In a Japanese phase II trial (Evolution) reported in The Lancet Oncology, Hata et al found that pembrolizumab plus platinum-based chemotherapy without radiotherapy was active in unresectable locally advanced non–small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50%.
Study Details
In the multicenter trial, 21 patients enrolled between May 2020 and February 2022 received induction pembrolizumab at 200 mg every 3 weeks plus four cycles of platinum-based chemotherapy (either cisplatin at 75 mg/m² or carboplatin at an area under the curve [AUC] of 5 for nonsquamous NSCLC or AUC = 6 for squamous NSCLC plus pemetrexed at 500 mg/m² for nonsquamous NSCLC or nanoparticle albumin-bound paclitaxel at 100 mg/m² on days 1, 8, and 15 for squamous NSCLC). Patients then received maintenance pembrolizumab at 200 mg with or without pemetrexed at 500 mg/m² every 3 weeks for up to 2 years. The primary endpoint was 2-year progression-free survival among all patients.
Key Findings
Patients had a median age of 73 years. Overall, 18 patients (86%) completed induction therapy and 10 patients (48%) completed maintenance therapy. Median follow-up was 32.5 months (interquartile range = 26.2–39.5 months).
A total of 14 patients (67%, 90% confidence interval [CI] = 46%–83%) were alive without disease progression at 2 years. The primary endpoint was met, since the lower limit of the 90% CI was 46%, exceeding the threshold 2-year progression-free survival rate of 20%. Median progression-free survival was not reached (95% CI = 18.7 months to not reached).
Median overall survival was 44.4 months (95% CI = 32.5 months to not reached), with a 2-year rate of 81%.
The most common grade 3 or worse adverse events were neutropenia (38%), leukopenia (19%), and pneumonia (14%). Serious adverse events occurred in 33% of patients. Grade 3 or worse immune-related adverse events occurred in 14%. No treatment-related deaths were reported.
The investigators concluded: “These findings suggest that pembrolizumab combined with platinum-based chemotherapy, without radiotherapy, might provide a feasible and promising alternative treatment strategy for patients with unresectable, locally advanced NSCLC with a PD-L1 TPS of 50% or higher.”
Akito Hata, MD, of the Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme. For full disclosures of all study authors, visit thelancet.com.
