Lorlatinib is a selective, potent, brain-penetrant, third-generation ALK/ROS1 tyrosine kinase inhibitor with robust clinical activity in pts with ALK-positive (ALK+) or ROS1-positive (ROS1+) advanced NSCLC. The phase 1/2 study (NCT01970865) assessed lorlatinib in pts with ALK+ or ROS1+ NSCLC based on prior treatment. Phase 2 efficacy/safety was previously reported. Here, we present PRO results.
In this ongoing open-label, multicenter study, pts received lorlatinib 100 mg once daily. Global quality of life (QoL), pt functioning and symptoms were assessed with the European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (QLQ-C30) and the Lung Cancer 13 module (QLQ-LC13) at baseline (BL) and on day 1 of each cycle. Higher scores indicated higher functioning/QoL or greater symptom severity. Change from BL (ΔBL) was summarized; a ≥ 10-point ΔBL (improved or worsened) was considered clinically meaningful. An average of mean ΔBL was calculated for each pt across cycles to determine the proportion of pts with a clinically meaningful change.
Median treatment duration was 8.3 months. Interim PRO data were analyzed through cycle 24; the completion rate was ≥94%. Clinically meaningful improvements from BL were seen for global QoL; most pts had improved (43%) or stable (neither improved nor worsened) scores (40%). Clinically meaningful improvements occurred in functioning domains and symptoms; further details will be presented. The highest proportion of pts improved in emotional (38%), role (38%) and social (34%) functioning domains. Proportions of pts with improved/stable/worse cognitive functioning were 24%/51%/24%. Most pts had improved or stable symptom scores; the greatest proportions of pts improved for symptoms of fatigue (49%), insomnia (45%) and appetite loss (42%) on QLQ-C30 and cough (44%), pain in other parts (33%) and pain in chest (30%) on QLQ-LC13. The symptom with the greatest proportion of pts with clinically meaningful worsening was peripheral neuropathy (38%).
Lorlatinib showed favorable clinical benefit and improvements in global QoL, functioning and key NSCLC symptoms in pts with ALK+ or ROS1+ NSCLC.
Clinical trial identification
Clinical trial registration: NCT01970865.
Legal entity responsible for the study
Editorial assistance was provided by Brian Szente, PhD, of inScience Communications, Springer Healthcare (New York, NY, USA) and funded by Pfizer.
S. Peters: Consulting or advisory role: Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Roche, AstraZeneca; Speakers' bureau: AstraZeneca, Roche, Bristol-Myers Squibb, MSD, Boehringer Ingelheim. A.T. Shaw: Speakers or advisory board: Pfizer, Novartis, Genentech, Roche, Ariad, Takeda, Ignyta, Blueprint Medicines, Loxo, Daiichi Sankyo, EMD Serono, Taiho Pharmaceutical, KSQ Therapeutics, Natera; Honoraria: Pfizer, Novartis, Roche/Genentech, Foundation Medicine, Takeda; Research funding: Pfizer, Novartis, Roche/Genentech. B. Besse: Travel, accommodations, expenses: Roche, Pfizer, Bristol-Myers Squibb/Medarex, Novartis, Pierre Fabre. Institutional: Research funding: AstraZeneca, Roche/Genentech, Pfizer, Boehringer Ingelheim, Lilly, Servier, Onxeo, Bristol-Myers Squibb, Ose Pharma, Inivata, Novartis. E. Felip: Consulting or advisory role: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, GuardantHealth, MSD, Novartis, Pfizer, Roche, Takeda, Merck; Speakers' bureau: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Novartis, Pfizer, Roche. B.J. Solomon: Honoraria: Bristol-Myers Squibb, AstraZeneca; Royalty, IP Rights/Patent Holder: Veristrat (Biodesix); Travel, accommodations, expenses: AstraZeneca, Roche, Merck, Bristol-Myers Squibb, Novartis; Institutional: Speakers or advisory board: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche/Genentech, Novartis; Research funding: Pfizer. R.A. Soo: Consulting or advisory role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Taiho Pharmaceutical; Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech; Research funding: AstraZeneca. A. Bearz: Speakers' bureau: MSD, Roche, BMS, Pfizer, Takeda, Eli-Lilly, Novartis; Consultant: MSD, Roche, BMS, Pfizer, Takeda, Eli-Lilly, Novartis. S.M. Gadgeel: Consulting or advisory role: Pfizer, Genentech/Roche, Ariad, AstraZeneca, Bristol-Myers Squibb; Speakers' bureau: AstraZeneca; Travel, accommodations, expenses: Ariad/Takeda, Genentech/Roche; Institutional: Research funding: Pfizer, Clovis Oncology, Merck, Genentech/Roche, Incyte, Millennium, AstraZeneca/MedImmune, Bristol-Myers Squibb, Halozyme, Acerta Pharma, Acea Biosciences, Janssen Oncology, Novartis, Five Prime Therapeutics, OncoMed. S. Kao: Honoraria: AstraZeneca, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb: Consulting or advisory role: Pfizer, AstraZeneca, Boehringer Ingelheim; Research funding: Pfizer. T. Seto: Honoraria: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Pfizer Japan, YakultHonsha, Bristol-Myers Squibb, Kyowa Hakko Kirin, Mochida Pharmaceutical, Nippon Kayaku, Ono Pharmaceutical, Roche Singapore, Sanofi, Showa Yakuhin Kako, Taiho Pharmaceutical, Takeda Pharmaceutical; Institutional: Research funding: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Pfizer Japan, YakultHonsha, Bayer Yakuhin, Eisai, Merck Serono, Novartis Pharma, Verastem. E.T. Masters, A. Abbattista, H. Thurm, A. Reisman: Employee and stock: Pfizer. J.S. Clancy: Employee: Pfizer. D.R. Camidge: Advisor/board: Roche, G1 Therapeutics, Mersana, Takeda, AstraZeneca, Genoptix, Ignyta, Daiichi Sankyo, Hansoh, Lycera, Bio-thera, Revolution Med; Research funding: Takeda. All other authors have declared no conflicts of interest.