Abstract 1302
Background
Lorlatinib, a potent, brain-penetrant 3rd-generation (gen) ALK/ROS1 tyrosine kinase inhibitor (TKI), is approved for the treatment of patients (pts) with ALK+ 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.
Methods
This analysis was based on 295 pts with ALK+ or ROS1+ advanced NSCLC, ± 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 = 125) and females (n = 170). Among Asian (n = 108) and non-Asian (n = 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.Table:
1542P
Racea | ||
---|---|---|
AEs with >10% difference between groups, n (%) | Asian (n = 108) | Non-Asian (n = 161) |
Hypertriglyceridemiab | 82 (75.9) | 92 (57.1) |
Edemab | 52 (48.1) | 97 (60.2) |
Peripheral neuropathyb | 41 (38.0) | 82 (50.9) |
Cognitive effectsb | 18 (16.7) | 53 (32.9) |
Weight increased | 15 (13.9) | 46 (28.6) |
Mood effectsb | 13 (12.0) | 45 (28.0) |
Fatigueb | 8 (7.4) | 59 (36.6) |
Anemia | 7 (6.5) | 35 (21.7) |
Pain in extremity | 7 (6.5) | 30 (18.6) |
AEs reported in descending order of frequency in Asian pts.
aUnspecified race (n = 26)
bClustered term comprising AEs that represent similar clinical symptoms/syndromes.
.Conclusions
There were no clinically relevant differences in the AEs based on age or 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): Fundación 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): 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.
Resources from the same session
2023 - Patients with brain metastases treated with afatinib in clinical practice – results from the prospective non-interventional study GIDEON
Presenter: Eckart Laack
Session: Poster Display session 1
Resources:
Abstract
1613 - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: initial Phase 1b results
Presenter: David Berz
Session: Poster Display session 1
Resources:
Abstract
2853 - Real-world implementation of sequential targeted therapies for EGFR-mutated NSCLC
Presenter: Petros Christopoulos
Session: Poster Display session 1
Resources:
Abstract
1974 - A Phase II Open-Label, Multicentre Study to Assess the Anti-tumour Activity of Afatinib in Patients with Activating Epidermal Growth Factor Receptor mutation (EGFRm) from Circulating Tumor DNA (CtDNA)
Presenter: Young-Chul Kim
Session: Poster Display session 1
Resources:
Abstract
3370 - Influence of cow’s milk on the absorption and exposure of erlotinib in NSCLC patients
Presenter: Geerten Veerman
Session: Poster Display session 1
Resources:
Abstract
5900 - PTEN loss as Predictor of Tumor Heterogeneity (TH) and Poor Prognosis in EGFR-mutant Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients (pts) Receiving Tyrosine-Kinase Inhibitors (TKIs).
Presenter: Miriam Ferrara
Session: Poster Display session 1
Resources:
Abstract
1497 - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase 2 ALTA trial
Presenter: Dae Ho Lee
Session: Poster Display session 1
Resources:
Abstract
2349 - The safety assessment of crizotinib and alectinib from real world data of 840 ALK-inhibitor naïve patients with NSCLC harboring ALK-rearrangement (WJOG9516L).
Presenter: Kei Kunimasa
Session: Poster Display session 1
Resources:
Abstract
1120 - Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): the Use Via Expanded Access to Brigatinib (UVEA-Brig) study
Presenter: Silvia Novello
Session: Poster Display session 1
Resources:
Abstract
5239 - Treatment patterns and outcomes for patients (pts) with anaplastic lymphoma kinase-positive (ALK+) advanced non-small-cell lung cancer (NSCLC) in US clinical practice
Presenter: Matthew Krebs
Session: Poster Display session 1
Resources:
Abstract