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. 2023 May;12(5):e220098.
doi: 10.57264/cer-2022-0098. Epub 2023 Apr 20.

Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer

Raj Hanvesakul  1 , Badri Rengarajan  2 , Navit Naveh  3 , Anne Boccuti  3 , Julie E Park  4 , Adekemi Adeyemi  4 , Clyde Caisip  4 , Jeroen P Jansen  5 , Florence R Wilson  4
Affiliations

Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer

Raj Hanvesakul et al. J Comp Eff Res. 2023 May.

Abstract

Aim: Compare lurbinectedin versus other second-line (2L) small-cell lung cancer (SCLC) treatments. Methods: An unanchored matching-adjusted indirect comparison connected the platinum-sensitive SCLC cohort of a single-arm lurbinectedin trial to a network of three randomized controlled trials (oral and intravenous [IV] topotecan, and platinum re-challenge) identified by systematic literature review. Network meta-analysis methods estimated relative treatment effects. Results: In platinum-sensitive patients, lurbinectedin demonstrated a survival benefit and favorable safety profile versus oral and IV topotecan and platinum re-challenge (overall survival, hazard ratio [HR]: 0.43; 95% credible interval [CrI]: 0.27, 0.67; HR: 0.43; 95% CrI: 0.26, 0.70; HR: 0.42; 95% CrI: 0.30, 0.58 respectively). Conclusion: Lurbinectedin showed a robust survival benefit and favorable safety versus other SCLC treatments in 2L platinum-sensitive SCLC.

Keywords: lurbinectedin; matching-adjusted indirect comparison; network meta-analysis; platinum sensitive; small-cell lung cancer; topotecan.

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Conflict of interest statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.. Study selection flow diagram based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
A sensitivity analysis was performed with the phase II basket trial (any platinum-sensitivity population) connected via Eckardt [35], including O'Brien [34] in the network. NMA: Network meta-analysis; RCT: Randomized clinical trial; SLR: Systematic literature review.
Figure 2.
Figure 2.. Evidence networks for base case analysis in patients with platinum-sensitive disease for (A) overall response rate, overall survival, grade 3/4 anemia, grade 3/4 thrombocytopenia, and grade 3/4 neutropenia.
(B) progression-free survival. Green text indicates external trial used to connect the basket trial (Trigo 2020) to the network via an unanchored MAIC; dashed line indicates pseudo-direct evidence from the MAIC. *CTFI ≥90 d subgroup (n = 60). CTFI: Chemotherapy-free interval; IV: Intravenous; MAIC: Matching-adjusted indirect comparison.
Figure 3.
Figure 3.. Forest plot of estimated odds ratios for overall survival for the base case analysis of patients with platinum-sensitive disease.
CrI: Credible interval; HR: Hazard ratio; IV: Intravenous; OS: Overall survival.
Figure 4.
Figure 4.. Forest plot of estimated odds ratios for overall response rate for the base case analysis of patients with platinum-sensitive disease.
CrI: Credible interval; IV: Intravenous; ORR: Overall response rate.
Figure 5.
Figure 5.. Results from network meta-analysis of progression-free survival.
(A) Estimated time-varying hazard ratios and 95% credible intervals for lurbinectedin versus competing interventions and (B) estimated survival curves and 95% credible intervals for lurbinectedin and competing interventions. Dashed lines at the tail of the curves represent model extrapolations. Dotted lines indicate 95% credible intervals.
See this image and copyright information in PMC

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