- Email: [email protected]
II trial
abstracts
Annals of Oncology
Table: 1542P Racea AEs with >10% difference between groups, n (%)
Asian (n ¼ 108)
Non-Asian (n ¼ 161)
Hypertriglyceridemiab Edemab Peripheral neuropathyb Cognitive effectsb Weight increased Mood effectsb Fatigueb Anemia Pain in extremity
82 (75.9) 52 (48.1) 41 (38.0) 18 (16.7) 15 (13.9) 13 (12.0) 8 (7.4) 7 (6.5) 7 (6.5)
92 (57.1) 97 (60.2) 82 (50.9) 53 (32.9) 46 (28.6) 45 (28.0) 59 (36.6) 35 (21.7) 30 (18.6)
AEs reported in descending order of frequency in Asian pts. a Unspecified race (n ¼ 26) b Clustered term comprising AEs that represent similar clinical symptoms/syndromes.
.Conclusions: There were no clinically relevant differences in the AEs based on age or 1542P
Safety of lorlatinib in subgroups of patients from a phase I/II trial
1
E. Felip , B.J. Solomon2, B. Besse3, T.M. Bauer4, R.A. Soo5, D.R. Camidge6, R. Chiari7, A. Bearz8, C-C. Lin9, S.M. Gadgeel10, E-H. Tan11, T. Seto12, G.R. Oxnard13, G. Peltz14, A. Abbattista15, H. Thurm16, F. Toffalorio15, S-H.I. Ou17, A.T. Shaw18 1 Oncology Department, Vall d’Hebron Institute of Oncology, Barcelona, Spain, 2 Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, 3Department of Medicine, Gustave Roussy Cancer Campus; Paris-Sud University, Villejuif; Orsay, France, 4Medical Oncology Department, Sarah Cannon Cancer Research Institute/Tennessee Oncology, Nashville, TN, USA, 5HaematologyOncology Department, National University Hospital Singapore, Singapore, 6Medical Oncology Department, University of Colorado, Aurora, CO, USA, 7Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy, 8Department of Medical Oncology, National Institute for Cancer Research, Aviano, Italy, 9Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 10Medical Oncology Department, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA, 11Department of Medical Oncology, National Cancer Center Singapore, Singapore, 12Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan, 13Department of Medicine, DanaFarber Cancer Institute, Boston, MA, USA, 14Worldwide Safety Oncology, Pfizer Oncology, Groton, CT, USA, 15Pfizer Global Oncology Product Development-Oncology, Pfizer Oncology, Milan, Italy, 16Pfizer Global Oncology Product Development-Oncology, Pfizer Oncology, La Jolla, CA, USA, 17Heamatology/Oncology Department, University of California Irvine, Irvine, CA, USA, 18Heamatology/Oncology Department, Massachusetts General Hospital, Boston, MA, USA Background: Lorlatinib, a potent, brain-penetrant 3rd-generation (gen) ALK/ROS1 tyrosine kinase inhibitor (TKI), is approved for the treatment of patients (pts) with ALKþ metastatic NSCLC whose disease has progressed on 2nd-gen ALK TKIs. The safety profile of lorlatinib has been previously reported; treatment-related adverse events (AEs) were primarily mild–moderate in severity and manageable through dose modification or standard medical therapy. Here, we report safety data in key subgroups of pts based on age, gender and race.
