Real-world comparative effectiveness and safety of Pertuzumab in patients with HER2+ metastatic breast cancer: A pan-Canadian population-based cohort study.

We assessed the comparative effectiveness and safety of pertuzumab plus trastuzumab and chemotherapy versus trastuzumab and chemotherapy for patients with HER2+ metastatic breast cancer (mBC) in Canada. We conducted a population-based retrospective study of patients receiving first-line treatment for mBC across eight Canadian provinces. Patients receiving trastuzumab and chemotherapy were historical comparators, and patients receiving pertuzumab plus trastuzumab and chemotherapy were the treatment group. Patients were followed until death or up to 5 years following the start of treatment (maximum follow-up to December 31, 2019). The primary outcome was overall survival (OS). One-year cumulative incidence and RDs were calculated for safety outcomes including hospitalization, emergency department visits, febrile neutropenia, and cardiac-related events. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were applied within provinces. Individual provincial survival estimates were pooled using random effects meta-analysis. 3063 patients who received first-line treatment for mBC were identified. Median OS was higher among treatment patients compared to comparator patients in most provinces. Pertuzumab was associated with a statistically significantly lower risk of mortality (pooled HRs, PSM: 0.65, 95%CI: 0.57-0.74; IPTW: 0.65, 95% CI: 0.61-0.70). The treatment group had a lower risk of hospitalization compared to the comparator group (pooled RD: -0.05, 95% CI: [-0.09]-[-0.01]). No difference in 1-year cumulative incidence of cardiac-related events was identified between groups. Pertuzumab use in practice was associated with statistically significant improved survival without apparent safety concerns among patients with mBC. Real-world evaluations allow for assessments of publicly funded treatments to inform funding policies.