Chemotherapy with pertuzumab and trastuzumab emtansine appeared to produce inferior survival among patients with ERBB2-positive metastatic breast cancer in routine clinical practice compared with the therapy’s performances in earlier, practice-changing drug trials, according to findings recently published in JAMA Oncology.

Researchers attribute the differences in survival to the patients’ ages and therapies they received prior to the study drugs.

“Treatment options for women with ERBB2-positive metastatic breast cancer have changed rapidly over the past two decades,” Josee-Lyne Ethier, MD, of the Department of Oncology at the Queen’s University School of Medicine, Kingston, Ontario, Canada, and colleagues wrote.

In the early 2000s, clinical trials such as the CLEOPATRA trial, which evaluated pertuzumab, trastuzumab and taxane chemotherapy, and the EMILIA trial, which examined trastuzumab emtansine, established these therapies as standard-of-care treatments for patients with ERBB2-positive metastatic breast cancer.

“...Since the initial publication of these landmark trials, they have been incorporated into clinical practice guidelines and become standard-of-care treatment options,” the researchers wrote. “It is not known how these novel and costly treatments are being deployed in routine practice and whether long-term outcomes are as expected based on results of pivotal clinical trials.”

Ethier and colleagues conducted a retrospective cohort study of patients with stage IV metastatic breast cancer who were treated with first-line pertuzumab (n = 795) or second-line trastuzumab emtansine (n = 506) between December 2013 and December 2017. The main outcome was overall survival.

The median age of patients who received pertuzumab was 57 years, while those assigned to trastuzumab emtansine were a median age of 56 years. Median OS for the whole study was 43 months (range, 16.2-unavailable). Patients received treatment for a median of 14 months (6.0-26.2)

Among patients who received trastuzumab emtansine, the number of patients who remained pertuzumab-naive fell from 74.7% (n = 68 of 91) to 18% (n = 16 of 89) between 2014 and 2017 (P < .001). Median OS with pertuzumab was 43 months, whereas median OS with trastuzumab emtansine was 15 months. This was significantly shorter than the median OS from the CLEOPATRA trial, which was 57 months in patients who received pertuzumab, and the EMILIA trial, which was 30 months in patients who received trastuzumab emtansine without pertuzumab.

“The reduced survival in the pertuzumab group may be explained by the older age of patients in routine practice; among the [trastuzumab emtansine] cohort, median survival was shorter for patients with prior receipt of pertuzumab than in the pertuzumab-naive subgroup,” the researchers wrote. “Median survival in the real-world appears inferior to results of pivotal trials, and differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice.”

Disclosures: Ethier reports personal fees from AstraZeneca, GlaxoSmithKline, Genomic Health and Merck outside the submitted work. Please see the study for all authors’ disclosures.