Volume 30 | Supplement 5 | October 2019
gender. The frequencies of most AEs known to be associated with lorlatinib were generally lower in Asian than in non-Asian pts; however, hypertriglyceridemia was more frequently reported in Asian vs non-Asian pts. Clinical trial identification: NCT01970865. Editorial acknowledgement: Jade Drummond of inScience Communications, Springer Healthcare (Chester, UK); funded by Pfizer Inc. Legal entity responsible for the study: Pfizer Inc. Funding: Pfizer Inc. Disclosure: E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Research grant / Funding (institution): Fundaci on Merck Salud; Research grant / Funding (institution): EMD Serono. B.J. Solomon: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Eisai; Licensing / Royalties: Veristrat (Biodesix); Licensing / Royalties: UpToDate; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Institution: Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution), Institution: Pfizer; Advisory / Consultancy, Institution: Genentech. B. Besse: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Onxeo; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Inivata; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Biogen; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Spectrum Pharmaceuticals; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tiziana Therapeutics. T.M. Bauer: Full / Part-time employment: Tennessee Oncology; Full / Part-time employment: Sarah Cannon Research Institute; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Loxo Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution):
doi:10.1093/annonc/mdz260 | v633
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Methods: This analysis was based on 295 pts with ALKþ or ROS1þ advanced NSCLC, 6 CNS metastases, enrolled in the ongoing ph 1/2 trial (NCT01970865) who received lorlatinib 100 mg once daily. All causality AEs were graded per CTCAE v4.03. Data cutoff was 02 Feb 2018. Results: Of the 295 pts, 241 were aged <65 years (y) and 54 were 65 y. AEs were reported at frequencies of 99.6% and 100% in the <65 y and 65 y subgroups respectively; however, there were generally more AEs in the 65 y subgroup, e.g. anemia (<65 y: 13.7% vs 65 y: 25.9%), edema (51.5% vs 68.5%), cognitive effects (26.1% vs 40.7%), dyspnea (25.7% vs 37.0%) and fatigue (26.6% vs 35.2%). AEs were generally balanced between males (n ¼ 125) and females (n ¼ 170). Among Asian (n ¼ 108) and non-Asian (n ¼ 161) pts, AEs were reported at a similar incidence (99.1% vs 100%). Grade 3/4 and grade 5 AEs were reported, respectively, in 57.4% and 12.0% of Asian pts and 58.4% and 14.9% of non-Asian pts. There were generally more AEs in non-Asian pts (Table). With multiple dosing, there were no substantial differences in lorlatinib plasma exposure in Asian vs non-Asian pts and neither steady-state AUC nor Cmax met the threshold for dose-adjustment.
abstracts
v634 | NSCLC, Metastatic
1543P
Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK1 NSCLC in the phase II ALTA trial
D.H. Lee1, D-W. Kim2, D.R. Camidge3, C.J. Langer4, R.M. Huber5, M. Tiseo6, H.L. West7, H.J.M. Groen8, K.L. Reckamp9, M.J. Hochmair10, N.B. Leighl11, K.H. Hansen12, S.N. Gettinger13, L. Paz-Ares14, E.S. Kim15, E.F. Smit16, S-W. Kim17, Q. Ni18, P. Zhang19, M-J. Ahn20 1 Oncology, Asan Medical Center, Seoul, Republic of Korea, 2Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 3Cancer Center, University of Colorado, Aurora, CO, USA, 4Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA, 5Thoracic Oncology Centre Munich, LMU Klinikum der Universit€ at Mu¨nchen, Munich, Germany, 6Medical Oncology Unit, University Hospital of Parma, Parma, Italy, 7Oncology, Swedish Cancer Institute, Seattle, WA, USA, 8 Faculty of Medical Sciences, University of Groningen and University Medical Center Groningen, Groningen, Netherlands, 9Comprehensive Cancer Center, City of Hope, Duarte, CA, USA, 10Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria, 11Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 12Department of Oncology, Odense University Hospital, Odense, Denmark, 13Oncology, Yale Cancer Center, New Haven, CT, USA, 14Medical Oncology, University Hospital 12 De Octubre, Madrid, Spain, 15Levine Cancer Institute, Atrium Health, Charlotte, NC, USA, 16Pulmonary Diseases Dept, VU University Medical Center, Amsterdam, Netherlands, 17Medical Oncology, Asan Medical Center, Seoul, Republic of Korea, 18Biostatistics, Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, 