Subsequently, KEYNOTE-024 demonstrated that for advanced/metastatic NSCLC patients with PD-L1 ≥50% on TCs by the 22-C3 immunohistochemistry assay and lacking EGFR activating mutations/ ALK fusions that pembrolizumab had a significantly greater objective response rate (ORR), progression-free survival (PFS) and OS when compared to platinum-based doublets as first-line therapy ( 8, 9).īecause of KEYNOTE-024, multiple regulatory agencies and guideline panels approved pembrolizumab monotherapy for patients with newly diagnosed advanced/metastatic NSCLC, PD-L1 ≥50% on TCs and lacking EGFR activating mutations/ ALK fusions. In each of these second-line trials patients with epidermal growth factor receptor (EGFR) activating mutations did not benefit from PD-1 axis inhibitors when compared to docetaxel, with data on any included ALK rearranged patients not detailed ( 4- 7). Within KEYNOTE-010, patients with PD-L1 ≥50% on tumor cells (TCs) administered pembrolizumab had a greater magnitude of benefit compared to docetaxel than patients with PD-L1 of 1–49% ( 6). In each of these trials, there was an OS benefit when comparing the respective PD-1 or PD-L1 inhibitor to docetaxel ( 4- 7). Subsequently, randomized phase III trials comparing atezolizumab, nivolumab or pembrolizumab to docetaxel as second-line therapy were conducted in NSCLC. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-80.įollow the Oncology Center of Excellence on Twitter out recent approvals at the OCE’s podcast, Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.).Prior to the advent of inhibitory antibodies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1), the median overall survival (OS) for advanced/metastatic non-small cell lung cancer (NSCLC) patients receiving first-line platinum doublet chemotherapy was approximately 8–12 months and 5-year survival rates were estimated at 2% ( 1- 3). View full prescribing information for KEYTRUDA. The recommended pembrolizumab dose for NSCLC is 200 mg as an intravenous infusion over 30 minutes every 3 weeks. The most common adverse reactions reported in at least 10% of patients who received pembrolizumab as a single agent in KEYNOTE-042 include fatigue, decreased appetite, dyspnea, cough, rash, constipation, diarrhea, nausea, hypothyroidism, pneumonia, pyrexia, and weight loss. There were no significant differences in progression-free survival or overall response rate between arms in any population. For the TPS ≥50% subgroup, the estimated median OS was 20 months and 12.2 months for those receiving pembrolizumab and chemotherapy, respectively (HR 0.69 95% CI: 0.56, 0.85 p=0.0006). For the TPS ≥ 20% subgroup, the median OS was 17.7 months for the pembrolizumab arm and 13.0 months for the chemotherapy arm (HR 0.77 95% CI: 0.64, 0.92 p=0.004). In the TPS ≥1% population (overall population), the median OS was 16.7 and 12.1 months for the pembrolizumab and chemotherapy arms, respectively (HR 0.81 95% CI: 0.71, 0.93 p=0.0036). The trial demonstrated statistically significant OS improvements for those randomized to pembrolizumab compared with chemotherapy in all three populations. Overall survival (OS) in the TPS ≥50% NSCLC subgroup, the TPS ≥20% NSCLC subgroup, and the overall population (TPS ≥1%) were the major efficacy measures. Randomization was stratified by ECOG performance status, histology, geographic region, and PD-L1 expression (TPS ≥50% vs. Patients were randomized (1:1) to receive pembrolizumab 200 mg intravenously every 3 weeks or investigator’s choice of a carboplatin-containing regimen with either pemetrexed or paclitaxel. PD-L1 expression was determined by an immunohistochemistry assay using the PD-L1 IHC 22C3 pharmDx Kit. Pembrolizumab was previously approved as a single agent for the first-line treatment of patients with metastatic NSCLC whose tumors express PD-L1 TPS ≥50%.Īpproval was based on KEYNOTE‑042 (NCT02220894), a randomized, multicenter, open-label, active-controlled trial conducted in 1274 patients with stage III or IV NSCLC who had not received prior systemic treatment for metastatic NSCLC and whose tumors expressed PD-L1 (TPS ≥1%). Patients’ tumors must have no EGFR or ALK genomic aberrations and express PD-L1 (Tumor Proportion Score ≥1%) determined by an FDA-approved test. On April 11, 2019, the Food and Drug Administration approved pembrolizumab (KEYTRUDA, Merck Inc.) for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation or metastatic NSCLC.
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