Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer Journal Article
| Authors: | Drilon, A.; Oxnard, G. R.; Tan, D. S. W.; Loong, H. H. F.; Johnson, M.; Gainor, J.; McCoach, C. E.; Gautschi, O.; Besse, B.; Cho, B. C.; Peled, N.; Weiss, J.; Kim, Y. J.; Ohe, Y.; Nishio, M.; Park, K.; Patel, J.; Seto, T.; Sakamoto, T.; Rosen, E.; Shah, M. H.; Barlesi, F.; Cassier, P. A.; Bazhenova, L.; De Braud, F.; Garralda, E.; Velcheti, V.; Satouchi, M.; Ohashi, K.; Pennell, N. A.; Reckamp, K. L.; Dy, G. K.; Wolf, J.; Solomon, B.; Falchook, G.; Ebata, K.; Nguyen, M.; Nair, B.; Zhu, E. Y.; Yang, L.; Huang, X.; Olek, E.; Rothenberg, S. M.; Goto, K.; Subbiah, V. |
| Article Title: | Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer |
| Abstract: | 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 lowgrade 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.). © 2020 Massachussetts Medical Society. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; young adult; unclassified drug; major clinical study; genetics; mutation; clinical trial; constipation; fatigue; advanced cancer; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; treatment duration; pyridines; outcome assessment; follow up; antineoplastic agent; prospective study; progression free survival; phase 2 clinical trial; protein kinase inhibitor; nausea; thrombocytopenia; vomiting; carcinoma, non-small-cell lung; lung neoplasms; qt prolongation; cohort analysis; creatinine; creatinine blood level; abdominal pain; coughing; drug dose escalation; drug hypersensitivity; dyspnea; fever; lymphocytopenia; rash; protein kinase inhibitors; lung tumor; alanine aminotransferase; aspartate aminotransferase; hyponatremia; blood; lung adenocarcinoma; pyrazole derivative; multicenter study; pyrazoles; drug response; urinary tract infection; gene fusion; peripheral edema; xerostomia; open study; platinum derivative; headache; phase 1 clinical trial; aminotransferase; dry skin; protein ret; ret protein, human; proto-oncogene proteins c-ret; phosphotransferase inhibitor; pyridine derivative; programmed death 1 ligand 1; large cell neuroendocrine carcinoma; non small cell lung cancer; progression-free survival; central nervous system metastasis; intracranial pressure; oncogene ret; programmed death 1 receptor antibody; very elderly; intention to treat analysis; transaminases; humans; human; male; female; priority journal; article; squamous cell lung carcinoma; loxo-292; selpercatinib |
| Journal Title: | New England Journal of Medicine |
| Volume: | 383 |
| Issue: | 9 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2020-08-27 |
| Start Page: | 813 |
| End Page: | 824 |
| Language: | English |
| DOI: | 10.1056/NEJMoa2005653 |
| PUBMED: | 32846060 |
| PROVIDER: | scopus |
| PMCID: | PMC7506467 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2020 -- Source: Scopus |
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