美国斯隆凯特林癌症纪念中心Alexander Drilon联合得克萨斯大学安德森肿瘤中心Vivek Subbiah团队研究了Selpercatinib治疗RET融合阳性非小细胞肺癌的疗效。2020年8月27日，《新英格兰医学杂志》发表了该成果。
Title: Efficacy of Selpercatinib in RET Fusion–Positive Non–Small-Cell Lung Cancer
Author: Alexander Drilon, M.D.,, Geoffrey R. Oxnard, M.D.,, Daniel S.W. Tan, M.B., B.S., Ph.D.,, Herbert H.F. Loong, M.B., B.S.,, Melissa Johnson, M.D.,, Justin Gainor, M.D.,, Caroline E. McCoach, M.D., Ph.D.,, Oliver Gautschi, M.D.,, Benjamin Besse, M.D., Ph.D.,, Byoung C. Cho, M.D., Ph.D.,, Nir Peled, M.D., Ph.D.,, Jared Weiss, M.D.,, Yu-Jung Kim, M.D., Ph.D.,, Yuichiro Ohe, M.D., Ph.D.,, Makoto Nishio, M.D.,, Keunchil Park, M.D., Ph.D.,, Jyoti Patel, M.D.,, Takashi Seto, M.D.,, Tomohiro Sakamoto, M.D.,, Ezra Rosen, M.D., Ph.D.,, Manisha H. Shah, M.D.,, Fabrice Barlesi, M.D., Ph.D.,, Philippe A. Cassier, M.D.,, Lyudmila Bazhenova, M.D.,, Filippo De Braud, M.D.,, Elena Garralda, M.D.,, Vamsidhar Velcheti, M.D.,, Miyako Satouchi, M.D., Ph.D.,, Kadoaki Ohashi, M.D., Ph.D.,, Nathan A. Pennell, M.D., Ph.D.,, Karen L. Reckamp, M.D.,, Grace K. Dy, M.D.,, Jürgen Wolf, M.D.,, Benjamin Solomon, M.B., B.S., Ph.D.,, Gerald Falchook, M.D.,, Kevin Ebata, Ph.D.,, Michele Nguyen, B.S.,, Binoj Nair, Ph.D.,, Edward Y. Zhu, Ph.D.,, Luxi Yang, M.P.H.,, Xin Huang, Ph.D.,, Elizabeth Olek, M.D.,, S. Michael Rothenberg, M.D., Ph.D.,, Koichi Goto, M.D., Ph.D.,, and Vivek Subbiah, M.D.
RET 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.
We 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.
In 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.
Selpercatinib 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.