Abstract 1104P
Background
In the randomized, phase III CROWN study, lorlatinib (LOR), a brain-penetrant third generation ALK tyrosine kinase inhibitor, showed significantly longer progression-free survival and a higher frequency intracranial response than crizotinib (CRIZ) for first-line treatment in patients with ALK+ advanced NSCLC; however, patients taking LOR had a higher incidence of grade 3-4 adverse events. Patient-reported outcomes (PROs) from CROWN (NCT03052608) were analyzed to determine the effects of LOR or CRIZ on HRQOL.
Methods
Patients were randomized to receive LOR 100 mg daily or CRIZ 250 mg twice daily until disease progression, death, withdrawal of consent, or unacceptable toxic effects. HRQOL was assessed using EQ-5D-5L visual analog scale (VAS) and index scores, stratified by the presence of brain metastases. There were no adjustments for multiple comparisons.
Results
As of September 20, 2021, among the patients in the PRO population who received LOR (n=147) or CRIZ (n=138), the mean baseline (BL) EQ VAS scores were 71.6 with LOR and 70.4 with CRIZ and BL mean index scores were 0.776 and 0.750, respectively. Patients on LOR had increased scores (EQ VAS and EQ-5D-5L index scores) from BL which was maintained throughout treatment. While there was a significant difference in EQ VAS score with LOR vs CRIZ (estimated mean difference, 4.45; 95% CI, 0.94-7.96; P=.0132), no difference was observed between treatment arms in mean EQ-5D-5L index score (P=.4781). Patients with brain metastases taking LOR had a clinically meaningful improvement in VAS score by cycle 4 that was maintained through cycle 28. Patients without brain metastases taking LOR showed a greater improvement over time in VAS scores vs CRIZ (estimated mean difference, 5.22; 95% CI, 1.35-9.09; P=.0085). No differences between treatment arms were observed in EQ VAS in patients with brain metastases. No differences in index scores between treatment arms were observed in patients with and without brain metastases.
Conclusions
Improvements in HRQOL were observed with LOR in patients with or without brain metastases. These findings support the efficacy of LOR with an additional benefit of improved HRQOL.
Clinical trial identification
NCT03052608.
Editorial acknowledgement
Editorial and medical writing support was provided by Ravi Subramanian of ClinicalThinking and was funded by Pfizer.
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
G. Liu: Financial Interests, Personal and Institutional, Invited Speaker: Pfizer Inc, AstraZeneca, Takeda; Financial Interests, Personal and Institutional, Advisory Board: Pfizer Inc, Novartis, AstraZeneca, Takeda, EMD Serono, Jass Pharmaceuticals, Merck, BMS, Roche; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Takeda; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Takeda. L. Iadeluca: Financial Interests, Personal and Institutional, Full or part-time Employment: Pfizer Inc; Financial Interests, Personal and Institutional, Stocks/Shares: Pfizer Inc. A. Reisman: Financial Interests, Institutional, Full or part-time Employment: Pfizer Inc. F. Blackhall: Financial Interests, Personal, Invited Speaker, Educational Symposium lecture: AstraZeneca; Financial Interests, Personal, Advisory Board, NTRK Advisory Board and guidelines for diagnosis: Bayer; Financial Interests, Personal, Other, IDMC Chair: AstraZeneca; Financial Interests, Personal, Advisory Board, Small cell Advisory Board Oct 2020: Amgen; Financial Interests, Personal, Invited Speaker, ESMO Satellite Symposium November 2020: Takeda; Financial Interests, Personal, Other, Consultancy for RETinhibitor development: Blueprint; Financial Interests, Personal, Other, Real world evidence research study design and analysis (EGFR): Janssen; Financial Interests, Institutional, Invited Speaker, Institutional payment for clinical trial activities: Amgen, Pfizer; Financial Interests, Institutional, Invited Speaker, Payment for clinical trial activities: Mirati; Financial Interests, Institutional, Invited Speaker, Clinical trial activities: BMS; Financial Interests, Institutional, Funding, Real world evidence research programme: Roche; Non-Financial Interests, Advisory Role, Application of genotyping platforms in lung cancer: Guardant Health; Non-Financial Interests, Advisory Role, Clinical trials of IMPs in lung cancer and translational lung cancer biomarkers: AstraZeneca. J. Mazieres: Financial Interests, Invited Speaker: Roche, AstraZeneca, BMS, MSD, Daiichi, Novartis, Amgen; Financial Interests, Advisory Board: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Lilly, Merck; Financial Interests, Research Grant: Roche, AstraZeneca, Pierre Fabre, BMS; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Sanofi, Pfizer Inc, Merck.