A global analysis led by Dana-Farber researchers examined detailed patient data from six clinical trials. The study compared dual immunotherapy, which combines CTLA-4 and PD-1/PD-L1 inhibitors, with single immunotherapy using only PD-1/PD-L1 inhibitors for advanced non-small cell lung cancer (NSCLC). For the overall NSCLC patient population, both immunotherapy approaches resulted in similar survival rates.
However, specific patient groups demonstrated clear benefits from dual immunotherapy. Patients with PD-L1-negative tumors (PD-L1 <1%) showed improved survival with dual immunotherapy, with 16.6% alive at 5 years compared to 9.3% with single immunotherapy. Additionally, patients whose tumors carried STK11 mutations, a group generally less responsive to standard PD-1/PD-L1 immunotherapy, experienced better outcomes with dual immunotherapy.
Conversely, for patients with PD-L1 levels of 1% or higher, or those without STK11 mutations, dual immunotherapy did not offer a notable survival advantage over single-agent PD-1/PD-L1 treatment. The study found no significant differences based on KRAS mutations or tumor histology.
These findings suggest a more personalized strategy for immunotherapy in advanced NSCLC. The results indicate that dual checkpoint blockade may be more beneficial for patients with PD-L1-negative tumors and those with STK11 mutations. Further research, including prospective randomized clinical trials, is recommended to validate these findings, refine patient selection through additional biomarkers, and improve management of side effects and treatment sequencing.