A phase 1b study investigating safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with HR+/HER2- metastatic breast cancer showed antitumor activity but high rates of severe adverse events; data, recently published in NPJ Breast Cancer, do not support further investigation in these patients.
The nonrandomized, open-label, multi-cohort Phase 1b study involved 54 patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: 26 were enrolled in cohort 1 and received treatment with abemaciclib in combination with pembrolizumab and anastrozole, 28 were enrolled in cohort 2 and received treatment with abemaciclib plus pembrolizumab, in both cohorts over 21-day cycles: patients in cohort 2 received a median of three lines of prior systemic therapy in the metastatic setting. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 and 26.3 months for cohort 2, whereas data are immature for cohort 1. At the time of data cutoff, 80.8% of patients in cohort 1 and all patients in cohort 2 had discontinued treatment, mainly for progressive disease (34.6%) or adverse events (30.8%) for cohort 1 and progressive disease (67.9%) or adverse events (17.9%) for cohort 2. A total of two deaths occurred, which investigators attributed to treatment-related adverse events, both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy; there were also severe transaminase elevations, as well as neutropenia and diarrhea, as the most frequent grade ≥3 adverse events. «There were a higher rates of treatment discontinuation due to adverse events observed with abemaciclib plus pembrolizumab with/without anastrozole compared to previous reports. Overall, benefit/risk analysis based on the totality of data does not support further evaluation of this combination in the treatment of patients with HR+, HER2− metastatic breast cancer», authors conclude.
