Is Pertuzumab Plus Trastuzumab Without Chemotherapy a Reasonable Treatment for ERBB2-Positive Metastatic Breast Cancer?—Reply

Abstract

To the Editor Huober and colleagues 1 conducted an important analysis of a randomized clinical trial to assess if it is reasonable for patients to receive first-line pertuzumab plus trastuzumab alone (group A) vs with chemotherapy (group B) followed by trastuzumab and emtansine after progression. The median progression-free survival was 8.4 and 23.3 months for group A and group B, respectively, suggesting that patients would have impressive statistically and clinically significant treatment benefit with chemotherapy. The authors then evaluated overall survival (OS) between 2 treatment strategies based on the 2-year survival rates, which were 79.0% (90% CI, 71.4%-85.4%) for group A and 78.1% (90% CI, 70.4%-84.5%) for group B. Note that both confidence intervals were rather large, indicating that there was not enough information to assess the relative merit between the 2 arms using this summary measure for OS.From Figure 2B, 1 the Kaplan-Meier curves for the OS are stretching out to 72 months and provide much more information about the survival profile beyond 2-year rates. In fact, the survival curve for group B is uniformly better than its counterpart for group A, especially between 24 and 72 months. With reconstructed survival data 2 from Figure 2B, the areas under the Kaplan-Meier curves up to 72 months are 50.2 and 54.2 months for group A and group B, respectively. 3,4 That is, patients in group A on average would survive 50.2 months with 72 months of follow-up. The difference (B minus A) is 4.00 months (95% CI, −2.4 to 10.3 months), which is rather asymmetric, favoring the treatment with chemotherapy. That is, the patients in the chemotherapy group might have 10.3 extra months of survival benefit but only have 2.4 months shorter survival compared with patients not receiving chemotherapy. Due to the small trial size, this treatment difference estimate for OS being not statistically significant would be expected. Based on the above totality of the progression-free survival and OS analysis results, it is not clear if we can conclude that the treatment without chemotherapy is feasible, as the authors claimed in the article. 1