19Clinical Research, Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, 20 Heamatology/Oncology, Samsung Medical Center, Seoul, Republic of Korea Background: We report an analysis of Asian vs non-Asian pts with CRZ-refractory, ALKþ NSCLC from ALTA (NCT02094573). Methods: Pts were stratified by presence of baseline (BL) CNS metastases and best response to prior CRZ and randomized 1:1 to BRG 90 mg qd (arm A) or 180 mg qd with a 7-day lead-in at 90 mg (arm B). Primary endpoint: Investigator-assessed confirmed ORR by RECIST v1.1. Results: 222 pts were randomized; 69 Asian (A/B, n ¼ 39/30), 153 non-Asian (n ¼ 73/ 80); median age: Asian, 50/56 y; non-Asian, 51/57 y; 85/70% vs 64/66% had BL CNS metastases. As of Sep 2017, median follow-up was 18.4/22.5 mo (A/B) in Asians vs 22.3/ 24.5 mo in non-Asians. In Asians, median IRC-assessed PFS (mo) was 9.1 (95% CI 5.6– 18.2) in A vs 15.6 (9.2–21.2) in B (HR 0.88 [95% CI 0.48–1.62]; P ¼ 0.6808); in nonAsians, PFS (A/B) was 9.9 (9.0–26.3) vs 17.9 (11.6–23.9; HR 0.72 [0.45–1.13]; P ¼ 0.1510) (Table). Of 7/2 (A/B) Asian pts with measurable BL CNS metastases, 3/1 had confirmed intracranial objective responses; in non-Asian pts with measurable BL CNS metastases, IRC-assessed iORR was 53/69% (n ¼ 19/16). In Asians (A vs B) with any BL CNS metastases, IRC-assessed median iPFS (mo) was 15.6 (5.6–18.4) vs 12.8 (7.3–21.1); in non-Asians, 12.8 (7.4–NR) vs 20.7 (11.1–NR). Most common any-grade TRAEs in Asians (20%): increased CPK and amylase; in non-Asians, nausea, diarrhea, and increased CPK. Most common grade 3 TRAEs (>3%) in Asians: increased CPK; in non-Asians, increased CPK and lipase, hypertension. Early-onset pulmonary AEs occurred in 3 (4%; 1 grade 3) Asian (Korean) and 11 (7%; 6 grade 3) non-Asian pts. Dose reductions due to AE: 7.7/30.0% in Asian pts; 7.1/28.8% in non-Asian pts; discontinuations due to AE: 7.7/16.7% in Asian pts; 10.0/20.0% in non-Asian pts. Conclusions: BRG showed comparable efficacy and acceptable safety in Asians and non-Asians in CRZ-refractory ALKþ NSCLC, with nonsignificant, numerically improved PFS at the 180-mg (with lead-in) dose. Clinical trial identification: NCT02094573. Editorial acknowledgement: Peloton Advantage, LLC, an OPEN Health Company, funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Legal entity responsible for the study: ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Funding: ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Disclosure: D.H. Lee: Honoraria (self): AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ChongKunDang, CJ Healthcare, Eli Lilly, Genexine, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm, ST Cube, Takeda. D. Kim: Research grant / Funding (institution): Alpha Biopharma, Astrazeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan. D.R. Camidge: Honoraria (self): AstraZeneca, Takeda, Genoptix, G1 Therapeutics [DSMB], Mersana Therapeutics, Roche, Ignyta, Daiichi Sankyo [ILD adjudication committee], Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med; Research grant / Funding (self): Takeda. C.J. Langer: Honoraria (self): Bristol-Myers Squibb, Eli Lilly, Roche/Genentech; Advisory / Consultancy: Abbott, ARIAD, AstraZeneca, Bayer/Onyx, Bristol-Myers Squibb, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Eli Lilly, Merck, Roche/Genentech, Takeda; Research grant / Funding (self): Advantagene, ARIAD, Celgene, Clovis Oncology, GlaxoSmithKline, Inovio, Merck, Roche/Genentech, Stemcentrx; Advisory / Consultancy: Amgen, Lilly, Peregrine Pharmaceuticals, Synta. R.M. Huber: Honoraria (self): ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche; Advisory / Consultancy: Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche; Research grant / Funding (self): Pierre Fabre. M. Tiseo: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. H.L. West: Advisory / Consultancy: AbbVie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Merck, PharmaMar, Roche/Genentech, Spectrum, Takeda; Speaker Bureau / Expert testimony: ARIAD, Bristol-Myers Squibb, Roche/Genentech. H.J.M. Groen: Advisory / Consultancy: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche/Genentech; Research grant / Funding (self): Eli Lilly, Roche. K.L. Reckamp: Advisory / Consultancy: Amgen, ARIAD, Astellas, Takeda, Tesaro; Research grant / Funding (self): Adaptimmune, ARIAD, BMS, Boehringer Ingelheim, AbbVie, Novartis, Pfizer, Roche/Genentech, Xcovery. M.J. Hochmair: Honoraria (self): AstraZeneca, Bristol-
