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ePoster Display

1195P - Brigatinib (BRG) vs crizotinib (CRZ) in ALK TKI–naive ALK+ NSCLC: Final results from ALTA-1L

Date

16 Sep 2021

Session

ePoster Display

Presenters

Sanjay Popat

Citation

Annals of Oncology (2021) 32 (suppl_5): S949-S1039. 10.1016/annonc/annonc729

Authors

S. Popat1, H.R. Kim2, M. Ahn3, J.C. Yang4, J. Han5, M.J. Hochmair6, K.H. Lee7, A. Delmonte8, M.R. Garcia Campelo9, D. Kim10, F. Griesinger11, E. Felip12, R. Califano13, A. Spira14, S.N. Gettinger15, M. Tiseo16, H.M. Lin17, Y. Liu17, F. Vranceanu18, D..R. Camidge19

Author affiliations

  • 1 Medicine, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 2 Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 3 Division Of Hematology-oncology, Samsung Medical Center, Seoul/KR
  • 4 Department Of Medical Oncology, National Taiwan University Cancer Center, Taipei/TW
  • 5 Cancer Center, National Cancer Center, Goyang/KR
  • 6 Department Of Respiratory And Critical Care Medicine, Klinik Floridsdorf, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Vienna/AT
  • 7 Division Of Medical Oncology, Chungbuk National University Hospital, Cheongju/KR
  • 8 Medical Oncology, Scientific Institute of Romagna for the Study and Treatment of Cancer, Meldola/IT
  • 9 Dept. Medical Oncology, University Hospital A Coruña, A Coruña/ES
  • 10 Internal Medicine, Seoul National University Hospital, 03080 - Seoul/KR
  • 11 Pius-hospital Oldenburg, University of Oldenburg, Oldenburg/DE
  • 12 Medical Oncology Service (lung Cancer Unit), Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 13 Department Of Medical Oncology, The Christie NHS Foundation Trust, Manchester/GB
  • 14 Medical Oncology, Virginia Cancer Specialists Research Institute, Fairfax/US
  • 15 Medical Oncology, Yale Cancer Center, New Haven/US
  • 16 Medical Oncology Unit, University Hospital of Parma, Parma/IT
  • 17 Global Evidence And Outcome, Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge/US
  • 18 Clinical Science, Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge/US
  • 19 Medical Oncology, University of Colorado Cancer Center, 80045 - Aurora/US
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Abstract 1195P

Background

In 2 planned interim analyses of ALTA-1L (NCT02737501), BRG BIRC-assessed PFS was superior to CRZ. We report final ALTA-1L results.

Methods

Patients (pts) with ALK TKI–naive advanced ALK+ NSCLC were enrolled and stratified by baseline (BL) brain metastases (BM) and prior chemotherapy (CT). One prior CT for advanced NSCLC and asymptomatic BM was allowed. Pts were randomized 1:1 to BRG 180 mg qd (7-day lead-in at 90 mg) or CRZ 250 mg BID. Pts in the CRZ arm were offered BRG at progression. Primary endpoint: BIRC-assessed PFS (RECIST v1.1). Secondary endpoints included confirmed iORR, iPFS by BIRC, OS, safety, and QoL.

Results

275 pts randomized (BRG/CRZ, n=137/138); median age 58/60 y; prior CT 26%/27%; BL BM 29%/30%. As of 29 Jan 2021 (last patient contact), median follow-up was (BRG/CRZ): 40.4/15.2 mo, with 166 (73/93) PFS events. BIRC-assessed PFS HR was 0.48 (95% CI: 0.35–0.66, log-rank P<0.0001); BRG mPFS was 24.0 mo (95% CI: 18.4–43.2) vs CRZ 11.1 mo (95% CI: 9.1–13.0); 3-yr PFS rate was (BRG/CRZ) 43%/19%. Investigator-assessed PFS HR was 0.43 (95% CI: 0.31–0.58, mPFS 30.8 vs 9.2 mo). mDoR (BIRC) was 33/14 mo. Median OS was not reached in either group (events BRG/CRZ: 41/51; HR: 0.81 [95% CI: 0.53–1.22]; log rank P=0.3311); 3-yr OS was 71%/68%. In pts with BL BM, OS HR was 0.43 (95% CI: 0.21–0.89; Table); in pts with no BL BM, 1.16 (0.69–1.93). Most common grade ≥3 TEAEs: BRG: increased CPK (26%) and lipase (15%), hypertension (14%); CRZ: increased ALT (10%), lipase, (8%), AST (7%). Any grade ILD/pneumonitis (BRG/CRZ): 4.4%/2.2%; discontinuation due to AE: 13.2%/8.8%. Median time to worsening in pt-reported global health status/QoL was (BRG/CRZ) 26.7/8.3 mo; HR: 0.69 (95% CI: 0.49–0.98). Table: 1195P

