regimen.
There are several ongoing studies still looking at the optimum duration of adjuvant trastuzumab in the early breast cancer setting, Dr. Swain observed, These include the Persephone, Hellenic, Short-Her, and SOLD trials.
Persephone and Hellenic are looking at 6 versus 12 months of trastuzumab, but the former is still accruing patients until the end of next year and won’t report until the middle of 2016 at the earliest.
Results of the Short-Her and SOLD trials, which are looking at 9 weeks versus 12 months of trastuzumab, should appear sooner. Until results are available, there is no practice-changing message, and 1 year of trastuzumab – at least outside the clinical trial setting – should remain the current practice standard.
The HERA trial was run by the Breast International Group with funding from Roche. Dr. Gelber disclosed he had no conflicts of interest. The PHARE trial was funded and conducted by the French National Cancer Institute. Dr. Pivot has received honoraria from and acted as a consultant to Roche and GlaxoSmithKline. Dr. Swain disclosed receiving honoraria from Genentech/Roche.
VIENNA – One year of adjuvant trastuzumab after primary therapy for HER2-positive early breast cancer remains the recommended standard of care, according to the first report of a landmark analysis from the HERA trial and findings from the PHARE study.
The latest data to emerge from the HERA (Herceptin Adjuvant) trial show similar disease-free survival and overall survival for 1 and 2 years of adjuvant trastuzumab (Herceptin), with respective hazard ratios (HRs) of 0.99 (95% confidence interval, 0.85-1.14; P =.86) and 1.05 (95% CI, 0.86-1.28; P = .63).
In the PHARE (Protocol of Herceptin Adjuvant With Reduced Exposure) study, which was designed as a noninferiority trial, disease-free survival at 1, 2, 3, and 4 years was not statistically different for those given 6 months versus 1 year of adjuvant trastuzumab. The respective disease-free survivals at 4 years were 84.9% and 87.8%, with an HR of 1.28 (95% CI 1.05-1.56, P = .29).
"In my opinion, 1 year adjuvant trastuzumab is still considered the standard of care," ASCO president Dr. Barbara Swain commented.
Dr. Swain, who is the director of the Washington Cancer Institute, was the invited discussant for the trials after their presentation, Oct. 1, at the European Society for Medical Oncology Congress.
"It’s very important that the presented data be peer reviewed and certainly longer follow-up for PHARE be obtained before final conclusions can be made," she added.
HERA Now at 8-Years’ Follow-up
To date, HERA has been the only trial to look at whether prolonging trastuzumab for more than 1 year may further increase patient survival. The trial findings, which were originally published in 2005 (N. Engl. J. Med. 2005;353:1659-72), showed that 1 year of treatment after adjuvant chemotherapy significantly improved disease-free survival among women with HER2-positive breast cancer.
Now with a median of 8 years of follow-up, the HERA investigators were able to report on the 2-year versus 1-year comparison, using a landmark analysis that considered 3,105 women who had remained disease free for at least 1 year since being randomized to trastuzumab.
Disease-free survivals for 2 years versus 1 year of trastuzumab were comparable, at 89.1% and 86.7%, respectively, at 1 year; 81.6% and 81.0% at 5 years; and 75.8% and 76.0% at 8 years.
Disease-free survivals according to hormone receptor status were also comparable, although an intriguing finding was that there was a slight difference in disease-free survival favoring 2 years of trastuzumab in HR-negative women at about the 3-year mark.
"This raises hypotheses and illustrates the need to evaluate results by receptor status," Richard Gelber, Ph.D., one of the biostatisticians for the HERA trial, commented at a press briefing.
Looking at safety, secondary cardiac end points and other adverse events were increased in the 2-year trastuzumab arm, with 7.2% of patients having a decreased left ventricular ejection fraction versus 4.1% of those treated for 1 year, and 0.9% of those who were in the observation arm.
"Today, I am happy to report that the overall survival advantage for trastuzumab versus observation is sustained, it’s robust, and it’s long term," said Dr. Gelber, of the Dana-Farber Cancer Institute in Boston.
Rationale for Shorter Treatment
The rationale for investigating the possible benefit of shorter trastuzumab treatment is twofold, explained Dr. Xavier Pivot, of the Université de Franche-Comté in Besançon, who presented the PHARE data. First, the FinHer study suggested that just 9 weeks of trastuzumab could perhaps provide a similar magnitude of benefit as 1 year of therapy (N. Engl. J. Med. 2006;354:809-20). Second, there were cardiotoxicity concerns with trastuzumab, which might be reduced by a shorter duration of treatment.
The PHARE trial was initiated in 2006 and involved 3,380 women who were treated for 6 or 12 months with trastuzumab.