Volume 30 | Supplement 5 | October 2019
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Pfizer; Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Institution: Ignyta; Advisory / Consultancy, Institution: Moderna Therapeutics; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medpacto, Inc.; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Leap Therapeutics; Research grant / Funding (institution): MabVax; Research grant / Funding (institution): Stemline Therapeutics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Merrimack Pharmaceuticals; Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Kolltan Pharmaceuticals; Research grant / Funding (institution): Principa Biopharma; Research grant / Funding (institution): Peleton; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Aileron Therapeutics; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Top Alliance BioScience; Research grant / Funding (institution): Janssen Pharmaceuticals; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Onyx Pharmaceuticals; Research grant / Funding (institution): Phosplati Therapeutics; Research grant / Funding (institution): Foundation Medicine. R.A. Soo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Yuhan; Honoraria (self), Advisory / Consultancy: Celgene. D.R. Camidge: Honoraria (self): Roche; Honoraria (self): G1 Therapeutics; Honoraria (self): Mersana; Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): AstraZeneca; Honoraria (self): Genoptix; Honoraria (self): Ignyta; Honoraria (self): Daiichi Sankyo; Honoraria (self): Hansoh; Honoraria (self): Lycera; Honoraria (self): Biothera; Honoraria (self): Revolution Medicines. R. Chiari: Speaker Bureau / Expert testimony: Takeda. A. Bearz: Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. C. Lin: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self): Roche; Honoraria (self), Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Blueprint Medicines; Travel / Accommodation / Expenses: Eli Lilly; Travel / Accommodation / Expenses: BeiGene. S.M. Gadgeel: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: ARIAD Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Research grant / Funding (self), Research grant / Funding (institution): Merck; Research grant / Funding (institution): Blueprint Medicines. E. Tan: Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim. T. Seto: Honoraria (self), Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Honoraria (self), Research grant / Funding (institution): Kissei Pharmaceutical; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Pfizer Japan; Honoraria (self), Research grant / Funding (institution): YakultHonsha; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Mochida Pharmaceutical; Honoraria (self): Nippon Kayaku; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Roche Singapore; Honoraria (self): Sanofi; Honoraria (self): Showa Yakuhin Kako; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Takeda Pharmaceutical; Research grant / Funding (institution): Bayer Yakuhin; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Novartis Pharma; Research grant / Funding (institution): Verastem. G.R. Oxnard: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Inivata; Advisory / Consultancy: Janssen; Advisory / Consultancy: Loxo; Honoraria (self): Foundation Medicine. G. Peltz: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. A. Abbattista: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. H. Thurm: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. F. Toffalorio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. S.I. Ou: Advisory / Consultancy, Shareholder / Stockholder / Stock options: TP Therapeutics; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Honoraria (self), Research grant / Funding (institution): Ariad Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self): Merck; Advisory / Consultancy, Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Revolution Medicines. A.T. Shaw: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self): Foundation Medicine; Honoraria (self): Guardant Health; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): ARIAD Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Ignyta; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: KSQ Therapeutics; Advisory / Consultancy: Natera; Advisory / Consultancy: Loxo Pharmaceuticals; Advisory / Consultancy: Takeda; Advisory / Consultancy: Bayer; Advisory / Consultancy: Chugai Pharma; Research grant / Funding (institution): TP Therapeutics.
