Pharmacotherapy for Advanced Non-Small Cell Lung Cancer with Performance Status 2 without Druggable Gene Alterations: Could Immune Checkpoint Inhibitors Be a Game Changer?

Abstract

Simple SummaryData on the efficacy and safety of pharmacotherapy for advanced non-small cell lung cancer (NSCLC) with poor performance status (PS) 2 are insufficient. Cytotoxic chemotherapy for patients with PS 2 is insufficiently effective, and there are concerns about toxicity. Immune checkpoint inhibitors are a promising treatment with the potential for less severe toxicity, but data are more limited than with cytotoxic chemotherapy. In this review article, we summarize the current evidence on pharmacotherapy for NSCLC patients with PS 2 and without druggable genetic alterations, and we discuss future perspectives and challenges. Most pivotal clinical trials in advanced non-small cell lung cancer (NSCLC) have excluded patients with poor performance status (PS), and data on the efficacy and safety of pharmacotherapy have not been fully accumulated. For NSCLC patients with PS 2 and without druggable genetic alterations, monotherapy with cytotoxic agents or carboplatin-based combination therapy is usually administered based on the results of several randomized trials. However, the evidence of cytotoxic chemotherapy for patients with PS 2 is insufficient, with limited efficacy and toxicity concerns. Immune checkpoint inhibitors (ICIs) are a promising treatment for patients with PS 2 because of lower incidence of severe toxicity compared to cytotoxic chemotherapy. Meanwhile, several reports suggest that anti-PD-1 antibodies monotherapy is less effective for patients with PS 2, especially for those with PS 2 caused by disease burden. Although the combination therapy of nivolumab and ipilimumab is a promising treatment option, there is a divergence in efficacy data between clinical trials. The standard of care for advanced NSCLC with PS 2 has not been established, and future therapeutic strategies should take into account the heterogeneity of the PS 2 population.