"Results were inconclusive for the noninferiority between 6 months’ duration and 12 months’ duration," Dr. Pivot said.
"Nevertheless, there was a trend favoring the standard 12 months’ treatment." The hazard ratio for overall survival after a median of 3.6 years was 1.47 (95% CI, 1.07-2.02).
A significant difference in cardiac events favored the shorter treatment regimen, however, and a multivariate analysis is due to be presented at the San Antonio Breast Cancer Symposium in December.
Practice Remains Unchanged
"These are extremely important, well-designed, phase III trials on the duration of trastuzumab treatment in the adjuvant setting," Dr. Swain said.
Commenting on the PHARE study results, she said: "The observed hazard ratio was 1.28, so it is inconclusive statistically in terms of noninferiority." The bar for noninferiority was set at an HR of 1.15.
"However, since the lower confidence interval is greater than 1, we can conclude that 12 months at this time with a short follow-up is better than 6 months," Dr. Swain said.
The use of concurrent versus sequential chemotherapy could have influenced the results, she suggested. The HR for concurrent chemotherapy with docetaxel and trastuzumab, which was received by 42% of patients, was 1.17 (95% CI, 0.89-1.54). The HR for sequential chemotherapy was 1.39 (95% CI, 1.05-1.85).
If the study had continued, she added, the HR for 6 months versus 1 year of treatment may have shown that the shorter duration is at least as good as the standard regimen.
There are several ongoing studies still looking at the optimum duration of adjuvant trastuzumab in the early breast cancer setting, Dr. Swain observed, These include the Persephone, Hellenic, Short-Her, and SOLD trials.
Persephone and Hellenic are looking at 6 versus 12 months of trastuzumab, but the former is still accruing patients until the end of next year and won’t report until the middle of 2016 at the earliest.
Results of the Short-Her and SOLD trials, which are looking at 9 weeks versus 12 months of trastuzumab, should appear sooner. Until results are available, there is no practice-changing message, and 1 year of trastuzumab – at least outside the clinical trial setting – should remain the current practice standard.
The HERA trial was run by the Breast International Group with funding from Roche. Dr. Gelber disclosed he had no conflicts of interest. The PHARE trial was funded and conducted by the French National Cancer Institute. Dr. Pivot has received honoraria from and acted as a consultant to Roche and GlaxoSmithKline. Dr. Swain disclosed receiving honoraria from Genentech/Roche.
VIENNA – One year of adjuvant trastuzumab after primary therapy for HER2-positive early breast cancer remains the recommended standard of care, according to the first report of a landmark analysis from the HERA trial and findings from the PHARE study.
The latest data to emerge from the HERA (Herceptin Adjuvant) trial show similar disease-free survival and overall survival for 1 and 2 years of adjuvant trastuzumab (Herceptin), with respective hazard ratios (HRs) of 0.99 (95% confidence interval, 0.85-1.14; P =.86) and 1.05 (95% CI, 0.86-1.28; P = .63).
In the PHARE (Protocol of Herceptin Adjuvant With Reduced Exposure) study, which was designed as a noninferiority trial, disease-free survival at 1, 2, 3, and 4 years was not statistically different for those given 6 months versus 1 year of adjuvant trastuzumab. The respective disease-free survivals at 4 years were 84.9% and 87.8%, with an HR of 1.28 (95% CI 1.05-1.56, P = .29).
"In my opinion, 1 year adjuvant trastuzumab is still considered the standard of care," ASCO president Dr. Barbara Swain commented.
Dr. Swain, who is the director of the Washington Cancer Institute, was the invited discussant for the trials after their presentation, Oct. 1, at the European Society for Medical Oncology Congress.
"It’s very important that the presented data be peer reviewed and certainly longer follow-up for PHARE be obtained before final conclusions can be made," she added.
HERA Now at 8-Years’ Follow-up
To date, HERA has been the only trial to look at whether prolonging trastuzumab for more than 1 year may further increase patient survival. The trial findings, which were originally published in 2005 (N. Engl. J. Med. 2005;353:1659-72), showed that 1 year of treatment after adjuvant chemotherapy significantly improved disease-free survival among women with HER2-positive breast cancer.
Now with a median of 8 years of follow-up, the HERA investigators were able to report on the 2-year versus 1-year comparison, using a landmark analysis that considered 3,105 women who had remained disease free for at least 1 year since being randomized to trastuzumab.
Disease-free survivals for 2 years versus 1 year of trastuzumab were comparable, at 89.1% and 86.7%, respectively, at 1 year; 81.6% and 81.0% at 5 years; and 75.8% and 76.0% at 8 years.
Disease-free survivals according to hormone receptor status were also comparable, although an intriguing finding was that there was a slight difference in disease-free survival favoring 2 years of trastuzumab in HR-negative women at about the 3-year mark.
