Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)[1]

In the last ten years, there has been a significant paradigm shift in the treatment of lung cancer. Advances in our knowledge of lung cancer biology have resulted in the creation of numerous targeted therapies and immunotherapy treatments. Immune checkpoint inhibitors (ICIs) have demonstrated remarkable effectiveness in treating non-small cell lung cancer (NSCLC). They are currently being utilized as the initial treatment option for metastatic disease, as a consolidation therapy after chemoradiation in unresectable locally advanced disease, and as an adjuvant therapy following surgical resection and chemotherapy in resectable disease.

The initial breakthrough in utilizing ICIs for lung cancer treatment came with the introduction of the PD-1 inhibitor nivolumab. In randomized phase III trials, nivolumab demonstrated a higher objective response rate (ORR) and overall survival (OS) compared to docetaxel in patients with advanced squamous and non-squamous NSCLC who had experienced progression after platinum-based chemotherapy. Subsequently, the US FDA approved another PD-1 inhibitor, pembrolizumab, and a PD-L1 inhibitor, atezolizumab, for the same indication. These approvals were based on the superior efficacy of these agents compared to docetaxel as second-line treatments. The success of ICIs in the second-line setting opened the door for their use as first-line treatments for advanced NSCLC. In the last five years, numerous phase III clinical trials have been conducted, revealing long-lasting responses and remarkable enhancements in overall survival (OS) when using immune checkpoint inhibitors (ICI) alone or in combination with platinum-based chemotherapy, as opposed to chemotherapy alone. These findings have significantly broadened the range of first-line treatment choices available 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 CTLA-4 inhibitor ipilimumab, pembrolizumab plus platinum-based chemotherapy, atezolizumab plus platinum-based chemotherapy with or without bevacizumab (for non-squamous histology), and nivolumab plus ipilimumab plus two cycles of platinum-based chemotherapy. The choice of therapy in clinical practice is largely determined by PD-L1 expression, burden of disease, and tumor mutation profile.

[1] Mamdani H, Matosevic S, Khalid AB, Durm G, Jalal SI. Immunotherapy in Lung Cancer: Current Landscape and Future Directions. Front Immunol. 2022 Feb 9;13:823618. doi: 10.3389/fimmu.2022.823618. PMID: 35222404; PMCID: PMC8864096.