External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer
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Authors
Rolfo, C.Hess, L. M.
Jen, M. H.
Peterson, P.
Li, X.
Liu, H.
Lai, Y.
Sugihara, T.
Kiiskinen, U.
Vickers, A.
Summers, Yvonne J
Affiliation
Center for Thoracic Oncology at Tisch Cancer Center, Mount Sinai Health System & Icahn School of Medicine at Mount Sinai, New YorkIssue Date
2022
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Background: Data for selpercatinib [a selective REarranged during Transfection (RET) inhibitor] from a single-arm trial (LIBRETTO-001, NCT03157128) in RET-fusion-positive advanced/metastatic non-small-cell lung cancer (NSCLC) were used in combination with external data sources to estimate comparative efficacy [objective response rate (ORR), progression-free survival, and overall survival (OS)] in first- and second-line treatment settings. Methods: Patient-level data were obtained from a de-identified real-world database. Patients diagnosed with advanced/metastatic NSCLC with no prior exposure to a RET inhibitor and one or more prior line of therapy were eligible. Additionally, individual patient-level data (IPD) were obtained from the pemetrexed + platinum arm of KEYNOTE-189 (NCT03950674, first line) and the docetaxel arm of REVEL (NCT01168973, post-progression). Patients were matched using entropy balancing, doubly robust method, and propensity score approaches. For patients with unknown/negative RET status, adjustment was made using a model fitted to IPD from a real-world database. Results: In first-line unadjusted analyses of the real-world control, ORR was 87.2% for LIBRETTO-001 versus 66.7% for those with RET-positive NSCLC (P = 0.06). After adjustment for unknown RET status and other patient characteristics, selpercatinib remained significantly superior versus the real-world control for all outcomes (all P < 0.001 except unadjusted RET-fusion-positive cohort). Similarly, outcomes were significantly improved versus clinical trial controls (all P < 0.05). Conclusions: Findings suggest improvement in outcomes associated with selpercatinib treatment versus the multiple external control cohorts, but should be interpreted with caution. Data were limited by the rarity of RET, lack of mature OS data, and uncertainty from assumptions to create control arms from external data.Citation
Rolfo C, Hess LM, Jen MH, Peterson P, Li X, Liu H, et al. External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer. ESMO open. 2022 Aug 1;7(4):100551. PubMed PMID: 35930972. Epub 2022/08/06. eng.Journal
ESMO OpenDOI
10.1016/j.esmoop.2022.100551PubMed ID
35930972Additional Links
https://dx.doi.org/10.1016/j.esmoop.2022.100551Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.esmoop.2022.100551
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