Immunotherapy for non-small cell lung cancer

The initial breakthrough in the treatment of lung cancer with ICI was the launch of the PD-1 inhibitor nivolumab. In a randomized phase III trial, nivolumab showed higher objective response rate (ORR) and overall survival (OS) than docetaxel for patients with advanced squamous and non-squamous NSCLC whose disease progressed after platinum chemotherapy. Subsequently, the US FDA approved another PD-1 inhibitor, pembrolizumab, and a PD-L1 inhibitor, atezolizumab, for the same indications. These approvals were based on the superior efficacy of these drugs compared with docetaxel as a second-line treatment.

The success of ICIs in second-line treatment has opened the door for their use as first-line treatment for advanced NSCLC. In the past five years, a large number of phase III clinical trials have been conducted, and the results have shown that immune checkpoint inhibitors (ICIs) alone or in combination with platinum chemotherapy can produce durable responses and significantly improve overall survival (OS) compared with chemotherapy alone. These findings have significantly broadened the range of first-line treatment options for patients with advanced non-small cell lung cancer (NSCLC) who do not have specific EGFR mutations or ALK translocations. These options include pembrolizumab, atezolizumab, cemiplimab, nivolumab plus the CTLA-4 inhibitor ipilimumab, pembrolizumab plus platinum-based chemotherapy, atezolizumab plus platinum-based chemotherapy with or without bevacizumab (for nonsquamous histology), and nivolumab plus ipilimumab plus two cycles of platinum-based chemotherapy. The choice of treatment in the clinic depends largely on PD-L1 expression, disease severity, and tumor mutational profile.