ESMO open · 2026
Real-world external control arm for the single-arm LIBRETTO-001 trial of selpercatinib in RET-mutation-positive medullary thyroid cancer: RECALIB-RET.
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Hadoux J, Hernando J, Wong K H, Do Cao C, Lasolle H, Buffet C, Benisvy D, Illouz F, Schneegans O, Varnier R, Drui D, Zanetta S, Hescot S, Muller M, Nascimento C, Roudaut N, Khanal M, Zheng S, Li X, Singh R, Tian W, Afonso A S, Houot B, Borget I, Segall G
Аннотация
BACKGROUND: The single-arm phase I/II LIBRETTO-001 trial demonstrated durable efficacy with selpercatinib in patients with rearranged during transfection (RET)-mutation-positive medullary thyroid cancer (MTC). RECALIB-RET compared effectiveness outcomes using a real-world external control (EC) arm of patients with RET-mutation-positive MTC treated with standard of care (SoC) versus selpercatinib (LIBRETTO-001).
PATIENTS AND METHODS: In this retrospective study, the selpercatinib arm comprised first-line (1L) or second-and-later-line (≥2L) patients from LIBRETTO-001. The EC arm comprised SoC-treated patients, pooled across (i) the French ENDOCAN-TUTHYREF (Refractory Thyroid Tumours) database (1L and ≥2L); (ii) a chart review of European patient medical records (1L and ≥2L) and (iii) a published United States chart review (≥2L). Index treatment was cabozantinib or vandetanib (1L) and any SoC (≥2L; including multikinase inhibitor, chemotherapy or immunotherapy). The primary endpoint was progression-free survival (PFS). The safety profile of SoC in the EC arm was a secondary endpoint. Propensity score matching (PSM) balanced baseline characteristics between treatment arms.
RESULTS: Baseline characteristics of the 1L selpercatinib (n = 116) and EC (n = 107) arms were balanced; PSM reduced the sample size by <30% across arms (n = 84 per arm after PSM). 1L selpercatinib conferred statistically significant PFS benefit over SoC both pre-PSM [median: not reached (NR) versus 24.0 months; P < 0.001] and post-PSM (median: NR versus 26.1 months; P < 0.001). In ≥2L (selpercatinib, n = 179; EC, n = 51), PSM increased attrition, reducing sample sizes by 78.8% (selpercatinib) and 25.5% (EC), to n = 38 per arm. The unadjusted median PFS was significantly longer with ≥2L selpercatinib versus SoC (35.6 months versus 11.6 months; P = 0.005); the difference did not reach significance after PSM. Safety findings were consistent with previously reported findings for SoC.
CONCLUSION: Selpercatinib conferred significant PFS benefit over SoC in treatment-naïve (1L) patients with RET-mutation-positive MTC, with inconclusive results in the ≥2L setting. Matching retrospective real-world data to prospective trial data is feasible. EC arms to single-arm trials may provide evidence supporting the evaluation of comparative effectiveness.
PATIENTS AND METHODS: In this retrospective study, the selpercatinib arm comprised first-line (1L) or second-and-later-line (≥2L) patients from LIBRETTO-001. The EC arm comprised SoC-treated patients, pooled across (i) the French ENDOCAN-TUTHYREF (Refractory Thyroid Tumours) database (1L and ≥2L); (ii) a chart review of European patient medical records (1L and ≥2L) and (iii) a published United States chart review (≥2L). Index treatment was cabozantinib or vandetanib (1L) and any SoC (≥2L; including multikinase inhibitor, chemotherapy or immunotherapy). The primary endpoint was progression-free survival (PFS). The safety profile of SoC in the EC arm was a secondary endpoint. Propensity score matching (PSM) balanced baseline characteristics between treatment arms.
RESULTS: Baseline characteristics of the 1L selpercatinib (n = 116) and EC (n = 107) arms were balanced; PSM reduced the sample size by <30% across arms (n = 84 per arm after PSM). 1L selpercatinib conferred statistically significant PFS benefit over SoC both pre-PSM [median: not reached (NR) versus 24.0 months; P < 0.001] and post-PSM (median: NR versus 26.1 months; P < 0.001). In ≥2L (selpercatinib, n = 179; EC, n = 51), PSM increased attrition, reducing sample sizes by 78.8% (selpercatinib) and 25.5% (EC), to n = 38 per arm. The unadjusted median PFS was significantly longer with ≥2L selpercatinib versus SoC (35.6 months versus 11.6 months; P = 0.005); the difference did not reach significance after PSM. Safety findings were consistent with previously reported findings for SoC.
CONCLUSION: Selpercatinib conferred significant PFS benefit over SoC in treatment-naïve (1L) patients with RET-mutation-positive MTC, with inconclusive results in the ≥2L setting. Matching retrospective real-world data to prospective trial data is feasible. EC arms to single-arm trials may provide evidence supporting the evaluation of comparative effectiveness.