Abstract 1197P
Background
Lorlatinib, a 3rd-generation ALK inhibitor, significantly prolonged progression-free survival (PFS) vs crizotinib in the CROWN trial in patients with untreated ALK-positive non-small cell lung cancer (NSCLC). We report data from the Asian subgroup of CROWN.
Methods
In this ongoing phase III trial (NCT03052608), untreated patients (n = 296) with ALK-positive advanced NSCLC were randomised to lorlatinib or crizotinib, stratified by presence of brain metastases and ethnicity (Asian/non-Asian). The primary endpoint was PFS by blinded independent central review. Primary and key secondary endpoints were analysed in the Asian subgroup (unstratified analyses).
Results
In the Asian subgroup, 120 patients were randomised (59 to lorlatinib, 61 to crizotinib [1 not treated]): 48 in Japan, 21 South Korea, 20 mainland China, 16 Taiwan, 8 Singapore and 7 Hong Kong. Baseline characteristics (median age: 61 and 55 years; female: 46% and 61% for lorlatinib and crizotinib, respectively) were similar to the overall population except for a slightly greater gender imbalance between treatments. Lorlatinib prolonged PFS and increased overall and intracranial response vs crizotinib (Table). The most common any-grade adverse events (AEs) with lorlatinib were hypertriglyceridaemia (68%), hypercholesterolaemia (68%), oedema (44%) and weight increased (42%), and with crizotinib were nausea (58%), diarrhoea (58%), vomiting (45%), vision disorder (43%) and constipation (42%). Grade 3/4 AEs were reported by 78% (lorlatinib) vs 60% (crizotinib). Fewer patients had AEs leading to permanent treatment discontinuation in the lorlatinib arm (6.8%) than the crizotinib arm (11.7%). Table: 1197P
| Asian subgroup | Overall populationa | |||
| Lorlatinib (n = 59) | Crizotinib (n = 61) | Lorlatinib (n = 149) | Crizotinib (n = 147) | |
| PFS (BICR) | ||||
| HR (95% CI) | 0.44 (0.24–0.78) | 0.28 (0.19–0.41) | ||
| P-value | 0.002b | <0.001 | ||
| Event-free at 12 months,% (95% CI) | 72 (59–82) | 48 (32–62) | 78 (70–84) | 39 (30–48) |
| ORR (BICR) | ||||
| n (%) | 45 (76.3) | 35 (57.4) | 113 (75.8) | 85 (57.8) |
| 95% CI | 63.4–86.4 | 44.1–70.0 | 68.2–82.5 | 49.4–65.9 |
| Intracranial ORR (BICR) c | (n = 11) | (n = 16) | (n = 38) | (n = 40) |
| n (%) | 8 (72.7) | 4 (25.0) | 25 (65.8) | 8 (20.0) |
| 95% CI | 39.0–94.0 | 7.3–52.4 | 48.6–80.4 | 9.1–35.6 |
aShaw et al. N Engl J Med. 2020; 383:2018-2029. bNo adjustment for multiplicity. cPatients with brain metastases at baseline by neuroradiologist. BICR, blinded independent central review.
Conclusions
In the Asian subgroup, a consistent and clinically meaningful improvement in PFS was observed for lorlatinib vs crizotinib. The efficacy and safety of lorlatinib vs crizotinib in the Asian subgroup of CROWN was consistent with the overall population.
Clinical trial identification
NCT03052608.
Editorial acknowledgement
Medical writing support was provided by Annette Smith, PhD, of CMC Affinity, McCann Health Medical Communications, and was funded by Pfizer.
