• Alexander Drilon, Geoffrey R Oxnard, Tan Daniel S W DSW From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College (A.D., E.R.) and New York University Langone Medical Center (V.V.), New Y, Herbert H F Loong, Melissa Johnson, Justin Gainor, Caroline E McCoach, Oliver Gautschi, Benjamin Besse, Byoung C Cho, Nir Peled, Jared Weiss, Yu-Jung Kim, Yuichiro Ohe, Makoto Nishio, Keunchil Park, Jyoti Patel, Takashi Seto, Tomohiro Sakamoto, Ezra Rosen, Manisha H Shah, Fabrice Barlesi, Philippe A Cassier, Lyudmila Bazhenova, Filippo De Braud, Elena Garralda, Vamsidhar Velcheti, Miyako Satouchi, Kadoaki Ohashi, Nathan A Pennell, Karen L Reckamp, Grace K Dy, Jürgen Wolf, Benjamin Solomon, Gerald Falchook, Kevin Ebata, Michele Nguyen, Binoj Nair, Edward Y Zhu, Luxi Yang, Xin Huang, Elizabeth Olek, S Michael Rothenberg, Koichi Goto, and Vivek Subbiah.
• From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College (A.D., E.R.) and New York University Langone Medical Center (V.V.), New York, and Roswell Park Comprehensive Cancer Center, Buffalo (G.K.D.) - all in New York; Dana-Farber Cancer Institute (G.R.O.) and Massachusetts General Hospital (J.G.), Boston; National Cancer Centre Singapore, Singapore (D.S.W.T.); the Chinese University of Hong Kong, Hong Kong, China (H.H.F.L.); Sarah Cannon Research Institute, Nashville (M.J.); University of California, San Francisco-Helen Diller Family Comprehensive Cancer Center, San Francisco (C.E.M.), University of California, San Diego, Moores Cancer Center, La Jolla (L.B.), and City of Hope Comprehensive Cancer Center, Duarte (K.L.R.) - all in California; University of Bern, Bern, and Cantonal Hospital of Lucerne, Lucerne - both in Switzerland (O.G.); Institut Gustave Roussy, Villejuif (B.B.), Hospital La Timone, Marseille (F.B.), and Centre Léon Bérard, Lyon (P.A.C.) - all in France; Severance Hospital, Yonsei University Health System (B.C.C.), and Samsung Medical Center, Sungkyunkwan University School of Medicine (K.P.), Seoul, and Seoul National University Bundang Hospital, Seongnam (Y.J.K.) - all in South Korea; Soroka University Medical Center, Beer-Sheva, Israel (N.P.); University of North Carolina-Chapel Hill, Chapel Hill (J. Weiss); National Cancer Center Hospital (Y.O.) and Cancer Institute Hospital of the Japanese Foundation for Cancer Research (M. Nishio), Tokyo, National Hospital Organization Kyushu Cancer Center, Fukuoka (T. Seto), Tottori University Hospital, Tottori (T. Sakamoto), Hyogo Cancer Center, Akashi (M.S.), Okayama University Hospital, Okayama (K.O.), and National Cancer Center Hospital East, Chiba (K.G.) - all in Japan; University of Chicago, Chicago (J.P.); the Ohio State University Comprehensive Cancer Center, Columbus (M.H.S.), and Cleveland Clinic, Cleveland (N.A.P.); Istituto Nazionale Tumori-National Cancer Institute, Università degli Studi di Milano, Milan (F.D.B.); Vall d'Hebron Institute of Oncology, Hospital Universitario Vall d'Hebron, Barcelona (E.G.); Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany (J. Wolf); Peter MacCallum Cancer Institute, Melbourne, VIC, Australia (B.S.); Sarah Cannon Research Institute at HealthONE, Denver (G.F.); Loxo Oncology, Stamford, CT (K.E., M. Nguyen, B.N., E.Y.Z., L.Y., X.H., E.O., S.M.R.); and the University of Texas M.D. Anderson Cancer Center, Houston (V.S.).
• N. Engl. J. Med. 2020 Aug 27; 383 (9): 813-824.

BackgroundRET fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with RET fusion-positive NSCLC, the efficacy and safety of selective RET inhibition are unknown.MethodsWe enrolled patients with advanced RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated separately in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety.ResultsIn the first 105 consecutively enrolled patients with RET fusion-positive NSCLC who had previously received at least platinum-based chemotherapy, the percentage with an objective response was 64% (95% confidence interval [CI], 54 to 73). The median duration of response was 17.5 months (95% CI, 12.0 to could not be evaluated), and 63% of the responses were ongoing at a median follow-up of 12.1 months. Among 39 previously untreated patients, the percentage with an objective response was 85% (95% CI, 70 to 94), and 90% of the responses were ongoing at 6 months. Among 11 patients with measurable central nervous system metastasis at enrollment, the percentage with an objective intracranial response was 91% (95% CI, 59 to 100). The most common adverse events of grade 3 or higher were hypertension (in 14% of the patients), an increased alanine aminotransferase level (in 12%), an increased aspartate aminotransferase level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). A total of 12 of 531 patients (2%) discontinued selpercatinib because of a drug-related adverse event.ConclusionsSelpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).Copyright © 2020 Massachusetts Medical Society.

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