The benefits of etoposide capsules as maintenance therapy for patients with extensive-stage small cell lung cancer: a prospective two-stage, two-center study

Abstract

Background: Due to the high incidence and mortality of lung cancer, and etoposide is the standard first-line chemotherapy for small cell lung cancer, to evaluate the efficacy and safety of etoposide capsules at different doses as maintenance therapy for patients with extensive-stage small cell lung cancer (ES-SCLC) who show a response to etoposide plus platinum.

Methods: The study was divided into two stages: stage I, a single-center, one-arm prospective study, and stage II, a multicenter, controlled non-randomized prospective study (patients were chosen from ClinicalTrials.gov Identifier: NCT02179528). All patients received six cycles of etoposide plus platinum. Patients who were evaluated as complete remission (CR) or partial remission (PR) entered the maintenance treatment (MT) (etoposide capsule, once a day for 20 days, every 28 days as a cycle, until disease progression). In stage I, the dose of etoposide was 25 mg; in stage II, patients were non-randomized into etoposide capsule (25 mg/50 mg) and observation groups. In this study, the primary endpoints were progression-free survival (PFS) and safety; the secondary endpoint was overall survival (OS). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v3.0.

Results: Ninety-two patients were enrolled. In stage I, the median PFS was 6.700 months (95% CI: 6.408-6.992). In stage II, the median PFS of the MT group was better than that in the NMT group (8.930 vs. 5.900 months, P=0.002). In the pooled analysis, the overall median PFS of the MT group was better than that of the NMT group (7.870 vs. 5.900 months, P=0.003). However, there was no significant difference in OS between the groups (15.030 vs. 14.330 months, P=0.813). Multivariate Cox regression analysis showed that maintenance therapy was an independent protective factor for PFS in patients with ES-SCLC.

Conclusions: Etoposide capsules as maintenance therapy significantly prolonged the PFS of patients with ES-SCLC who responded to etoposide plus platinum, with acceptable tolerability.

Keywords: Etoposide capsules; extensive-stage small cell lung cancer (ES-SCLC); maintenance treatment (MT).

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-21-106). The authors have no conflicts of interest to declare.

2021 Journal of Thoracic Disease. All rights reserved.

Figures

Figure 1

Study flowchart (stage I): randomized, single-center, one-arm, prospective study [The Affiliated Cancer Hospital of Zhengzhou University (Henan, China)]. ES-SCLC, extensive-stage small cell lung cancer; SD, stable disease; PD, progressive disease; CR, complete remission; PR, partial remission.

Figure 2

Study flowchart (stage II): nonrandomized, multicenter, controlled, prospective study; [1. Department of Thoracic Medical Oncology, Peking University Cancer Hospital (Beijing, China); 2. The Affiliated Cancer Hospital of Zhengzhou University (Henan, China)]. ES-SCLC, extensive-stage small cell lung cancer; SD, stable disease; PD, progressive disease; CR, complete remission; PR, partial remission.

Figure 3

Stage II: multicenter, nonrandomized, controlled trial (50/25 mg etoposide capsule and observation group). The median PFS was better in the maintenance group than in the nonmaintenance group (8.930 vs. 5.900 months, log-rank test P=0.002, HR: 2.272, 95% CI: 1.445–3.572). No difference was observed in the median PFS between 25 and 50 mg (9.435 vs. 7.380 months, log-rank test P>0.05). PFS, progression-free survival.

Figure 4

In the pooled analysis of stages I and II, the median PFS in the maintenance treatment group (25 mg group + 50 mg group) was better than that in the non-maintenance treatment group (observation group) (7.870 vs. 5.900 months, log-rank test P=0.003). No difference was observed in the median PFS between 25 and 50 mg (8.200 vs. 7.380 months, log-rank test P>0.05, HR: 1.450, 95% CI: 0.633–3.322). PFS, progression-free survival.

Figure 5

In the pooled analysis of stages I and II, there was no significant difference in OS between the groups (15.030 vs. 14.330 months, log-rank test P=0.813, HR: 1.054, 95% CI: 0.679–1.637). MT, maintenance treatment; NMT, non-maintenance treatment; OS, overall survival.