Annals of Oncology
Annals of Oncology
Table: 1542P Racea AEs with >10% difference between groups, n (%)
Asian (n ¼ 108)
Non-Asian (n ¼ 161)
Hypertriglyceridemiab Edemab Peripheral neuropathyb Cognitive effectsb Weight increased Mood effectsb Fatigueb Anemia Pain in extremity
82 (75.9) 52 (48.1) 41 (38.0) 18 (16.7) 15 (13.9) 13 (12.0) 8 (7.4) 7 (6.5) 7 (6.5)
92 (57.1) 97 (60.2) 82 (50.9) 53 (32.9) 46 (28.6) 45 (28.0) 59 (36.6) 35 (21.7) 30 (18.6)
AEs reported in descending order of frequency in Asian pts. a Unspecified race (n ¼ 26) b Clustered term comprising AEs that represent similar clinical symptoms/syndromes.
.Conclusions: There were no clinically relevant differences in the AEs based on age or 1542P
Safety of lorlatinib in subgroups of patients from a phase I/II trial
1
E. Felip , B.J. Solomon2, B. Besse3, T.M. Bauer4, R.A. Soo5, D.R. Camidge6, R. Chiari7, A. Bearz8, C-C. Lin9, S.M. Gadgeel10, E-H. Tan11, T. Seto12, G.R. Oxnard13, G. Peltz14, A. Abbattista15, H. Thurm16, F. Toffalorio15, S-H.I. Ou17, A.T. Shaw18 1 Oncology Department, Vall d’Hebron Institute of Oncology, Barcelona, Spain, 2 Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, 3Department of Medicine, Gustave Roussy Cancer Campus; Paris-Sud University, Villejuif; Orsay, France, 4Medical Oncology Department, Sarah Cannon Cancer Research Institute/Tennessee Oncology, Nashville, TN, USA, 5HaematologyOncology Department, National University Hospital Singapore, Singapore, 6Medical Oncology Department, University of Colorado, Aurora, CO, USA, 7Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy, 8Department of Medical Oncology, National Institute for Cancer Research, Aviano, Italy, 9Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 10Medical Oncology Department, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA, 11Department of Medical Oncology, National Cancer Center Singapore, Singapore, 12Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan, 13Department of Medicine, DanaFarber Cancer Institute, Boston, MA, USA, 14Worldwide Safety Oncology, Pfizer Oncology, Groton, CT, USA, 15Pfizer Global Oncology Product Development-Oncology, Pfizer Oncology, Milan, Italy, 16Pfizer Global Oncology Product Development-Oncology, Pfizer Oncology, La Jolla, CA, USA, 17Heamatology/Oncology Department, University of California Irvine, Irvine, CA, USA, 18Heamatology/Oncology Department, Massachusetts General Hospital, Boston, MA, USA Background: Lorlatinib, a potent, brain-penetrant 3rd-generation (gen) ALK/ROS1 tyrosine kinase inhibitor (TKI), is approved for the treatment of patients (pts) with ALKþ metastatic NSCLC whose disease has progressed on 2nd-gen ALK TKIs. The safety profile of lorlatinib has been previously reported; treatment-related adverse events (AEs) were primarily mild–moderate in severity and manageable through dose modification or standard medical therapy. Here, we report safety data in key subgroups of pts based on age, gender and race.
