دورية أكاديمية
Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer
| العنوان: | Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer |
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| المساهمون: | Alexander Drilon, Geoffrey R Oxnard, Daniel S W Tan, 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, Vivek Subbiah, Cho, Byoung Chul |
| بيانات النشر: | Massachusetts Medical Society |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung / drug therapy, Female, Humans, Hypertension / chemically induced, Intention to Treat Analysis, Lung Neoplasms / drug therapy, Male, Middle Aged, Mutation, Progression-Free Survival, Protein Kinase Inhibitors / administration & dosage, Protein Kinase Inhibitors / adverse effects, Proto-Oncogene Proteins c-ret / analysis, Proto-Oncogene Proteins c-ret / antagonists & inhibitors, Proto-Oncogene Proteins c-ret / genetics, Pyrazoles / administration & dosage, Pyrazoles / adverse effects, Pyridines / administration & dosage, Pyridines / adverse effects, Transaminases / blood, Treatment Outcome, Young Adult |
| الوصف: | Background: 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. Methods: 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. Results: 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. Conclusions: 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. (Funded by Loxo Oncology and others; ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0028-4793 1533-4406 |
| العلاقة: | NEW ENGLAND JOURNAL OF MEDICINE; J02371; OAK-2021-02579; https://ir.ymlib.yonsei.ac.kr/handle/22282913/183899Test; T202007215; NEW ENGLAND JOURNAL OF MEDICINE, Vol.383(9) : 813-824, 2020-08 |
| DOI: | 10.1056/NEJMoa2005653 |
| الإتاحة: | https://doi.org/10.1056/NEJMoa2005653Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/183899Test |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.7C5D9B52 |
| قاعدة البيانات: | BASE |
| تدمد: | 00284793 15334406 |
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| DOI: | 10.1056/NEJMoa2005653 |