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Original Investigation
July 8, 2021

Practice Patterns and Outcomes of Novel Targeted Agents for the Treatment of ERBB2-Positive Metastatic Breast Cancer

Author Affiliations
  • 1Department of Oncology, School of Medicine, Queen’s University, Kingston, Ontario, Canada
  • 2Division of Cancer Care and Epidemiology, Cancer Research Institute, School of Medicine, Queen’s University, Kingston, Ontario, Canada
  • 3Department of Medical Oncology and Hematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada
  • 4Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
JAMA Oncol. Published online July 8, 2021. doi:10.1001/jamaoncol.2021.2140
Key Points

Question  What are the real-world survival outcomes associated with use of pertuzumab and trastuzumab emtansine (T-DM1) for ERBB2-positive metastatic breast cancer?

Findings  In this cohort study of 795 women in Ontario, Canada, median survival with pertuzumab (43 months) and T-DM1 (15 months) were substantially shorter than outcomes reported in previous pivotal trials. The reduced survival in the pertuzumab group may be explained by the older age of patients in routine practice; among the T-DM1 cohort, median survival was shorter for patients with prior receipt of pertuzumab than in the pertuzumab-naive subgroup.

Meaning  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.


Importance  Clinical trials have shown that the addition of pertuzumab to trastuzumab-based chemotherapy for first-line treatment of ERBB2-positive metastatic breast cancer is associated with considerable improvement in overall survival (OS). In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. However, there are few data describing long-term real-world outcomes with these agents.

Objective  To describe practice patterns and outcomes associated with pertuzumab and T-DM1 in routine clinical practice.

Design, Setting, and Participants  This population-based retrospective cohort study used the Ontario Cancer Registry linked to electronic treatment databases to identify all patients treated with pertuzumab and T-DM1 following reimbursement approval in Ontario, Canada, which has a single-payer public health system. Participants included women with stage IV ERBB2-positive metastatic breast cancer receiving treatment with pertuzumab for first-line metastatic indication from December 2013 through December 2017, and those treated with T-DM1 from May 2014 through December 2017. Pertuzumab and T-DM1 cohorts were analyzed separately. Data were analyzed December 2019 to December 2020.

Exposures  Treatment with pertuzumab or T-DM1.

Main Outcomes and Measures  The primary outcome was OS, determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model.

Results  The median (interquartile range [IQR]) age of the 795 women who received pertuzumab and 506 women who received T-DM1 was 57 (49-67) and 56 (48-66) years, respectively. Among the entire population, the median (IQR) OS and time on treatment was 43 (16.2-unavailable) and 14 (6.0-26.2) months, respectively. In the T-DM1 cohort, the proportion of pertuzumab-naive patients decreased over time from 68 of 91 [74.7%] in 2014 to 16 of 89 [18.0%] in 2017 (P < .001). The median (IQR) OS and time on treatment was 15 (6.7-27.7) and 4 (1.4-9.0) months, respectively. Median OS was shorter for patients with prior pertuzumab treatment than in the pertuzumab-naive subgroup (12 vs 19 months; adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = .004).

Conclusions and Relevance  In this population-based cohort study, the survival of patients treated with pertuzumab and T-DM1 in routine practice appeared inferior to results from pivotal clinical trials. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.

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