Unfortunately, lung cancer remains the leading cause of mortality in Japan. Until recently, the 5-year survival rate for patients with advanced non-small-cell lung cancer (NSCLC) was less than 5%. Since the recent introduction of inhibitors of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), systemic therapy for advanced, or metastatic NSCLC underwent a significant change. This review evaluates emerging data on the efficacy and safety of immunotherapy for advanced NSCLC. PD-1 immune checkpoint inhibitor monotherapy using nivolumab or pembrolizumab showed an impressive 5-year survival rate of around 15% in previously treated patients with advanced NSCLC. Next, the immune-related adverse events can occur, but severe toxicities, such as pneumonitis or colitis, are infrequent. Immunotherapy is now the standard first-line treatment of choice, applied as either monotherapy, or combined with chemotherapy. For patients with a PD-L1 tumor proportion score (TPS) ≧50%, single-agent pembrolizumab demonstrated improved overall survival (OS) in comparison with platinum-based chemotherapy in patients with both non-squamous and squamous NSCLC without driver mutations. First-line pembrolizumab, carboplatin or cisplatin plus pemetrexed, atezolizumab, bevacizumab, carboplatin plus paclitaxel, atezolizumab, and carboplatin plus nab-paclitaxel showed significantly improved OS, compared with platinum-based chemotherapy alone in patients with advanced non-squamous NSCLC regardless of PD-L1 expression. Among these combination treatments, the use of atezolizumab, bevacizumab, and carboplatin plus paclitaxel in patients with EGFR mutations and ALK gene rearrangements is encouraging and requires further exploration. Pembrolizumab and carboplatin plus nab-paclitaxel improved OS compared with chemotherapy in patients with squamous NSCLC. To select the most appropriate candidate for immunotherapy, the identification of accurate predictive biomarkers beyond PD-L1 expression remains essential. In addition, to increase the long-term survival rate, efforts to develop strategies to overcome immunotherapy resistance should be initiated.
Kazuma Kishi (Tue,) studied this question.