COPENHAGEN, Denmark — The addition of pembrolizumab to standard first-line chemotherapy with carboplatin and pemetrexed significantly improved the overall response rate and prolonged PFS among patients with advanced nonsquamous non–small cell lung cancer, according to results from cohort G of the KEYNOTE-021 study presented at the European Society for Medical Oncology Congress.
“Patients with NSCLC who do not demonstrate actionable markers, either EGFR mutation or ALK or ROS1 translocations, are generally treated with first-line platinum-based combination chemotherapy,” Corey J. Langer, MD, director of the thoracic oncology program at Abramson Cancer Center of University of Pennsylvania, said during a press conference. “Pembrolizumab [Keytruda, Merck] has shown activity as a single agent in patients with advanced, pretreated NSCLC. Adding pembrolizumab to chemotherapy may improve efficacy, because the therapies have complimentary mechanisms of action and generally nonoverlapping toxicities.”
Corey J. Langer
The analysis included data from 123 patients with stage IIIB/IV, chemotherapy-naive nonsquamous NSCLC. Patients had an ECOG performance status of 0 or 1 and no EGFR mutation or ALK translocation.
Researchers stratified patients based on whether they had a tumor proportion score of 1% or greater vs. less than 1%. Patients were then randomly assigned to receive four cycles of carboplatin area under the curve 5 plus 500 mg/m2 pemetrexed every 3 weeks alone (n = 63) or with 24 months of 200 mg pembrolizumab every 3 weeks (n = 60).
Patients on the chemotherapy-alone arm were allowed to crossover to treatment with pembrolizumab if they demonstrated radiologic progression.
ORR served as the primary endpoint. Secondary endpoints included PFS, OS, safety and outcomes according to PD-L1 status.
Median follow-up was 10.6 months (range, 0.8-19.3). At that time, median exposure was 8 months in the pembrolizumab arm and 4.9 months in the chemotherapy arm. Forty-seven percent of patients remained on treatment with pembrolizumab, whereas 31% of patients were still receiving chemotherapy.
Fifty-one percent of patients (n = 32) assigned chemotherapy alone subsequently received pembrolizumab or another checkpoint inhibitor; 20 patients received pembrolizumab by crossing over to that arm, and 12 patients received treatment off study.
The ORR was 55% with pembrolizumab compared with 29% with chemotherapy alone (P = .0016). Median PFS also was significantly longer in the pembrolizumab arm (13 months vs. 8.9 months; HR = 0.53; 95% CI, 0.31-0.91).
More patients assigned pembrolizumab achieved 6-months PFS (77% vs. 63%), but an equal proportion of each arm achieved 6-month OS (92% for both).
The most common any-grade adverse events included fatigue (pembrolizumab, 64% vs. chemotherapy, 40%), nausea (58% vs. 44%) and anemia (32% vs. 53%).
Grade 3 or worse adverse events were more common in the pembrolizumab-plus-chemotherapy arm (39% vs. 26%), but this did not translate into greater rates of discontinuation due to adverse events (10% vs. 13%) or adverse event–related death (2% vs. 3%). One patient died of sepsis in the pembrolizumab arm, and one patient each died of sepsis and pancytopenia in the chemotherapy arm.
“Adding pembrolizumab to standard carboplatin–pemetrexed in nonsquamous NSCLC nearly doubles the chance of having a response to treatment, and reduced the risk for progression or death by nearly 50% over standard chemotherapy alone,” Langer said. “This combination could eventually be an effective treatment option for patients with chemotherapy-naive advanced nonsquamous NSCLC.”
A prospective randomized phase 3 trial evaluating the addition of pembrolizumab to standard chemotherapy for nonsquamous NSCLC is ongoing, Langer said. – by Alexandra Todak
Langer CJ, et al. Abstract LBA46_PR. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Disclosure: Merck funded this study. Langer reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.