Volume 30 | Supplement 5 | October 2019
gender. The frequencies of most AEs known to be associated with lorlatinib were generally lower in Asian than in non-Asian pts; however, hypertriglyceridemia was more frequently reported in Asian vs non-Asian pts. Clinical trial identification: NCT01970865. Editorial acknowledgement: Jade Drummond of inScience Communications, Springer Healthcare (Chester, UK); funded by Pfizer Inc. Legal entity responsible for the study: Pfizer Inc. Funding: Pfizer Inc. Disclosure: E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Research grant / Funding (institution): Fundaci on Merck Salud; Research grant / Funding (institution): EMD Serono. B.J. Solomon: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Eisai; Licensing / Royalties: Veristrat (Biodesix); Licensing / Royalties: UpToDate; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Institution: Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution), Institution: Pfizer; Advisory / Consultancy, Institution: Genentech. B. Besse: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Onxeo; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Inivata; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Biogen; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Spectrum Pharmaceuticals; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tiziana Therapeutics. T.M. Bauer: Full / Part-time employment: Tennessee Oncology; Full / Part-time employment: Sarah Cannon Research Institute; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Loxo Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution):
doi:10.1093/annonc/mdz260 | v633
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Methods: This analysis was based on 295 pts with ALKþ or ROS1þ advanced NSCLC, 6 CNS metastases, enrolled in the ongoing ph 1/2 trial (NCT01970865) who received lorlatinib 100 mg once daily. All causality AEs were graded per CTCAE v4.03. Data cutoff was 02 Feb 2018. Results: Of the 295 pts, 241 were aged <65 years (y) and 54 were 65 y. AEs were reported at frequencies of 99.6% and 100% in the <65 y and 65 y subgroups respectively; however, there were generally more AEs in the 65 y subgroup, e.g. anemia (<65 y: 13.7% vs 65 y: 25.9%), edema (51.5% vs 68.5%), cognitive effects (26.1% vs 40.7%), dyspnea (25.7% vs 37.0%) and fatigue (26.6% vs 35.2%). AEs were generally balanced between males (n ¼ 125) and females (n ¼ 170). Among Asian (n ¼ 108) and non-Asian (n ¼ 161) pts, AEs were reported at a similar incidence (99.1% vs 100%). Grade 3/4 and grade 5 AEs were reported, respectively, in 57.4% and 12.0% of Asian pts and 58.4% and 14.9% of non-Asian pts. There were generally more AEs in non-Asian pts (Table). With multiple dosing, there were no substantial differences in lorlatinib plasma exposure in Asian vs non-Asian pts and neither steady-state AUC nor Cmax met the threshold for dose-adjustment.
abstracts
v634 | NSCLC, Metastatic
1543P
Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK1 NSCLC in the phase II ALTA trial
D.H. Lee1, D-W. Kim2, D.R. Camidge3, C.J. Langer4, R.M. Huber5, M. Tiseo6, H.L. West7, H.J.M. Groen8, K.L. Reckamp9, M.J. Hochmair10, N.B. Leighl11, K.H. Hansen12, S.N. Gettinger13, L. Paz-Ares14, E.S. Kim15, E.F. Smit16, S-W. Kim17, Q. Ni18, P. Zhang19, M-J. Ahn20 1 Oncology, Asan Medical Center, Seoul, Republic of Korea, 2Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 3Cancer Center, University of Colorado, Aurora, CO, USA, 4Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA, 5Thoracic Oncology Centre Munich, LMU Klinikum der Universit€ at Mu¨nchen, Munich, Germany, 6Medical Oncology Unit, University Hospital of Parma, Parma, Italy, 7Oncology, Swedish Cancer Institute, Seattle, WA, USA, 8 Faculty of Medical Sciences, University of Groningen and University Medical Center Groningen, Groningen, Netherlands, 9Comprehensive Cancer Center, City of Hope, Duarte, CA, USA, 10Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria, 11Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada, 12Department of Oncology, Odense University Hospital, Odense, Denmark, 13Oncology, Yale Cancer Center, New Haven, CT, USA, 14Medical Oncology, University Hospital 12 De Octubre, Madrid, Spain, 15Levine Cancer Institute, Atrium Health, Charlotte, NC, USA, 16Pulmonary Diseases Dept, VU University Medical Center, Amsterdam, Netherlands, 17Medical Oncology, Asan Medical Center, Seoul, Republic of Korea, 18Biostatistics, Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, 