An Effective Biomarker-Directed Combination Therapy for NSCLC

A combination of targeted therapy and immunotherapy may help patients with non-small cell lung cancer (NSCLC) overcome immune resistance and reinvigorate antitumor activity, according to a new study published in Nature Medicine. 

This study enrolled 268 patients (median age, 64 years; 58% men) with advanced NSCLC who progressed following standard-of-care therapy. The population of interest received 1 of 4 targeted therapies in combination with durvalumab: ceralasertib (ATR kinase inhibitor), olaparib (PARP inhibitor), danvatirsen (STAT3 antisense oligonucleotide), or oleclumab (anti-CD73 monoclonal antibody).

The results showed that durvalumab coupled with ceralasertib provided the greatest clinical benefit of the 4 combinations evaluated, with an objective response rate of 13.9% compared with just 2.6% with the other combinations. Moreover, the average progression-free survival was 5.8 months versus 2.7 months for other combinations, while median overall survival was 17.4 months and 9.4 months, respectively.

Based on these results, durvalumab plus ceralasertib is now being evaluated in a randomized, phase 3 trial for patients with immunotherapy-refractory NSCLC.

“Patients with advanced [NSCLC] face significant challenges when standard-of-care treatments fail,” said corresponding author John Heymach, MD, PhD, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, via a press release. “For these individuals, options become limited, emphasizing the urgent need for innovative approaches. Our study represents a promising advancement in addressing this unmet need and holds the potential to offer more effective therapeutic strategies to improve outcomes for this population.”