Advances in monotherapy and combination therapy of S-1 for patients with advanced non-small cell lung cancer: a narrative review.

Background and Objective: Both domestically and worldwide, non-small cell lung cancer (NSCLC) remain the leading cause of cancer-related death. As a fluorouracil derivative, S-1 which shows good efficacy and with few adverse effects have been widely confirmed in many solid tumors that it can provide a glimmer of hope for advanced NSCLC patients. We performed a review to explore the results of previous clinical studies of S-1 monotherapy as well as combined therapy involving S-1 in patients with advanced NSCLC. Methods: A literature search was conducted in Medline and PubMed databases using the keywords "S-1" AND "Advanced lung cancer" OR "Pharmacological mechanism". Key Content and Findings: A number of phase II clinical studies have reported on the favorable efficacy and excellent safety profiles of S-1 monotherapy in first-line or in posterior-line treatment for advanced NSCLC. In regard to S-1 in combination with chemotherapy, a number of phase II/III clinical studies have found the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of these regimens are similar to or better than immunological monotherapy with fewer adverse effects. In the case of S-1 combined with anti-vascular therapy, a number of phase II single-arm clinical studies have found that S-1 combined with bevacizumab, anlotinib and apatinib in advanced NSCLC, exhibits higher antitumor activity, less adverse effects for patients with advanced NSCLC. A phase II single-arm clinical study of gefitinib combined with S-1 had the ORR of 85.7% in the first-line treatment of advanced NSCLC. As for the combination of S-1 and immunotherapy, preliminary results of a phase II retrospective clinical trial demonstrated that the ORR was significantly better with S-1 sequential after immune checkpoint inhibitors (ICIs) than with S-1 alone. Conclusions: The findings indicate promising effectiveness and minimal toxicity with S-1 monotherapy and S-1 containing combined therapy in patients with advanced NSCLC to provide a potential treatment option for advanced NSCLC.