A NEW study from The University of Texas MD Anderson Cancer Center, Houston, Texas, has revealed that a combination of dual immunotherapy and chemotherapy improves outcomes for patients with metastatic non-squamous non-small cell lung cancer (NSCLC) who harbor specific mutations. Patients with STK11 and/or KEAP1 tumor suppressor gene mutations, known for their resistance to standard treatments, showed better responses to the addition of the immunotherapy drug tremelimumab, combined with durvalumab and chemotherapy.
The study highlights these genetic mutations as potential biomarkers to identify patients likely to benefit from this combined treatment strategy. The results showed improvement in overall response rates, with 42.9% of patients in the combination group responding to the therapy, compared to 30.2% in the immunotherapy and chemotherapy group alone, and 28% with chemotherapy alone.
STK11 and KEAP1 mutations are common in NSCLC and have been linked to poor outcomes with standard PD-1 or PD-L1 inhibitors. This research suggests that adding a CTLA-4 inhibitor such as tremelimumab could enhance the immune response and improve outcomes.
Researchers are hopeful that this approach will be adopted into clinical practice, offering new hope to patients with difficult-to-treat lung cancer. Further research should seek to compare this treatment strategy with other immunotherapy combinations, aiming to refine personalized treatment approaches.
Reference: Skoulidis et al. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature. 2024. https://doi.org/10.1038/s41586-024-07943-7.
Anaya Malik | AMJ
