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In an interim analysis of the phase 3 trial KEYNOTE-355 the addition of pembrolizumab to chemotherapy resulted in significantly longer overall survival than chemotherapy alone
New data from KEYNOTE-355, recently published on the New England Journal of Medicine, confirm that pembrolizumab added to investigator’s choice of chemotherapy gives a significant and clinically meaningful improvement in overall survival vs chemo alone in patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer whose tumors expressed PD-L1.
The study randomized a total of 847 patients, with 566 assigned to the pembrolizumab–chemotherapy group (pembrolizumab 200 mg plus investigator’s choice of chemotherapy with nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin), and 281 to the placebo–chemotherapy group; the median follow-up was 44.1 months. In a subgroup of patients with a combined positive score (CPS, the number of PD-L1–staining tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100) of 10 or more: in this PD-L1 highly expressing tumors the median overall survival was 23.0 months in the pembrolizumab–chemotherapy group and 16.1 months in the placebo–chemotherapy group. Data were encouraging for patients in other subgroups too: in the CPS-1 subgroup, the median overall survival was 17.6 and 16.0 months in the two groups, respectively, and in the intention-to-treat population the median overall survival was 17.2 and 15.5 months, respectively. Adverse events were consistent with the known safety profiles of pembrolizumab and the chemotherapy regimens, with no new safety signals: the higher incidence of immune-mediated adverse events in the pembrolizumab–chemotherapy group was primarily driven by hypothyroidism and hyperthyroidism, but these events were generally low grade and were manageable with dose interruptions and appropriate use of supportive care.
Pembrolizumab plus chemotherapy, as authors say, resulted in significantly longer progression-free survival than chemotherapy alone among patients whose tumors expressed PD-L1 with a CPS of 10 or more: pembrolizumab plus chemotherapy provided a greater reduction in the risk of disease progression or death than chemotherapy alone, as in the CPS-10 subgroup the percentage of patients with progression-free survival at 12 months was approximately 16 percentage points higher in the pembrolizumab– chemotherapy group than in the placebo–chemotherapy group. «In this trial, first-line treatment with pembrolizumab–chemotherapy resulted in significantly longer overall survival than chemotherapy alone among patients with advanced triple-negative breast cancer whose tumors expressed PD-L1 with a CPS of 10 or more», authors conclude.