Adjuvant Trastuzumab for HER2-Positive Breast Cancer: Results of Two Phase III Trials
Posted: Wednesday, August 21, 2019
Two independent trials produced conflicting results regarding the length of use of adjuvant trastuzumab for HER2-positive early breast cancer. According to Xavier Pivot, MD, of the Centre Paul Strauss, France, who conducted the PHARE trial, all colleagues, noninferiority of 6 months vs 12 months of trastuzumab treatment was not established. However, Helena M. Earl, MBBS, of the University of Cambridge, United Kingdom, found in the PERSEPHONE trial that 6-month trastuzumab is noninferior to 12-month treatment.
“Adjuvant trastuzumab standard duration should remain 12 months,” concluded Dr. Pivot’s group, whereas Dr. Earl’s work concluded that their results “support consideration of reduced-duration trastuzumab for women at similar risk as to those included in the trial.”
The PHARE trial is an open-label phase III trial that enrolled 3,384 patients across France who had confirmed nonmetastatic HER2-positive adenocarcinoma of the breast. These patients were randomly assigned to receive either 6 or 12 months of trastuzumab after completing at least 4 cycles of chemotherapy. After a median of 7.5 years, the hazard ratio for disease-free survival in the 12-month group compared with the 6-month group was 1.08. The noninferiority margin was included in 95% confidence interval, which does not establish noninferiority. During the follow-up, death occurred in 11% of patients in the 6-month group and 10.1% of patients in the 12-month group. In addition, there seemed to be no difference in side effects related to the duration of trastuzumab treatment.
In comparison, the open-label phase III PERSEPHONE trial recruited 4,089 patients from the United Kingdom with HER2-positive early breast cancer with a clear indication for chemotherapy. This trial also randomly assigned patients to receive either 6 or 12 months of trastuzumab, but it was given in combination with chemotherapy. After a median follow-up of 5.4 years, the 4-year disease-free survival was 89.4% in the 6-month group and 89.8% in the 12-month group (hazard ratio = 1.07, noninferiority P = .011). This result allowed researchers to establish noninferiority. Death occurred in 9% of patients in the 6-month group and 8% of patients in the 12-month group. Additionally, patients in the 6-month group had fewer severe adverse events than those in the 12-month group (19% vs. 24%).
Disclosure: The study authors’ disclosure information may be found at thelancet.com.