Safety of belotecan as second-line treatment for recurrent small cell lung cancer: A phase IIb randomized multicenter study

Abstract

Background: For extensive‐stage small cell lung cancer (ES‐SCLC) patients with progressive or recurrent disease after platinum‐based combination chemotherapy, topotecan is recommended as second‐line treatment. However, although some patients may achieve at least an objective response with topotecan, response duration is often short. Belotecan, a camptothecin derivative, inhibits topoisomerase I. Previous studies have demonstrated that belotecan has active antitumor activity against advanced SCLC and ovarian cancers. We report safety data from a phase IIb randomized multicenter study of belotecan as second‐line treatment for progressive/recurrent limited‐disease (LD)‐ or ES‐SCLC. Methods: This study, conducted from March 2010 to March 2018, was designed to prove the non‐inferiority of belotecan to topotecan. Patients with recurrent ES‐SCLC were randomized (1:1 ratio) to belotecan 0.5 mg/m2 or topotecan 1.5 mg/m2 intravenously for 5 consecutive days every 3 weeks for 6 cycles or until disease progression. Adverse events (AEs) were reported according to NCI‐CTCAE (ver. 4.0) and categorized by System Organ Class and Preferred Term. Results: Overall, 161 patients (belotecan, n=80; topotecan, n=81) were evaluable in the safety analysis set. Clinical characteristics were well balanced between the treatment arms. Although belotecan recipients received significantly more treatment cycles than topotecan recipients (p=0.0210), there were no between‐group differences in the number of patients who required dose reductions or who omitted treatment in each cycle. There were no statistically significant between‐group differences in safety results: any AEs (including grade 3 or 4 AEs), adverse drug reactions (ADRs), severe AEs (SAEs) or severe ADRs (SADRs). The most common AEs in the belotecan and topotecan groups, respectively, were decreased neutrophil count (61 patients [76.3%] vs. 67 patients [82.7%]), anemia (37 [46.3% vs. 44 [54.3%]), decreased platelet count (33 [41.3%] vs. 43 [53.1%]), nausea (35 [43.8%] vs. 30 [37.0%), and anorexia (32 [40.0% vs. 36 [44.4%]). Conclusions: Our study indicates that belotecan is a safe second‐line treatment option for patients with progressive/recurrent LD‐ or ES‐SCLC.