Background
Phase 3, double-blind RCT; N=151; resected or definitively treated stage IB–IIIA RET fusion–positive NSCLC after curative-intent surgery or radiotherapy (plus adjuvant systemic therapy if indicated). Selpercatinib is a selective, CNS-penetrant RET inhibitor.
Results
Interventions and follow up: Arm A: Selpercatinib, oral, for up to 3 years (n=75)
Arm B: Placebo, for up to 3 years (n=76)
Primary endpoint: Investigator-assessed EFS in stage II–IIIA disease
Secondary endpoints: EFS in stage IB–IIIA, BICR-assessed EFS, OS, safety
mFollow up: 24 mo (selpercatinib) / 27 mo (placebo)
Results: 2yr EFS (stage II–IIIA, n=109): 92% vs 61%; HR 0.17, 95% CI 0.06–0.51; P<.001
2yr EFS (stage IB–IIIA, N=151): 94% vs 70%; HR 0.17, 95% CI 0.06–0.49; P<.001
EFS by BICR: consistent with investigator assessment
OS: NR (3 deaths, all in placebo group, due to disease progression)
Arm B: Placebo, for up to 3 years (n=76)
Primary endpoint: Investigator-assessed EFS in stage II–IIIA disease
Secondary endpoints: EFS in stage IB–IIIA, BICR-assessed EFS, OS, safety
mFollow up: 24 mo (selpercatinib) / 27 mo (placebo)
Results: 2yr EFS (stage II–IIIA, n=109): 92% vs 61%; HR 0.17, 95% CI 0.06–0.51; P<.001
2yr EFS (stage IB–IIIA, N=151): 94% vs 70%; HR 0.17, 95% CI 0.06–0.49; P<.001
EFS by BICR: consistent with investigator assessment
OS: NR (3 deaths, all in placebo group, due to disease progression)
Adverse events
Hepatic: grade ≥3 ALT increase 17%, grade ≥3 AST increase 19%
Most common AEs: increased ALT/AST during the treatment period
Most common AEs: increased ALT/AST during the treatment period
Conclusions
Adjuvant selpercatinib produced a large, clinically meaningful improvement in event-free survival (HR 0.17) versus placebo in early-stage RET fusion–positive NSCLC, establishing the first targeted adjuvant option for this molecular subset. OS data remain immature.
Key Limitations
Small trial (N=151) for a rare biomarker; EFS (not OS) is the primary endpoint and its surrogacy for cure is unproven. Optimal duration (3 years, chosen empirically) and benefit after therapy completion are unknown; transaminase elevations require monitoring. Median follow-up still short (~2 years).
Clinical Context
Extends RET-directed therapy from advanced disease into the curative-intent adjuvant setting; selpercatinib is already FDA-approved for advanced RET fusion–positive NSCLC. Reinforces RET fusion testing in early-stage NSCLC. Adjuvant indication not yet FDA-approved as of June 2026; presented at the 2026 ASCO Annual Meeting plenary.