Sunil Verma, MD
Sunil Verma, MD, Professor and Head of the Department of Oncology and Medical Director of the Tom Baker Cancer Centre of the University of Calgary in Canada, was the study’s formal discussant. He cited several limitations of the study: It was an open-label study, was initially a phase II study but expanded to phase III (implementing hierarchical testing), was underpowered to detect an overall survival benefit, and used capecitabine/trastuzumab (Herceptin) as the control arm rather than ado-trastuzumab emtansine (Kadcyla), which is now considered the standard of care in the second-line setting.
“Given that the primary endpoint is not significant, more mature overall survival data are not going to be that helpful,” he suggested.
Dr. Verma compared the outcomes to those of the first-line CLEOPATRA trial,1 noting that the hazard ratios for overall survival were almost the same—0.68 in PHEREXA and 0.66 in CLEOPATRA—but they were different for progression-free survival—0.82 and 0.69, respectively.
“When you have a study clearly showing a benefit for pertuzumab [Perjeta] in the first-line setting, I don’t see a rationale for considering this agent in the second-line setting,” he said, “especially with efficacy shown for [ado-trastuzumab emtansine] in the second-line and a progression-free survival and overall survival benefit that is significant. The algorithm for using taxane/trastuzumab/pertuzumab in the first-line setting and [ado-trastuzumab emtansine] in the second line should stay consistent.”
Jonas Bergh, MD
During the discussion of the study, Jonas Bergh, MD, Head of the Breast Cancer Section of the Karolinska Institute in Stockholm, offered a somewhat different perspective. “The hazard ratios are indicative of a positive signal…. Though clearly not statistically significant, the 8-month difference in overall survival suggests there may be something there,” he suggested. “While P values are of course related to follow-up time and event rates, I wonder if the interpretation should be slightly more dynamic than [is seen by] staring at these P values.” ■
Disclosure: Dr. Verma has received honoraria from Pfizer, Novartis, Roche/Genentech, Amgen, AstraZeneca, and Boehringer Ingelheim and research funding from Sanofi-Aventis; has had a consulting or advisory role with Roche/Genentech, Amgen, Novartis, AstraZeneca, Eli Lilly, and Eisai; and has served on the speakers bureau for Novartis. Dr. Bergh has received research funding (institutional) from Amgen, AstraZeneca, Bayer HealthCare Pharmaceuticals, Merck, Pfizer, Roche, and Sanofi.
We observed an 8-month increase in median overall survival with pertuzumab, to 36.1 months. Statistical significance for overall survival cannot be claimed due to the hierarchical testing. However, the magnitude of benefit is in keeping with prior experience of pertuzumab in...!-->!-->