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SELECT-3: A phase i study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting

Lookup NU author(s): Professor Alastair GreystokeORCiD, Dr Noor MD Haris, Professor Ruth Plummer

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Abstract

© 2017 Cancer Research UK. All rights reserved. Background:We investigated selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective, allosteric MEK1/2 inhibitor, plus platinum-doublet chemotherapy for patients with advanced/metastatic non-small cell lung cancer.Methods:In this Phase I, open-label study (NCT01809210), treatment-naïve patients received selumetinib (50, 75, 100 mg BID PO) plus standard doses of gemcitabine or pemetrexed plus cisplatin or carboplatin. Primary objectives were safety, tolerability, and determination of recommended Phase II doses.Results:Fifty-five patients received treatment: selumetinib 50 or 75 mg plus gemcitabine/cisplatin (n=10); selumetinib 50 mg plus gemcitabine/carboplatin (n=9); selumetinib 50, 75 or 100 mg plus pemetrexed/carboplatin (n=21); selumetinib 75 mg plus pemetrexed/cisplatin (n=15). Most frequent adverse events (AEs) were fatigue, nausea, diarrhoea and vomiting. Grade ≥3 selumetinib-related AEs were reported in 30 (55%) patients. Dose-limiting toxicities (all n=1) were Grade 4 anaemia (selumetinib 75 mg plus gemcitabine/cisplatin), Grade 4 thrombocytopenia/epistaxis and Grade 4 thrombocytopenia (selumetinib 50 mg plus gemcitabine/carboplatin), Grade 4 febrile neutropenia (selumetinib 100 mg plus pemetrexed/carboplatin), and Grade 3 lethargy (selumetinib 75 mg plus pemetrexed/cisplatin). Partial responses were confirmed in 11 (20%) and unconfirmed in 9 (16%) patients.Conclusions:Standard doses of pemetrexed/carboplatin or pemetrexed/cisplatin were tolerated with selumetinib 75 mg BID. The selumetinib plus gemcitabine-containing regimens were not tolerated.

Publication metadata

Author(s): Greystoke A, Steele N, Arkenau H-T, Blackhall F, Md Haris N, Lindsay CR, Califano R, Voskoboynik M, Summers Y, So K, Ghiorghiu D, Dymond AW, Hossack S, Plummer R, Dean E

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2017

Volume: 117

Issue: 7

Pages: 938-946

Print publication date: 26/09/2017

Online publication date: 24/08/2017

Acceptance date: 20/07/2017

Date deposited: 09/08/2018

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/bjc.2017.271

DOI: 10.1038/bjc.2017.271

PubMed id: 28950288

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