Unexpectedly Huge Survival Benefit With Pertuzumab and Trastuzumab in HER2-Positive Metastatic Breast Cancer

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Javier Cortés, MD

To the best of my knowledge, these are the best overall survival data in the history of metastatic breast cancer trials.

—Javier Cortés, MD

In my opinion, the combination of pertuzumab (Perjeta) and trastuzumab (Herceptin) is one of the most important advances in the field of metastatic breast cancer in the past 10 years. As recently reported by Swain, my other colleagues, and me and reviewed in this issue of The ASCO Post, the CLEOPATRA trial, designed to demonstrate the benefit of pertuzu­mab, trastuzumab, and chemo-based therapy over trastuzumab and chemo-based therapy in terms of progression-free survival, also showed an improvement in overall survival.1

However, what was absolutely unexpected was the huge survival benefit observed. Usually, an improvement in progression-free survival does not translate into a statistically significant difference in overall survival. Many reasons might explain that, including the prolonged post-progression survival observed in patients with metastatic breast cancer. However, in this case, even with a very prolonged post-progression survival, improvement in overall survival was not only statistically significant, but it represents an impressive absolute improvement.

To the best of my knowledge, these are the best overall survival data in the history of metastatic breast cancer trials. Median overall survival was 56.5 months (95% confidence interval [CI] = 49.3 months to not reached) in the pertuzumab group vs 40.8 months (95% CI = 35.8–48.3 months) in the control group (difference = 15.7 months, hazard ratio [HR] = 0.68, P < .001). The improvement in median progression-free survival was amazing as well but shorter (18.7 vs 12.4 months, HR = 0.68, P < .001).

How is this possible? How is it possible to achieve an improvement in median progression-free survival that is much shorter than the improvement in median overall survival? This is clearly something that investigators should be studying. However, in the meantime, pertuzumab, trastuzumab, and taxanes should be considered the new standard of care for first-line treatment in patients with HER2-positive metastatic breast cancer. ■

Disclosure: Dr. Cortés is a consultant for Roche/Genentech and Celgene; has received honoraria from Roche/Genentech, Novartis, Eisai, and Celgene; and has stock in MedSIR.


1. Swain SM, Baselga J, Kim SB, et al: Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372:724-734, 2015.


Dr. Cortés is Head of the Breast Cancer Program at Vall d’Hebron Institute of Oncology and Medical Oncologist, Medica Scientia Innovation Research (MedSIR), in Barcelona, Spain.


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