Efficacy per BIRC BRG CRZ P
BL brain metastases
any, n 40 a 41a
PFS events, n (%) 24 (60) 31 (76)
HR 0.25 (0.14–0.46b) <0.0001c
OS events, n (%) 11 (28) 22 (54)
3-yr OS, % 74 (57–85b) 55 (38–69b)
HR 0.43 (0.21–0.89b) 0.0199c
47d 49d
None, n 97a 97a
PFS events, n (%) 49 (51) 62 (64)
HR 0.62 (0.43–0.91b) 0.0131c
90d 89d
iPFS events, n (%) 25 (28) 23 (26)
HR 0.70 (0.39–1.26b) 0.2410c
Measurable, n 18 23
iORRe, % 78 (52–94b) 30 (13–53b) 0.0036f
Confirmed iORR, % 78 (52–94b) 26 (10–48b) 0.0014f
Median iDoRg, mo 28 (6–NEb) 9 (4–NEb)

aPer investigator; b95% CI; cLog-rank; dPer BIRC; eResponse,≥1 assessment; fCochran-Mantel-Haenszel test; gConfirmed responders

Conclusions

BRG demonstrated durable overall and intracranial efficacy, and the tolerability profile remained consistent and manageable despite extended treatment duration, confirming BRG as an effective standard-of-care treatment in pts with treatment-naive ALK+ NSCLC.

Clinical trial identification

NCT02737501; Release date: 30 March 2016.

Editorial acknowledgement

Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Inc.

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

S. Popat: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Guardant Health, Janssen, Lilly, Merck KGaA, Novartis, Roche, Takeda; Financial Interests, Institutional, Other, Sub-investigator: Amgen, MSD; Financial Interests, Institutional, Other, Coordinating PI: ARIAD, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics; Financial Interests, Institutional, Other, Local PI: AstraZeneca, GlaxoSmithKline, Roche, Trizel; Non-Financial Interests, Personal, Officer: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role: British Thoracic Oncology Group, European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role: ALK Positive UK, International Association for the Study of Lung Cancer, Lung Cancer Europe, Ruth Strauss Foundation; Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation. H.R. Kim: Financial Interests, Personal, Other, Honoraria, consulting or advisory role: AstraZeneca, Roche, Boehringer Ingelheim. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis; Financial Interests, Personal, Other, consulting or advisory role: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis. J.C. Yang: Financial Interests, Personal, Other, Honoraria or advisory role: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, Daiichi Sankyo, Takeda, AstraZeneca, Hansoh Pharmaceuticals. J. Han: Financial Interests, Personal, Other, Research funding: Roche. M.J. Hochmair: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, Takeda; Financial Interests, Personal, Other, consulting or advisory role: Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche, Takeda. K.H. Lee: Financial Interests, Personal, Other, Honoraria, advisory role: AstraZeneca, Eli Lilly, Boehringer Ingelheim. A. Delmonte: Financial Interests, Personal, Other, Consulting/advisory role: AstraZeneca, Boehringer Ingelheim. M.R. Garcia Campelo: Financial Interests, Personal, Invited Speaker, Consulting/advisory role: Takeda, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim, Pfizer, Janssen, Eli Lilly, MSD, Sanofi. D. Kim: Financial Interests, Institutional, Other, Research funding: Alpha Biopharma, Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge B; Financial Interests, Personal, Other, travel/accommodations: Amgen, Daiichi Sankyo. F. Griesinger: Financial Interests, Personal, Other, Consulting or advisory role: ARIAD, Takeda, Roche, Novartis, Pfizer. E. Felip: Financial Interests, Personal, Other, Consulting/advisory role: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, MSD, Novartis, Pfizer, Roche, Takeda, Merck. R. Califano: Financial Interests, Personal, Other, Honoraria and consulting or advisory role: AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Novartis. A. Spira: Financial Interests, Personal, Other, Consulting/advisory role: ARIAD, AstraZeneca, Clovis Oncology, Roche, Amgen, Mirati, BMS, Merck. S.N. Gettinger: Financial Interests, Personal, Invited Speaker, Consulting or advisory role: ARIAD, BMS, Janssen; Financial Interests, Personal, Other, Research funding: ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech. M. Tiseo: Financial Interests, Personal, Other, Speakers bureau or advisory role: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. H.M. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. Y. Liu: Financial Interests, Personal, Full or part-time Employment: Takeda. F. Vranceanu: Financial Interests, Personal, Full or part-time Employment: Takeda. D.R. Camidge: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Ignyta, Daiichi Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis; Financial Interests, Personal, Funding, Research funding: ARIAD/Takeda.

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