Clinical Pearls & Morning Reports
Cortes et al. recently reported the findings of the final analysis of a phase 3 trial that evaluated the addition of pembrolizumab to chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer, including: those whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS; the number of PD-L1–staining cells [tumor cells, lymphocytes, and macrophages] divided by the total number of viable tumor cells, multiplied by 100) of 10 or more (CPS-10 subgroup), those whose tumors expressed PD-L1 with a CPS of 1 or more (CPS-1 subgroup), and those in the intention-to-treat population. Read the NEJM Original Article here.
Q: How effective are currently available therapies for triple-negative breast cancer?
A: Triple-negative breast cancer is an aggressive breast cancer subtype that lacks expression of estrogen and progesterone receptors and amplification or overexpression of human epidermal growth factor receptor 2 (HER2). The absence of these receptors renders endocrine and HER2-targeted therapies ineffective, leaving cytotoxic chemotherapy as the standard treatment option. However, chemotherapy results in suboptimal antitumor response rates and short overall survival and response durations. New therapeutic strategies to improve outcomes are needed.
Q: Was progression-free survival prolonged with the addition of pembrolizumb to chemotherapy in the interim analysis of the trial by Cortes et al.?
A: Data from a prespecified interim analysis of the trial by Cortes et al. showed that pembrolizumab plus chemotherapy resulted in significantly longer progression-free survival than placebo plus chemotherapy among patients with a PD-L1 combined positive score of 10 or more.
A: In the CPS-10 subgroup, 155 of 220 patients (70.5%) in the pembrolizumab–chemotherapy group and 84 of 103 patients (81.6%) in the placebo–chemotherapy group died. The median overall survival was 23.0 months (95% confidence interval [CI], 19.0 to 26.3) in the pembrolizumab–chemotherapy group and 16.1 months (95% CI, 12.6 to 18.8) in the placebo–chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.55 to 0.95; two-sided P=0.0185). In the CPS-1 subgroup, 336 of 425 patients (79.1%) in the pembrolizumab-chemotherapy group and 177 of 211 patients (83.9%) in the placebo–chemotherapy group died. The median overall survival was 17.6 months (95% CI, 15.5 to 19.5) in the pembrolizumab–chemotherapy group and 16.0 months (95% CI, 12.8 to 17.4) in the placebo–chemotherapy group (hazard ratio for death, 0.86; 95% CI, 0.72 to 1.04; two-sided P=0.1125). In the intention-to-treat population, the median overall survival was 17.2 months (95% CI, 15.3 to 19.0) in the pembrolizumab–chemotherapy group and 15.5 months (95% CI, 13.9 to 17.2) in the placebo–chemotherapy group (hazard ratio for death, 0.89; 95% CI, 0.76 to 1.05). Significance was not tested because of the prespecified multiplicity strategy.
A: As in the interim analysis, the higher incidence of immune-mediated adverse events in the pembrolizumab–chemotherapy group than in the placebo–chemotherapy group was primarily driven by hypothyroidism and hyperthyroidism. Overall, these events were generally low grade and were manageable with dose interruptions and appropriate use of supportive care.