Abstract 1304P
Background
We report updated data with BRG vs CRZ in Asian vs non-Asian pts with ALK TKI–naive advanced ALK+ NSCLC from ALTA-1L (NCT02737501) second interim analysis (IA2).
Methods
Pts were stratified by baseline (BL) CNS metastases and prior chemotherapy (CT). All pts had brain MRI at each tumor assessment. Pts were randomized 1:1 to BRG 180 mg qd (7-day lead-in at 90 mg) or CRZ 250 mg bid. Primary endpoint: blinded independent review committee (BIRC)–assessed PFS (RECIST v1.1). Secondary endpoints by BIRC included confirmed ORR, median duration of response (mDoR) in confirmed responders, and intracranial PFS (iPFS).
Results
275 pts were randomized; 108 Asian (BRG/CRZ, n=59/49), 167 non-Asian (n=78/89); median age: Asian 55/56 y; non-Asian 60/60 y. 32/24% of Asian pts vs 22/28% of non-Asian pts received prior CT; 36/33% vs 24/28% had BL CNS metastases. As of IA2 data cutoff (28 Jun 2019), there were (BRG vs CRZ) 26 vs 31 BIRC-assessed PFS events in Asian pts and 37 vs 56 in non-Asian pts. In Asian pts, median BIRC-assessed PFS (mPFS) was 24.0 mo (95% CI 18.4–not reached [NR]) with BRG vs 11.1 mo (9.2–15.6) with CRZ (HR 0.38 [95% CI 0.22–0.65]; log-rank P=0.0006). The PFS result is also in favor of BRG in non-Asian pts. Confirmed ORR (95% CI) in Asian pts was (BRG/CRZ) 78% (65–88)/71% (57–83), P=0.3397; in non-Asian pts 71% (59–80)/56% (45–67), P=0.0556. Duration of confirmed response and iPFS were both longer for BRG in both Asian and non-Asian pts. Safety profile was similar in Asian vs non-Asian pts. Table: 1304P
| Asian | Non-Asian | |||
| BRG n=59 | CRZ n=49 | BRG n=78 | CRZ n=89 | |
| mPFS, mo 1-yr PFS, % 2-yr PFS, % | 24.0 (18.4–NRa) 77 (63–86a) 46 (30–60a) | 11.1 (9.2–15.6a) 46 (30–61a) 27 (14–42a) | 24.0 (15.0–NRa) 64 (51–74a) 50 (37–61a) | 9.4 (7.3–15.6a) 45 (34–56a) 25 (16–36a) |
| PFS HR | 0.38 (0.22–0.65a); P=0.0006b | 0.54 (0.36–0.83a); P=0.0042b | ||
| Median DoR, responders, mo | 22 (14–NRa) | 11 (9–19a) | NR (22–NRa) | 18 (9–NRa) |
| iPFS events, n (%) Median iPFS, mo 2-yr iPFS, % | 20 (34) 30 (24–32a) 57 (40–71a) | 17 (35) 24 (11–NRa) 47 (25–66a) | 20 (26) NR (NRa) 70 (57–80a) | 34 (38) NR (9.0–NRa) 50 (37–62a) |
| iPFS HR | 0.32 (0.15–0.68a); P=0.0043b | 0.43 (0.24–0.76a); P=0.0060b |
a95% CI; bLog-rank test.
Conclusions
BRG showed sustained improvement in systemic and intracranial PFS vs CRZ in Asian and non-Asian pts with ALK inhibitor–naive ALK+ NSCLC, with numerically better BIRC-assessed PFS HRs in Asian pts.
Clinical trial identification
NCT02737501; Release date: March 20, 2016.
Editorial acknowledgement
Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Legal entity responsible for the study
ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
ARIAD Pharmaceuticals, Inc., Camidge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
M-J. Ahn: Honoraria (self): AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis; Advisory/Consultancy: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis. H.R. Kim: Honoraria (self), Advisory/Consultancy: AstraZeneca, Roche, Boehringer Ingelheim. J.C-H. Yang: Honoraria (self), Advisory/Consultancy: 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-Y. Han: Honoraria (self): Roche, AstraZeneca, Takeda; Advisory/Consultancy: AstraZeneca, Lilly, Novartis, Takeda; Research grant/Funding (institution): Roche, Pfizer, ONO, Takeda. J.Y-C. Li: Honoraria (self): Roche, Pfizer, Takeda, Lilly, Boehringer Ingelheim, MSD, AstraZeneca, Novartis, Bayer, Foundation Medicine; Research grant/Funding (institution): Roche; Travel/Accommodation/Expenses: Taiho, Eisai, Sanomics & Xcelom, Roche, Takeda, AstraZeneca, MSD, Boehringer Ingelheim, Pfizer. M.J. Hochmair: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, Takeda; Advisory/Consultancy: Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche, Takeda. G-C. Chang: Honoraria (self): F. Hoffmann–La Roche, Ltd, Eli Lilly and Company Oncology, AstraZeneca, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme. A. Delmonte: Advisory/Consultancy: AstraZeneca, Boehringer Ingelheim. K.H. Lee: Honoraria (self), Advisory/Consultancy: AstraZeneca, Eli Lilly, Boehringer Ingelheim. M.R. Garcia Campelo: Honoraria (self): ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim. C. Gridelli: Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer, Roche. A. Spira: Advisory/Consultancy: ARIAD, AstraZeneca, Clovis Oncology, Roche; Speaker Bureau/Expert testimony: Roche. R. Califano: Honoraria (self), Advisory/Consultancy: AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Novartis. F. Griesinger: Advisory/Consultancy: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, ARIAD, AbbVie, Siemens, Tesaro/GSK, Amgen. S. Ghosh: Honoraria (self), Advisory/Consultancy: Pfizer, Roche, MSD, Takeda. E. Felip: Advisory/Consultancy: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, MSD, Novartis, Pfizer, Roche, Takeda, Merck. D-W. Kim: Research grant/Funding (institution): Alpha Biopharma, AstraZeneca / MedImmune, Boehringer Ingelheim, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan; Travel/Accommodation/Expenses: Amgen, Daiichi Sankyo. P. Zhang: Full/Part-time employment: Takeda. S. Popat: Research grant/Funding (institution): Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria (self): Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Advisory/Consultancy: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel/Accommodation/Expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. D.R. Camidge: Honoraria (self): 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; Research grant/Funding (self): ARIAD/Takeda.