Entrectinib efficacy was established in an integrated analysis of 3 trials (ALKA-372-001 EudraCT 2012-000148-88; STARTRK-1 NCT02097810; STARTRK-2 NCT02568267) in adult pts with
Enrolled pts were NTRK and ROS1 TKI naïve with locally advanced/metastatic solid tumours or NSCLC, with/without baseline CNS metastases. Tumour response was assessed by blinded independent central review (BICR) using RECIST v1.1 after 4 wks and every 8 wks thereafter. Primary endpoints were ORR and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety.
The Asian efficacy-evaluable populations comprised 13 pts (17.6% of total population) with
Entrectinib treatment achieved high response rates with a manageable safety profile in Asian pts with NTRK-fp solid tumours or ROS1-fp NSCLC, with/without baseline CNS metastases, consistent with findings in the total populations. Median follow-up:
Efficacy parameter Overall (n=13) Intracranial (n=3)* Overall (n=41) Intracranial (n=17)* ORR, n (%); 9 (69.2); 3 (100) 32 (78.0); 7 (41.2); CR 0 2 (66.6) 5 (12.2) 3 (17.6) PR 9 (69.2) 1 (33.3) 27 (65.9) 4 (23.5) SD 0 0 2 (4.9) 0 PD 1 (7.7) 0 3 (7.3) 4 (23.5) Non-CR/non-PD 0 0 1 (2.4) 4 (23.5) Missing/unevaluable 3 (23.1) 0 3 (7.3) 2 (11.8) Median time to event, mos (95% CI) DoR in responders 10.4 (5.7–NE) 8.0−12.8† 14.9 (9.1–NE) NE (4.6–NE) PFS 14.9 (6.4–NE) 8.9−13.8† 13.6 (7.7–NE) 5.4 (2.6–15.7) OS NE (14.9–NE) – NE (28.3–NE) –
ALKA-372-001 (EudraCT 2012-000148-88); STARTRK-1 (NCT02097810); STARTRK-2 (NCT02568267).
Third-party medical writing assistance, under the direction of the authors, was provided by Cassidy Bayley, PhD, of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
D.S.W. Tan: Honoraria (self): Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli Lilly, and Loxo; Research grant/Funding (institution): Novartis, Bayer, AstraZeneca, Pfizer, GlaxoSmithKline; Travel/Accommodation/Expenses: Novartis, Boehringer Ingelheim, Celgene, Merck, Pfizer, Roche, Takeda. M-J. Ahn: Honoraria (self): AstraZeneca, Eli Lilly, Takeda, Roche, MSD; Advisory/Consultancy: AstraZeneca, Eli Lilly, Takeda, Roche, MSD, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, Alpha Pharmaceutical, Progeneer. C-H. Chiu: Honoraria (self): Pfizer, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, MSD, Novartis, Ono Pharmaceutical, Roche; Advisory/Consultancy: AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, MSD, Novartis, Ono Pharmaceutical, Roche. Y. Ohe: Honoraria (self): AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Hakko Kirin; Advisory/Consultancy: AstraZeneca, Chugai Pharmaceutical, Ono, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku; Research grant/Funding (institution): AstraZeneca, Chugai Pharmaceutical, Lilly, Ono, BMS, Kyorin, Dainippon-Sumitomo, Pfizer, Taiho Pharmaceutical, Novartis, Kissei Pharmaceutical, Ignyta, Takeda, Daiichi-Sankyo, Janssen, Loxo; Officer/Board of Directors: JSMO, JLCS. H.H.F. Loong: Advisory/Consultancy: Boehringer-Ingelheim, Celgene, Eli Lilly, Novartis, Merck, Roche, Takeda; Speaker Bureau/Expert testimony: AbbVie, Bayer, Eisai, Eli Lilly, Guardant Health, Novartis; Travel/Accommodation/Expenses: Bayer, MSD, Novartis, Pfizer; Research grant/Funding (institution): MSD, Mundipharma, Novartis. S-W. Kim: Advisory/Consultancy: AstraZeneca, Boehringer-Ingelheim, Lilly, Novartis; Research grant/Funding (self): AstraZeneca. M. Takeda: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Novartis Pharma, Ono Pharmaceutical. Y-C. Li: Advisory/Consultancy: Roche, AstraZeneca, Foundation Medicine, Boehringer Ingelheim, Lilly Oncology, Merck, Pfizer, Novartis, Takeda, MSD; Research grant/Funding (self): Roche; Travel/Accommodation/Expenses: Roche, Taiho Pharmaceutical, Eisai, Sanomic, Xcelom, Takeda, AstraZeneca, MSD, Boehringer Ingelheim, Pfizer, Mundipharma. A. Cheng: Research grant/Funding (institution): Roche. T. Hida: Honoraria (self): Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Novartis, Bristol-Meyers Squibb, Kissei Pharmaceutical, Taiho Pharmaceutical, Pfizer, MSD, Takeda; Research grant/Funding (institution): Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Novartis, Bristol-Meyers Squibb, Kissei Pharmaceutical, Taiho Pharmaceutical, Pfizer, MSD, Takeda, Merck, Abbvie, Daiichi Sankyo, Astellas, Janssen. D-W. Kim: Research grant/Funding (institution): Alpha Biopharma, Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche, Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen, Daiichi-Sankyo. N. Nogami: Honoraria (self): MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb, Ono Pharmaceutical, Kyowa Hakko Kirin, Taiho, Chugai Pharmaceutical, Eli Lilly, Boehringer Ingelheim. H. Tanaka: Honoraria (self): Pfizer, Novartis, Bristol-Myers Squibb, Eli Lilly, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Ono Pharmaceutical; Research grant/Funding (institution): Bristol-Myers Squibb, Eli Lilly, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Ono Pharmaceutical. S. Osborne, R. Freund: Full/Part-time employment: F. Hoffmann-La Roche. D. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech. T. Seto: Honoraria (self): Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Kyowa Hakko Kirin, MSD, Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, Thermo Fisher Scientific; Research grant/Funding (institution): AbbVie, AstraZeneca, Bayer Yakuhin, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Kissei Pharmaceutical, Loxo, MSD, Boehringer Ingelheim, Novartis, Pfizer, Takeda; Full/Part-time employment: Precision Medicine Asia. All other authors have declared no conflicts of interest.