AACR 2018: KEYNOTE-189: Addition of Pembrolizumab to Chemotherapy in Metastatic NSCLC
As reported at the American Association for Cancer Research (AACR) Meeting (Abstract CT075) in the The New England Journal of Medicine by Gandhi et al, the first interim analysis of the phase III KEYNOTE-189 trial has shown significant improvement in overall and progression-free survival with the addition of pembrolizumab (Keytruda) to chemotherapy in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC). The trial is ongoing.
Study Details
In the double-blind trial, 616 patients from 118 sites in 16 countries who had no sensitizing EGFR or ALK mutations and had received no previous treatment for metastatic disease were randomized 2:1 between February 2016 and March 2017 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks for up to 35 cycles plus chemotherapy. Chemotherapy consisted of 4 cycles of investigator’s choice of cisplatin 75 mg/m2 or carboplatin AUC = 5 plus pemetrexed (Alimta) 500 mg/m2 every 3 weeks followed by pemetrexed maintenance at 500 mg/m2 every 3 weeks. Randomization was stratified by programmed cell death ligand 1 (PD-L1) expression (≥ 1% vs < 1%), choice of platinum drug, and smoking history. Crossover to pembrolizumab monotherapy was permitted for placebo patients with disease progression.
The primary endpoints were overall survival and progression-free survival on blinded independent central radiologic review.
Overall and Progression-Free Survival
Median follow-up was 10.5 months. Overall survival at 12 months was 69.2% in the pembrolizumab group vs 49.4% in the placebo group (hazard ratio [HR] = 0.49, P < .001). Median overall survival was not reached in the pembrolizumab group vs 11.3 months in the placebo group. Hazard ratios favored pembrolizumab in all examined subgroups, including among patients with PD-L1 expression < 1% (n = 190; HR = 0.59, 95% confidence interval [CI] = 0.38–0.92) and ≥ 1% (n = 388; HR = 0.47, 95% CI = 0.34–0.66) and according to platinum drug used. Median progression-free survival was 8.8 months vs 4.9 months (HR = 0.52, P < .001). Progression-free survival at 12 months was 34.1% vs 17.3%. In the placebo group, 67 patients (32.5%) crossed over during the trial to receive pembrolizumab monotherapy after disease progression.
Adverse Events
Grade ≥ 3 adverse events occurred in 67.2% of the pembrolizumab group and 65.8% of the placebo group, with the most common in the pembrolizumab group being anemia (16.3% vs 15.3%) and neutropenia (15.8% vs 11.9%). Acute kidney injury was more common in the pembrolizumab group (5.2% vs 0.5%; grade ≥ 3 in 2.0%) and led to discontinuation of all study drugs in 2.0% of pembrolizumab patients. Immune-mediated adverse events occurred in 22.7% vs 11.9% of patients and were grade ≥ 3 in 8.9% vs 4.5%. Adverse events led to discontinuation of all study drugs in 13.8% vs 7.9% of patients and to pembrolizumab and placebo in 20.2% vs 10.4%. Adverse events led to death in 6.7% vs 5.9% of patients. Three immune-mediated adverse events (all cases of pneumonitis) led to death in the pembrolizumab group.
The investigators concluded, “In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.”
The study was funded by Merck.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