"This raises hypotheses and illustrates the need to evaluate results by receptor status," Richard Gelber, Ph.D., one of the biostatisticians for the HERA trial, commented at a press briefing.
Looking at safety, secondary cardiac end points and other adverse events were increased in the 2-year trastuzumab arm, with 7.2% of patients having a decreased left ventricular ejection fraction versus 4.1% of those treated for 1 year, and 0.9% of those who were in the observation arm.
"Today, I am happy to report that the overall survival advantage for trastuzumab versus observation is sustained, it’s robust, and it’s long term," said Dr. Gelber, of the Dana-Farber Cancer Institute in Boston.
Rationale for Shorter Treatment
The rationale for investigating the possible benefit of shorter trastuzumab treatment is twofold, explained Dr. Xavier Pivot, of the Université de Franche-Comté in Besançon, who presented the PHARE data. First, the FinHer study suggested that just 9 weeks of trastuzumab could perhaps provide a similar magnitude of benefit as 1 year of therapy (N. Engl. J. Med. 2006;354:809-20). Second, there were cardiotoxicity concerns with trastuzumab, which might be reduced by a shorter duration of treatment.
The PHARE trial was initiated in 2006 and involved 3,380 women who were treated for 6 or 12 months with trastuzumab.
"Results were inconclusive for the noninferiority between 6 months’ duration and 12 months’ duration," Dr. Pivot said.
"Nevertheless, there was a trend favoring the standard 12 months’ treatment." The hazard ratio for overall survival after a median of 3.6 years was 1.47 (95% CI, 1.07-2.02).
A significant difference in cardiac events favored the shorter treatment regimen, however, and a multivariate analysis is due to be presented at the San Antonio Breast Cancer Symposium in December.
Practice Remains Unchanged
"These are extremely important, well-designed, phase III trials on the duration of trastuzumab treatment in the adjuvant setting," Dr. Swain said.
Commenting on the PHARE study results, she said: "The observed hazard ratio was 1.28, so it is inconclusive statistically in terms of noninferiority." The bar for noninferiority was set at an HR of 1.15.
"However, since the lower confidence interval is greater than 1, we can conclude that 12 months at this time with a short follow-up is better than 6 months," Dr. Swain said.
The use of concurrent versus sequential chemotherapy could have influenced the results, she suggested. The HR for concurrent chemotherapy with docetaxel and trastuzumab, which was received by 42% of patients, was 1.17 (95% CI, 0.89-1.54). The HR for sequential chemotherapy was 1.39 (95% CI, 1.05-1.85).
If the study had continued, she added, the HR for 6 months versus 1 year of treatment may have shown that the shorter duration is at least as good as the standard regimen.
There are several ongoing studies still looking at the optimum duration of adjuvant trastuzumab in the early breast cancer setting, Dr. Swain observed, These include the Persephone, Hellenic, Short-Her, and SOLD trials.
Persephone and Hellenic are looking at 6 versus 12 months of trastuzumab, but the former is still accruing patients until the end of next year and won’t report until the middle of 2016 at the earliest.
Results of the Short-Her and SOLD trials, which are looking at 9 weeks versus 12 months of trastuzumab, should appear sooner. Until results are available, there is no practice-changing message, and 1 year of trastuzumab – at least outside the clinical trial setting – should remain the current practice standard.
The HERA trial was run by the Breast International Group with funding from Roche. Dr. Gelber disclosed he had no conflicts of interest. The PHARE trial was funded and conducted by the French National Cancer Institute. Dr. Pivot has received honoraria from and acted as a consultant to Roche and GlaxoSmithKline. Dr. Swain disclosed receiving honoraria from Genentech/Roche.
AT THE EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY CONGRESS
Major Findings: The hazard ratios for disease-free and overall survival comparing 1 year and 2 years of adjuvant trastuzumab in the HERA trial were 0.99 (P = .86) and 1.05 (P = .63), respectively. The respective disease-free survival rates at 4 years in the PHARE trial were 84.9% and 87.8%, with an HR of 1.28 (P = .29).
Data Sources: Findings were analyzed from the phase III HERA trial involving 5,102 women with HER2-positive breast cancer who received 1 or 2 years of adjuvant trastuzumab. The PHARE noninferiority trial included 3,380 women who were treated with 6 or 12 months of adjuvant trastuzumab.
Disclosures: The HERA trial was run by the Breast International Group with funding from Roche. Dr. Gelber disclosed he had no conflicts of interest. The PHARE trial was funded and conducted by the French National Cancer Institute. Dr. Pivot has received honoraria and acted as a consultant to Roche and GlaxoSmithKline. Dr. Swain disclosed receiving honoraria from Genentech/Roche.
