Surprisingly Promising Tumor Control Rate of S1 Combination with Anlotinib with Refractory Relapsed SCLC Who Failed ≥ 2 Lines Chemotherapy

Abstract

Background: Patients with refractory relapsed small cell lung cancer (SCLC) who failed more than 2 lines chemotherapy have limited options. Objective Response Rate (ORR) of Immunotherapy (CheckMate-032 and Keynote-158) was only 20%. Anlotinib is a novel TKI on multi-kinase (VEGFR, c-Kit, PDGFR, FGFR) angionesis inhibitor, had ORR of only 4.9% in ALTER1202 for the third-line and further-line treatment of SCLC. S-1, a combination of three pharmacological compounds, namely tegafur (prodrug of 5-fluorouracil), gimeracil, and oteracil potassium, is a new oral fluoropyrimidine derivative designed to enhance anticancer activity and reduce gastrointestinal toxicity, has been used for treatment of SCLC with ORR of 4% (MOLECULAR AND CLINICAL ONCOLOGY 1: 263-266, 2013). In patients without any option of systemic therapy, our clinic started combined use of these drugs. This study aimed to report the preliminary results of combined S1 and anlotinib therapy in these refractory released SCLC. Method: This study retrospectively analyzed refractory relapsed in SCLC who failed to more than 2 lines’ chemotherapy. Eligible patient must have received Anlotinib (12 mg PO QD from day 1 to 14, every 3 weeks) and S1(60mg PO Bid from day 1 to 14, every 3 weeks) combined therapy. The primary endpoints were ORR and disease control rate (DCR). The secondary endpoints were PFS, OS, and safety and tolerability. Result: A total of 12 patients were recruited from Nov 2018 in this study. There were 2 females and 10 males. The median age was 64 years (37-75 years). 6 patients had failed 2 lines of refractory diseases and 6 cases failed 3 lines’s chemotherapy. Until 31 March 31, 2019, 2, 3, 3, 2, and 2 cases had accomplished 6, 5, 4, 3, and 2 cycles, respectively. The ORR and DCR were 50% and 100%, respectively (Figure 1). The median PFS and OS were not reached at the time of data analysis. The most common Treatment-related adverse events (TRAEs) were hypertension, anorexia, fatigue, blurred vision, and hand-foot syndrome. Grade ≥3 TRAEs occurred in 5 (41.7%) of patients. Anlotinib was reduced to 8mg in 2 patients and 10mg in 3 patients due to grade 3 TRAEs. Conclusion: The study demonstrates that S1 combination with anlotinib seemed to be an effective treatment option for patients with surprisingly promising response rate in refractory relapsed SCLC. Prospective clinical trial (SALTER Trial, ClinicalTrials.gov ID: NCT03823118) is ongoing to confirm the promising results.