19Clinical Research, Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, 20 Heamatology/Oncology, Samsung Medical Center, Seoul, Republic of Korea Background: We report an analysis of Asian vs non-Asian pts with CRZ-refractory, ALKþ NSCLC from ALTA (NCT02094573). Methods: Pts were stratified by presence of baseline (BL) CNS metastases and best response to prior CRZ and randomized 1:1 to BRG 90 mg qd (arm A) or 180 mg qd with a 7-day lead-in at 90 mg (arm B). Primary endpoint: Investigator-assessed confirmed ORR by RECIST v1.1. Results: 222 pts were randomized; 69 Asian (A/B, n ¼ 39/30), 153 non-Asian (n ¼ 73/ 80); median age: Asian, 50/56 y; non-Asian, 51/57 y; 85/70% vs 64/66% had BL CNS metastases. As of Sep 2017, median follow-up was 18.4/22.5 mo (A/B) in Asians vs 22.3/ 24.5 mo in non-Asians. In Asians, median IRC-assessed PFS (mo) was 9.1 (95% CI 5.6– 18.2) in A vs 15.6 (9.2–21.2) in B (HR 0.88 [95% CI 0.48–1.62]; P ¼ 0.6808); in nonAsians, PFS (A/B) was 9.9 (9.0–26.3) vs 17.9 (11.6–23.9; HR 0.72 [0.45–1.13]; P ¼ 0.1510) (Table). Of 7/2 (A/B) Asian pts with measurable BL CNS metastases, 3/1 had confirmed intracranial objective responses; in non-Asian pts with measurable BL CNS metastases, IRC-assessed iORR was 53/69% (n ¼ 19/16). In Asians (A vs B) with any BL CNS metastases, IRC-assessed median iPFS (mo) was 15.6 (5.6–18.4) vs 12.8 (7.3–21.1); in non-Asians, 12.8 (7.4–NR) vs 20.7 (11.1–NR). Most common any-grade TRAEs in Asians (20%): increased CPK and amylase; in non-Asians, nausea, diarrhea, and increased CPK. Most common grade 3 TRAEs (>3%) in Asians: increased CPK; in non-Asians, increased CPK and lipase, hypertension. Early-onset pulmonary AEs occurred in 3 (4%; 1 grade 3) Asian (Korean) and 11 (7%; 6 grade 3) non-Asian pts. Dose reductions due to AE: 7.7/30.0% in Asian pts; 7.1/28.8% in non-Asian pts; discontinuations due to AE: 7.7/16.7% in Asian pts; 10.0/20.0% in non-Asian pts. Conclusions: BRG showed comparable efficacy and acceptable safety in Asians and non-Asians in CRZ-refractory ALKþ NSCLC, with nonsignificant, numerically improved PFS at the 180-mg (with lead-in) dose. Clinical trial identification: NCT02094573. Editorial acknowledgement: Peloton Advantage, LLC, an OPEN Health Company, funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Legal entity responsible for the study: ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Funding: ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Disclosure: D.H. Lee: Honoraria (self): AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ChongKunDang, CJ Healthcare, Eli Lilly, Genexine, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm, ST Cube, Takeda. D. Kim: Research grant / Funding (institution): Alpha Biopharma, Astrazeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan. D.R. Camidge: Honoraria (self): AstraZeneca, Takeda, Genoptix, G1 Therapeutics [DSMB], Mersana Therapeutics, Roche, Ignyta, Daiichi Sankyo [ILD adjudication committee], Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med; Research grant / Funding (self): Takeda. C.J. Langer: Honoraria (self): Bristol-Myers Squibb, Eli Lilly, Roche/Genentech; Advisory / Consultancy: Abbott, ARIAD, AstraZeneca, Bayer/Onyx, Bristol-Myers Squibb, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Eli Lilly, Merck, Roche/Genentech, Takeda; Research grant / Funding (self): Advantagene, ARIAD, Celgene, Clovis Oncology, GlaxoSmithKline, Inovio, Merck, Roche/Genentech, Stemcentrx; Advisory / Consultancy: Amgen, Lilly, Peregrine Pharmaceuticals, Synta. R.M. Huber: Honoraria (self): ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche; Advisory / Consultancy: Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche; Research grant / Funding (self): Pierre Fabre. M. Tiseo: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. H.L. West: Advisory / Consultancy: AbbVie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Merck, PharmaMar, Roche/Genentech, Spectrum, Takeda; Speaker Bureau / Expert testimony: ARIAD, Bristol-Myers Squibb, Roche/Genentech. H.J.M. Groen: Advisory / Consultancy: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche/Genentech; Research grant / Funding (self): Eli Lilly, Roche. K.L. Reckamp: Advisory / Consultancy: Amgen, ARIAD, Astellas, Takeda, Tesaro; Research grant / Funding (self): Adaptimmune, ARIAD, BMS, Boehringer Ingelheim, AbbVie, Novartis, Pfizer, Roche/Genentech, Xcovery. M.J. Hochmair: Honoraria (self): AstraZeneca, Bristol-
