Research Summary
Study Title: Dual Versus Single Checkpoint Inhibition in Advanced Non-Small Cell Lung Cancer: A Pooled Patient-Level Analysis of Six Randomized Trials
Publication: The Lancet Oncology
Corresponding Dana-Farber Cancer Institute authors: Dr. Biagio Ricciuti
Summary: A global analysis led by Dana-Farber researchers combined detailed patient data from six major clinical trials to compare two types of immunotherapies for advanced non-small cell lung cancer (NSCLC): dual immunotherapy (a combination of CTLA-4 and PD-1/PD-L1 inhibitors) and single immunotherapy (PD-1/PD-L1 inhibitors alone).
For the overall NSCLC population, survival was similar with both approaches. However, two key groups clearly benefited from the more intensive dual immunotherapy. Patients whose tumors were PD-L1-negative (PD-L1 <1%) lived longer with dual immunotherapy, and at 5 years, 16.6% of these patients were still alive with dual therapy compared with 9.3% with single immunotherapy-nearly double the long-term survival rate. Patients whose tumors had STK11 mutations, a group that usually responds poorly to standard PD-1/PD-L1 immunotherapy, also had much better outcomes with dual immunotherapy. For patients whose tumors had PD-L1 levels of 1% or higher, or who did not have STK11 mutations, dual immunotherapy did not provide a clear survival advantage over single-agent PD-1/PD-L1 treatment. The study did not find meaningful differences based on KRAS mutations or tumor histology, suggesting that factors beyond KRAS status drive who benefits from dual therapy.
Significance: These findings support a more personalized approach to immunotherapy in advanced NSCLC. Rather than giving dual checkpoint blockade to all patients, the results suggest it should be focused on those most likely to benefit-specifically, patients with PD-L1-negative tumors and those with STK11 mutations, who typically have limited benefit from standard single-agent immunotherapy. More research, including prospective, randomized clinical trials, is needed to confirm these results, refine patient selection using additional biomarkers, and better understand how to manage side effects and sequence dual versus single immunotherapy over the course of treatment.
Funding: NextGenerationUE.
