Adding Pembrolizumab to Carboplatin/Pemetrexed Seems to Improve Response in Advanced Nonsquamous NSCLC
As reported by Langer et al in The Lancet Oncology, findings in a phase II cohort of the multicohort KEYNOTE-021 study showed that the addition of first-line pembrolizumab (Keytruda) to carboplatin/pemetrexed (Alimta) significantly increased the response rate in patients with advanced nonsquamous non–small cell lung cancer (NSCLC).
Study Details
In the open-label study, 123 patients from 26 sites in the United States and Taiwan were randomized between November 2014 and January 2016 to receive 4 cycles of pembrolizumab at 200 mg plus carboplatin at an area under the curve (AUC) of 5 mg/mL/min and pemetrexed at 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy (n = 60) or 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy (n = 63).
Patients had to have chemotherapy-naive stage IIIB or IV disease without targetable EGFR (epidermal growth factor receptor) or ALK (anaplastic lymphoma kinase) genetic aberrations. The primary endpoint was the proportion of patients with an objective response as assessed by masked independent central review in the intention-to-treat population.
Response Rates
Response (all partial responses) was observed in 33 patients (55%, 95% confidence interval = 42%–68%) in the pembrolizumab-plus-chemotherapy group vs 18 patients (29%, 95% CI = 18%–41%) in the chemotherapy-alone group (P = .0016). Median time to response was 1.5 vs 2.7 months. Median duration of response was not reached in either group.
Overall, 29 of 33 responders (88%) in the pembrolizumab group and 14 of 18 responders (78%) in the chemotherapy-alone group remained alive and progression free at data cutoff. In the pembrolizumab group, response was achieved in 12 of 21 patients (57%) with PD-L1 (programmed cell death ligand 1) tumor expression > 1% and in 21 of 39 patients (54%) with PD-L1 expression ≥ 1%.
Progression-Free Survival
Median follow-up was 10.6 months. Median progression-free survival was 13.0 vs 8.9 months (hazard ratio [HR] = 0.53, P = .010). Estimated 6-month progression-free survival was 77% vs 63%. At data cutoff, 22% of patients in both groups had died (HR = 0.90, P = .39), and the estimated 6-month overall survival was 92% in both groups.
Adverse Events
Treatment-related grade ≥ 3 adverse events occurred in 39% vs 26% of patients; the most common events occurring in ≥ 5% in either group were anemia (12%) and decreased neutrophil count (5%) in the pembrolizumab group and anemia (15%) in the chemotherapy-alone group. The most common treatment-related events of any grade were fatigue (64% vs 40%), nausea (58% vs 44%), and anemia (32% vs 53%). Treatment-related death occurred in one patient in the pembrolizumab/chemotherapy group (sepsis) and in two patients in the chemotherapy-alone group (sepsis and pancytopenia).
Potential immune-related adverse events irrespective of causal attribution occurred in 22% of the pembrolizumab group vs 11% of the chemotherapy-alone group. The most common events of any grade in the pembrolizumab group were hypothyroidism (15%), hyperthyroidism (8%), and pneumonitis (5%). One case each of grade 4 infusion reaction, grade 3 skin reaction, and grade 3 pneumonitis occurred in the pembrolizumab group.
The investigators concluded: “Combination of pembrolizumab, carboplatin, and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC. This finding is being further explored in an ongoing international, randomised, double-blind, phase 3 study [KEYNOTE 189].”
The study was funded by Merck & Co.
Corey J. Langer, MD, of Abramson Cancer Center, University of Pennsylvania, is the corresponding author of The Lancet Oncology article.
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