SAN ANTONIO — One year of adjuvant trastazumab should remain the standard of care for patients with HER2-positive early-stage breast cancer, according to final results from the randomized PHARE trial presented at San Antonio Breast Cancer Symposium.
“The PHARE study was unsuccessful in demonstrating that 6 months trastazumab is noninferior to 12 months,” Xavier Pivot, MD, professor of medical oncology at Paul-Strauss Cancer Center in Strasbourg, France, said during a presentation. “This study was not the only study to assess a shorter duration of trastazumab. The PERSEPHONE study showed that 6 months trastazumab is noninferior to 12 months. The PHARE and PERSEPHONE studies are very similar in terms of trial design and results, but they provide opposite conclusions. This reflects the difficulty in defining results.”
One year of adjuvant trastuzumab (Herceptin, Genentech) has been the standard treatment for patients with HER2–positive early-stage breast cancer since 2005. However, the optimum duration of treatment has been the subject of debate.
The randomized PHARE trial included 3,380 women (median age, 54 years; range, 21-86) who underwent treatment at 156 centers in France.
Researchers assigned half of the women to the standard 12-month trastuzumab regimen. The other half received treatment for 6 months.
Noninferiority of 6 months vs. 12 months in the intention-to-treat population served as the primary endpoint. Secondary endpoints included OS and metastasis-free survival.
After median follow-up of 7.5 years, researchers reported 704 DFS events.
The adjusted HR for DFS events between the two treatment groups was 1.08 (95% CI, 0.93-1.25), which favored the 12-month regimen but was not statistically significant.
The adjusted HR for OS was 1.13 (95% CI, 0.92-1.39) and the adjusted HR for metastasis-free survival was 1.15 (95% CI, 0.96-1.37).
“The choice of the noninferiority margin will remain inherently a subject of controversy, especially in the context of oncology trials where the primary outcome is survival and the least additional death could be considered unacceptable, questioning the very feasibility of such trials,” Pivot and colleagues wrote. “Nevertheless, PHARE failed to show that 6 months of adjuvant trastuzumab was noninferior to 12 months.” – by Jennifer Southall
Pivot X, et al. Abstract GS2-07. Presented at: San Antonio Breast Cancer Symposium; Dec. 4-8, 2018; San Antonio.
Disclosures: The study was funded by the French National Cancer Institute. Please see the abstract for all authors’ relevant financial disclosures.