FDA Expands Approval of Pembrolizumab Immunotherapy in Non-Small Cell Lung Cancer

For patients who are not candidates for surgery or definitive chemoradiotherapy and have stage III or metastatic (stage 4.) non-small cell lung cancer (NSCLC) , as first-line treatment, pembrolizumab (Keytruda) immunotherapy received expanded approval to include all PD-L1-positive patients, from the FDA on 11 April 2019. Patients must not have EGFR or ALK genomic aberrations, and their tumors must be PD-L1 positive (tumor proportion score, TPS ≥%1).

Pembrolizumab had previously been approved as a single agent for the first-line treatment of metastatic NSCLC in patients whose tumors had PD-L1 TPS ≥% 50.

The approval was based on a randomized, multicenter, open-label, active-controlled clinical trial involving patients with stage III or IV NSCLC who had not previously received systemic treatment for metastatic NSCLC and whose tumors were PD-L1 positive, totaling 1274 patients, called KEYNOTE-042.

Patients were randomized (assigned at random) in a 1-to-1 ratio to two arms;

• The immunotherapy arm received intravenous (into a vein) pembrolizumab every 3 weeks at a dose of 200 mg, and
• The chemotherapy arm received a carboplatin regimen containing pemetrexed or paclitaxel, at the investigator’s discretion. Randomization was stratified by ECOG performance status, histology, geographic region, and PD-L1 expression (TPS ≥% 50 versus TPS %1 to %49). Results of the KEYNOTE-042 study
•  In the study, pembrolizumab produced a statistically significant improvement in overall survival compared with chemotherapy in the patient subgroups with TPS ≥% 50, ≥% 20, and ≥% 1.
• For patients with TPS ≥% 1, median overall survival was 16.7 with pembrolizumab and 12.1 months with chemotherapy. For all PD-L1-positive patients, the use of immunotherapy reduced the risk of death by %19.
• For the TPS ≥% 20 subgroup, median overall survival was 17.7 months in the pembrolizumab arm and 13.0 months in the chemotherapy arm.
• For the TPS ≥% 50 subgroup, median overall survival was 20 months and 12.2 months for patients receiving pembrolizumab and chemotherapy, respectively.
• There was no significant difference in progression-free survival or overall response rates in any subgroup.

,In KEYNOTE-042, the most common adverse effects reported in at least %10 of patients receiving pembrolizumab as a single agent were fatigue, loss of appetite, dyspnea, cough, rash, constipation, diarrhea, nausea, hypothyroidism, pneumonia, pyrexia (fever), and weight loss.

The recommended dose of pembrolizumab for non-small cell lung cancer is every 3 weeks as a 30-minute intravenous infusion of 200 mg.