LIBRETTO-432 met its primary endpoint, demonstrating a highly statistically significant improvement in investigator-assessed event-free survival in stage II–IIIA RET fusion-positive NSCLC. In the adjuvant setting, how clinically meaningful is an EFS benefit in terms of reducing recurrence risk after curative-intent therapy?

Lilly characterized the effect size as being in line with some of the most striking data for targeted adjuvant therapy in lung cancer. How does this result compare conceptually with prior adjuvant data in EGFR- or ALK-driven NSCLC?

Overall survival results trended in favor of selpercatinib but were immature at the time of analysis. How should clinicians interpret EFS improvements when OS data remain early, especially in early-stage disease where cure is possible?

LIBRETTO-432 randomized 151 patients globally in a double-blind, placebo-controlled design following surgery or radiotherapy. Given the rarity of RET fusions (1–2% of NSCLC), how challenging is it to conduct adequately powered Phase 3 trials in this molecular subset?

Selpercatinib has demonstrated central nervous system activity in advanced disease. How relevant is CNS protection in the adjuvant setting, particularly regarding time to distant CNS recurrence as a secondary endpoint?

The safety profile was consistent with previous trials, but in early-stage patients who may already be cured by surgery, tolerability thresholds are higher. How do risks such as hepatotoxicity, QT prolongation, and hypertension factor into risk-benefit assessments in this setting?

Approximately 50% of NSCLC cases harbor actionable biomarkers, yet early-stage genomic testing is not uniformly adopted. How might the LIBRETTO-432 data influence testing practices at diagnosis for stage II–IIIA patients?

If approved in the adjuvant setting, how do you foresee selpercatinib being sequenced relative to chemotherapy and immunotherapy, and could this shift the standard of care for RET fusion-positive early-stage NSCLC?