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
Q. Zhou: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Roche. H.R. Kim: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech. R. Soo: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pfizer, Roche/Genentech, Taiho Pharmaceutical, Yuhan, Takeda, Amgen, Lilly, Merck; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche/Genentech, Takeda, Yuhan, Amgen, Bayer, Merck; Financial Interests, Personal, Other, Research Funding: AstraZeneca, Boehringer Ingelheim. C. Chiu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharma, Lilly, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Takeda; Financial Interests, Personal, Other, Consulting or Advisory Role: Lilly, Merck Sharp & Dohme, Novartis, Roche. H. Hayashi: Financial Interests, Personal, Other, Contracted/Support Research Grant: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd. S. Teraoka: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Novartis, AstraZeneca, Taiho Pharmaceutical, Ono Pharmaceutical, Boehringer Ingelheim. Y. Goto: Financial Interests, Personal, Other, Grant support, Lecture Fees, Advisory Board Fees: Eli Lilly, Taiho Pharmaceutical, Pfizer, Novartis, Merck Sharp & Dohme, Ono Pharmaceutical, Kyorin Pharmaceutical, Bristol Myers Squibb; Financial Interests, Personal, Other, Lecture Fees and Advisory Board Fees: Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Other, Grant Support and Advisory Board Fees: Guardant Health, Daiichi Sankyo; Financial Interests, Personal, Other, Advisory Board Fees: Illumina. V.H.F. Lee: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, AstraZeneca, Takeda, Novartis, Merck Sharp & Dohme, Eli Lilly, Amgen; Financial Interests, Personal, Other, Research Support Grant: AstraZeneca, Pfizer, Varian Medical Systems. J.C.M. Ho: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Pfizer, Boehringer Ingelheim, Merck Sharp & Dohme, Eli Lilly, Bristol Myers Squibb, Novartis, Takeda; Financial Interests, Personal, Other, Grants: Roche, AstraZeneca. D. Kim: Financial Interests, Personal, Other, Travel support: Daiichi Sankyo, Amgen; 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, Advisory role (uncompensated): Amgen, AstraZeneca, BMS, Ono Pharmaceuticals, Daiichi Sankyo, GSK, Janssen, Pfizer, SK Biopharm, Takeda, Yuhan. C. Lin: Financial Interests, Personal, Other, Honoraria: Eli Lilly, Novartis, Roche; Financial Interests, Personal, Other, Consulting role: Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis; Financial Interests, Personal, Other, Travel grants: BeiGene, Eli Lilly. S. Lu: Financial Interests, Personal, Other, grants for research support: AstraZeneca, Hutchison MediPharma, BMS, Heng Rui, Roche; Financial Interests, Personal, Other, Speakers' fees: AstraZeneca, Roche, Hansoh; Financial Interests, Personal, Other, Personal fees as an advisor and consultant: AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, Roche. A. Polli: Financial Interests, Personal, Other, Full-time employee and owns stocks: Pfizer. A.M. Calella: Financial Interests, Personal, Other, Full-time employee and owns stocks: Pfizer. T.S.K. Mok: Financial Interests, Institutional, Other, Grant/research funding: AstraZeneca, Bristol Myers Squibb, Clovis Oncology, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery; Financial Interests, Personal, Other, Speakers' fees: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before January 2019), Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, InMed Medical Communication, MSD, Novartis, Pfizer, prIME Oncology, Roche/Genentech, Taiho; Financial Interests, Personal, Other, Honoraria for consultation services: AbbVie, Inc., ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca, Bayer, Boehringer Ingelheim, Blueprint Medicines Corporation, Bristol Myers Squibb, Celgene, CStone Pharmaceuticals, Daiichi Sankyo, Eli Lilly, Fishawack; Financial Interests, Personal, Other, Shareholder: Hutchison Chi-Med, Sanomics, Ltd.; Financial Interests, Personal, Advisory Board: AbbVie, Inc., ACEA Pharma, Amgen, AstraZeneca, Bayer, Blueprint Medicines Corporation, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cirina, CStone Pharmaceuticals, Daiichi Sankyo, Eli Lilly, Fishawack Facilitate, Ltd., G1 Therapeutics, Inc., GeneD. Y. Wu: Financial Interests, Personal, Other, Research Funding: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hengrui, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Other, Speakers' Bureau: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hengrui, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Hengrui, Takeda. All other authors have declared no conflicts of interest.