Indirect Treatment Comparison of Lurbinectedin vs. Other Second-Line Treatments for Small-Cell Lung Cancer

Purpose/Objective(s)

Lurbinectedin received accelerated approval from the US Food and Drug Administration in 2020 for patients with metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy based on the results of a single-arm phase 2 basket trial . In this trial, lurbinectedin demonstrated an overall response rate (ORR) of 35.2% and a median overall survival (OS) of 9.3 months. Here, we performed an indirect treatment comparison of lurbinectedin vs relevant second-line treatments for SCLC by means of a network meta-analysis (NMA).

Materials/Methods

A systematic literature review (1990–Jan 2021) identified 3 randomized controlled trials (RCTs) of second-line SCLC therapies recommended by NCCN guidelines that met the criteria for the NMA. Unanchored matching-adjusted indirect comparison (MAIC) connected Study B-005 to the network of RCTs. The RCT with the most overlap with Study B-005 was used as the target population in the base case, and a MAIC was performed to estimate the relative treatment effect of lurbinectedin vs oral topotecan (central node of the network). Relative treatment effects from the MAIC were used as direct evidence in the NMA. Analyses were conducted in a Bayesian framework for OS and ORR using a fixed-effect NMA, and relative effectiveness was assessed with hazard ratios (HR) and odds ratio.

Results

The 3 RCTs included in the NMA were Baize 2020 (carboplatin/etoposide vs oral topotecan), and Eckardt 2007 and von Pawel 2001 (oral topotecan vs IV topotecan). In the base case, Baize 2020 was the target population, which consisted only of patients with platinum-sensitive disease (chemotherapy-free interval ≥90 day); therefore, the platinum-sensitive subgroup of Study B-005 was connected to the network. In the base case analysis, the HR for OS significantly favored lurbinectedin vs oral topotecan, IV topotecan, and carboplatin/etoposide (Table). There was a significant improvement in ORR for lurbinectedin vs oral topotecan; the ORR was similar for lurbinectedin vs carboplatin/etoposide (Table). Two sensitivity analyses were also conducted.

Conclusion

In the absence of head-to-head RCTs, indirect treatment comparisons provide a means of estimating the relative efficacy of lurbinectedin vs relevant comparators for the second-line treatment of SCLC. In this NMA, lurbinectedin showed a robust survival benefit for the second-line treatment of platinum-sensitive patients with SCLC compared with platinum rechallenge and vs oral and IV topotecan. Study B-005; NCT02454972