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Pfizer; Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Institution: Ignyta; Advisory / Consultancy, Institution: Moderna Therapeutics; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medpacto, Inc.; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Leap Therapeutics; Research grant / Funding (institution): MabVax; Research grant / Funding (institution): Stemline Therapeutics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Merrimack Pharmaceuticals; Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Kolltan Pharmaceuticals; Research grant / Funding (institution): Principa Biopharma; Research grant / Funding (institution): Peleton; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Aileron Therapeutics; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Top Alliance BioScience; Research grant / Funding (institution): Janssen Pharmaceuticals; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Onyx Pharmaceuticals; Research grant / Funding (institution): Phosplati Therapeutics; Research grant / Funding (institution): Foundation Medicine. R.A. Soo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Yuhan; Honoraria (self), Advisory / Consultancy: Celgene. D.R. Camidge: Honoraria (self): Roche; Honoraria (self): G1 Therapeutics; Honoraria (self): Mersana; Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): AstraZeneca; Honoraria (self): Genoptix; Honoraria (self): Ignyta; Honoraria (self): Daiichi Sankyo; Honoraria (self): Hansoh; Honoraria (self): Lycera; Honoraria (self): Biothera; Honoraria (self): Revolution Medicines. R. Chiari: Speaker Bureau / Expert testimony: Takeda. A. Bearz: Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. C. Lin: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self): Roche; Honoraria (self), Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Blueprint Medicines; Travel / Accommodation / Expenses: Eli Lilly; Travel / Accommodation / Expenses: BeiGene. S.M. Gadgeel: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: ARIAD Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Research grant / Funding (self), Research grant / Funding (institution): Merck; Research grant / Funding (institution): Blueprint Medicines. E. Tan: Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim. T. Seto: Honoraria (self), Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Honoraria (self), Research grant / Funding (institution): Kissei Pharmaceutical; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Pfizer Japan; Honoraria (self), Research grant / Funding (institution): YakultHonsha; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Mochida Pharmaceutical; Honoraria (self): Nippon Kayaku; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Roche Singapore; Honoraria (self): Sanofi; Honoraria (self): Showa Yakuhin Kako; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Takeda Pharmaceutical; Research grant / Funding (institution): Bayer Yakuhin; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Novartis Pharma; Research grant / Funding (institution): Verastem. G.R. Oxnard: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Inivata; Advisory / Consultancy: Janssen; Advisory / Consultancy: Loxo; Honoraria (self): Foundation Medicine. G. Peltz: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. A. Abbattista: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. H. Thurm: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. F. Toffalorio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. S.I. Ou: Advisory / Consultancy, Shareholder / Stockholder / Stock options: TP Therapeutics; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Honoraria (self), Research grant / Funding (institution): Ariad Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self): Merck; Advisory / Consultancy, Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Revolution Medicines. A.T. Shaw: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self): Foundation Medicine; Honoraria (self): Guardant Health; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): ARIAD Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Ignyta; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: KSQ Therapeutics; Advisory / Consultancy: Natera; Advisory / Consultancy: Loxo Pharmaceuticals; Advisory / Consultancy: Takeda; Advisory / Consultancy: Bayer; Advisory / Consultancy: Chugai Pharma; Research grant / Funding (institution): TP Therapeutics.
Annals of Oncology