In the phase II SPRINT trial reported in the Journal of Clinical Oncology, Ohri et al found that a chemotherapy-sparing regimen of pembrolizumab with risk-adapted radiotherapy was associated with good outcomes in patients with stage III or unresectable stage II non–small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of ≥ 50%.

Study Details

In the study, 25 patients were enrolled from three U.S. centers between August 2018 and November 2021. Patents received three cycles of induction pembrolizumab at 200 mg once every 21 days followed by a 20-fraction course of risk-adapted thoracic radiotherapy and then consolidation pembrolizumab every 3 weeks to complete a 1-year treatment course. Risk-adapted radiotherapy consisted of 55 Gy delivered to tumors or lymph nodes with a metabolic volume exceeding 20 cc and 48 Gy delivered to smaller lesions. The primary endpoint was 1-year progression-free survival; it was hypothesized the 1-year progression-free survival would be at least 65%, compared with a historical rate of approximately 40% for patients treated with standard therapy.

Progression-Free Survival

Objective response was observed in 12 patients (48%) after induction pembrolizumab. A total of 24 patients underwent definitive radiotherapy, including 3 who received radiotherapy after early discontinuation of induction pembrolizumab. Of 21 patients receiving radiotherapy after induction, all completed 20 courses, and 11 (52%) received the 48-Gy dose.

Median follow-up was 22 months. Progression-free survival rate at 1 year was 76%, exceeding the prespecified efficacy threshold (P = .003). Median progression-free survival was 26 months. Overall survival rates at 1 and 2 years were 92% and 76%, respectively; median overall survival had not been reached.

Adverse Events

Treatment-related grade 3 adverse events consisted of diarrhea/colitis in two patients (8%) and anemia, arthritis, esophagitis, pneumonitis, and weight loss in one patient (4%) each; no treatment-related grade 4 or 5 events were reported. Induction pembrolizumab was discontinued in two patients, because of treatment-related grade 3 colitis and grade 3 arthritis, respectively. No patients discontinued thoracic radiotherapy because of toxicity. Consolidation pembrolizumab was discontinued in five patients, because of pulmonary toxicity in three, rash in one, and generalized fatigue in one.

The investigators concluded: “Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with locally advanced NSCLC with a PD-L1 TPS of ≥ 50%.”

Nitin Ohri, MD, MS, of the Department of Radiation Oncology, Montefiore-Einstein Comprehensive Cancer Center, New York, is the corresponding author of the Journal of Clinical Oncology article. 

Disclosure: The study was supported by a grant from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.