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.
Sara Freeman/IMNG Medical Media
Dr. Xavier Pivot
"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.