Selpercatinib in Early-Stage RET Fusion–Positive Non–Small-Cell Lung Cancer

Author(s): Yi-Long Wu, M.D.¹; Maximilian Hochmair, M.D.²; Yi Yang, M.D.³; Xue-Ning Yang, M.D.¹; Masahiro Tsuboi, M.D.⁴; Luis Paz-Ares, M.D., Ph.D.⁵; James Chih-Hsin Yang, M.D., Ph.D.⁶; Lin Wu, M.D.⁷; Hye Ryun Kim, M.D., Ph.D.⁸; Damian T. Rieke, M.D.⁹; Melissa Johnson, M.D.¹⁰; Benjamin Besse, M.D., Ph.D.¹¹; Nivedita Sharma, M.D.¹²; Patricia Maeda, M.D.¹²; Patrick Peterson, Ph.D.¹²; Boris Kin Lin, M.D., Ph.D.¹²; Bente Frimodt-Moller, M.Sc.¹³; Jonathan Goldman, M.D.¹⁴; Alexander Drilon, M.D.¹⁵; the LIBRETTO-432 Trial Investigators†;

Source: DOI: 10.1056/NEJMoa2602628

Dr. Maen Hussein's Thoughts

109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib and 61% with placebo (HR for disease recurrence, progression, or death, 0.17 P<0.001). Patients with stage IB, II, or IIIA non–small-cell lung cancer (NSCLC), event-free survival at 2 years was 94% with selpercatinib and 70% with placebo. Genomic testing is expanding now for early stage NSCLC. More study in the adjuvant setting showing promise with targeted therapy.

BACKGROUND

Selpercatinib, a highly selective, potent, and central nervous system–penetrant RET inhibitor, is approved for RET fusion–positive advanced or metastatic non–small-cell lung cancer (NSCLC). The efficacy and safety of selpercatinib in early-stage NSCLC are unknown.

METHODS

We conducted a phase 3, double-blind trial involving patients with RET fusion–positive NSCLC who had received definitive therapy with curative intent (surgery or radiotherapy with adjuvant systemic anticancer therapy, if applicable). Patients were randomly assigned to receive adjuvant selpercatinib or placebo for up to 3 years. The primary end point was investigator-assessed event-free survival in patients with stage II or IIIA disease. Secondary end points were investigator-assessed event-free survival in patients with stage IB, II, or IIIA disease; event-free survival as assessed by blinded independent central review; overall survival; and safety. Research Summary Selpercatinib in Early-Stage RET Fusion–Positive NSCLC

RESULTS

A total of 151 patients were assigned to receive selpercatinib (75 patients) or placebo (76 patients). Median follow-up was 24 months and 27 months in the respective groups. Among 109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib and 61% with placebo (hazard ratio for disease recurrence, progression, or death, 0.17; 95% confidence interval [CI], 0.06 to 0.51; P

CONCLUSIONS

Among patients with stage II or IIIA RET fusion–positive NSCLC, event-free survival was significantly longer with adjuvant selpercatinib than with placebo. (Funded by Lilly; LIBRETTO-432 ClinicalTrials.gov number, NCT04819100.) Quick Take Adjuvant Selpercatinib in RET Fusion–Positive NSCLC 2m 33s

Author Affiliations

¹Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China; ²Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna; ³Department of Thoracic Surgery, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Third People’s Hospital of Chengdu, Chengdu, China; ⁴National Cancer Center Hospital East, Kashiwa, Japan; ⁵Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid; ⁶National Taiwan University Hospital, NTU Cancer Center, Taipei; ⁷Hunan Cancer Hospital, Changsha, China; ⁸Division of Medical Oncology, Department of Internal Medicine, Yonsei University Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; ⁹Charité–Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin; ¹⁰Sarah Cannon Research Institute, Nashville; ¹¹Paris Saclay University, Gustave Roussy, Villejuif, France; ¹²Lilly, Indianapolis; ¹³Lilly, Copenhagen; ¹⁴University of California, Los Angeles, Los Angeles; ¹⁵Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York

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