Pembrolizumab

Patients were randomly assigned in a 2:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) and chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) or placebo and chemotherapy. Randomization was stratified by the type of on-study chemotherapy (taxane or gemcitabine/carboplatin), PD-L1 expression at baseline (CPS ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Dual primary efficacy end points were PFS and OS assessed in the PD-L1 CPS of 10 or more, PD-L1 CPS of 1 or more, and ITT populations. Of the 847 patients assigned to treatment, 566 patients received pembrolizumab and chemotherapy and 281 patients received placebo and chemotherapy.[56,57]

Patients were randomly assigned in a 2:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) and chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) or placebo and chemotherapy. Randomization was stratified by the type of on-study chemotherapy (taxane or gemcitabine/carboplatin), PD-L1 expression at baseline (CPS ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Dual primary efficacy end points were PFS and OS assessed in the PD-L1 CPS of 10 or more, PD-L1 CPS of 1 or more, and ITT populations. Of the 847 patients assigned to treatment, 566 patients received pembrolizumab and chemotherapy and 281 patients received placebo and chemotherapy.[56,57]

At the second interim analysis, the median follow-up was 25.9 months in the pembrolizumab-and-chemotherapy group and 26.3 months in the placebo-and-chemotherapy group. Among patients with CPS of 10 or more, the median PFS was 9.7 months with pembrolizumab and chemotherapy and 5.6 months with placebo and chemotherapy (HRprogression or death, 0.65; 95% CI, 0.49–0.86; one-sided P = .0012 [primary objective met]). Among patients with CPS of 1 or more, the median PFS was 7.6 months with pembrolizumab and chemotherapy and 5.6 months with placebo and chemotherapy (HR, 0.74; 0.61–0.90; one-sided P = .0014 [not significant]). Among the ITT population, the median PFS was 7.5 months and 5.6 months (HR, 0.82; 0.69–0.97 [not tested]). The pembrolizumab treatment effect increased with PD-L1 enrichment.

Patients were randomly assigned in a 2:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) and chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) or placebo and chemotherapy. Randomization was stratified by the type of on-study chemotherapy (taxane or gemcitabine/carboplatin), PD-L1 expression at baseline (CPS ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Dual primary efficacy end points were PFS and OS assessed in the PD-L1 CPS of 10 or more, PD-L1 CPS of 1 or more, and ITT populations. Of the 847 patients assigned to treatment, 566 patients received pembrolizumab and chemotherapy and 281 patients received placebo and chemotherapy.[56,57]

Based on the PFS data, the FDA approved pembrolizumab and chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10).

Patients were randomly assigned in a 2:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) and chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) or placebo and chemotherapy. Randomization was stratified by the type of on-study chemotherapy (taxane or gemcitabine/carboplatin), PD-L1 expression at baseline (CPS ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Dual primary efficacy end points were PFS and OS assessed in the PD-L1 CPS of 10 or more, PD-L1 CPS of 1 or more, and ITT populations. Of the 847 patients assigned to treatment, 566 patients received pembrolizumab and chemotherapy and 281 patients received placebo and chemotherapy.[56,57]

At time of final analysis, the median follow-up was 44.1 months. In the group with a CPS of at least 10, the median OS was 23 months in the pembrolizumab-and-chemotherapy group and 16.1 months in the placebo-and-chemotherapy group (HR, 0.73; 95% CI, 0.55–0.95; two-sided P = .0185 [significant]). In the group with a CPS of at least 1, the median survival was not significantly altered (17.6 vs. 16 months; P = .1125).

Patients were randomly assigned in a 2:1 ratio to receive either pembrolizumab (200 mg every 3 weeks) and chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) or placebo and chemotherapy. Randomization was stratified by the type of on-study chemotherapy (taxane or gemcitabine/carboplatin), PD-L1 expression at baseline (CPS ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Dual primary efficacy end points were PFS and OS assessed in the PD-L1 CPS of 10 or more, PD-L1 CPS of 1 or more, and ITT populations. Of the 847 patients assigned to treatment, 566 patients received pembrolizumab and chemotherapy and 281 patients received placebo and chemotherapy.[56,57]

Grade 3 to 5 treatment-related adverse events occurred in 68.1% of patients in the pembrolizumab group and 66.9% of patients in the placebo group. Two deaths occurred in the pembrolizumab group (acute kidney injury and pneumonia). There were no deaths in the placebo group. Grade 3 to 4 immune-mediated adverse events occurred in 5.3% of patients in the pembrolizumab group, none of which led to death.