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Methodology
29 April 2026

Efficacy of selpercatinib as a first-line treatment for RET-fusion positive non-small-cell lung cancer: a novel two-stage Bayesian network meta-analysis

Authors: Jessica E Forsyth https://orcid.org/0000-0002-5839-9160, Manoj Khanal https://orcid.org/0000-0002-3729-3666, Urpo Kiiskinen https://orcid.org/0000-0003-0791-940X, Akkula Jyothi, Rajat Goel https://orcid.org/0000-0002-8629-6038, Tarun Puri https://orcid.org/0000-0003-2399-4362, Shijie Ren https://orcid.org/0000-0003-3568-7124, Michael D Sonksen, Xiaofei Wang https://orcid.org/0009-0005-6524-6292, and Min-Hua Jen https://orcid.org/0000-0002-4916-0107 [email protected]Author Info & Affiliations
Volume 15, Number 6
https://doi.org/10.57264/cer-2026-0006
PDFFormats

Abstract

Aim: Single-arm trial data is frequently used during the reimbursement of new oncology interventions. Evaluating treatment effects relative to multiple relevant comparators via network meta-analysis (NMA) using data from single-arm trials; however, remains a challenge. This work introduces a two-stage approach to incorporate single-arm trial data into an NMA and applies this to the LIBRETTO-001 (NCT03157128) trial where selpercatinib (a selective rearranged during transfection [RET] inhibitor) was trialed as a treatment for RET-fusion positive, nonsquamous non-small-cell lung cancer in the first line setting. Materials & methods: Using data from KEYNOTE-189 (NCT02578680) and a real-world database, a pseudo comparator arm was constructed by propensity score matching and adjusted via an acceleration factor to account for the prognostic effect of RET status. NMAs were conducted using a Bayesian random-effects model. Results: The hazard ratios of selpercatinib relative to pemetrexed + platinum-based chemotherapy (the most common comparator in the network used) were found to be 0.304 (95% credible interval [CrI] 0.165, 0.553) and 0.368 (95% CrI 0.178, 0.757) for progression-free survival and overall survival, respectively. The validation of the NMA results could be assessed for progression-free survival of selpercatinib versus pembrolizumab + pemetrexed + platinum-based chemotherapy. A good agreement with published results from the Phase III LIBRETTO-431 trial (NCT04194944) was found (0.586 [95% CrI 0.302,1.123] from the NMA vs 0.46 [95% CI 0.31, 0.70] from LIBRETTO-431 the intention to treat [pembrolizumab] population). Conclusion: The two-stage approach to incorporate single-arm trial data within NMAs is readily applicable within health technology assessment. Enabling the earlier assessment of single-arm trials, via pseudo comparator arms, will provide payers with greater confidence in anticipated treatment effects. In light of the joint clinical assessment, incorporation of single-arm trials within NMA facilitates the reporting of predicted treatment effects relative to multiple relevant comparators, which is important when considering the use of interventions for the global market.

Plain language summary: Using single-arm cancer trials to compare treatments: an example in RET-fusion positive non-small-cell lung cancer

What is this article about?

New cancer medicines are often tested in single-arm trials, where all patients receive the same treatment and there is no direct comparison group. While these studies can show how well a treatment works, they make it difficult to compare new treatments with existing options, which is important for reimbursement and decision making by healthcare payers. In this study, a new two-stage method that allows results from single-arm trials to be included in network meta-analyses is presented. Network meta-analysis is a type of analysis used to compare multiple treatments at the same time. Selpercatinib is a targeted treatment for people with a specific type of lung cancer known as RET-fusion positive non-small-cell lung cancer and a clinical trial of selpercatinib was used as an example for this method. First, a ‘pseudo’ comparison group using data from another clinical trial was created, matching patients as closely as possible to those in the selpercatinib trial. Differences in efficacy related to RET status were then simulated and compared treatments using a Bayesian statistical model.

What were the results?

Our results suggest that selpercatinib improves both the time before disease worsens and overall survival compared with standard chemotherapy. Importantly, our findings were consistent with results from a later Phase III trial, providing reassurance about the validity of the approach.

Why is this important?

This method can help decision makers assess promising cancer treatments earlier and with greater confidence, even when only single-arm trial data are available.

Supplementary Material

File (supplementary material.docx)

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