1360P - Updated patient-reported outcomes from the CROWN study: Analyses in first-line ALK+ patients with (w) and without (w/o) baseline brain metastases (BMs) and w or w/o central nervous system adverse events (CNS AEs)

Background

Lorlatinib (LOR) demonstrated superior systemic and intracranial efficacy and favorable patient-reported outcomes (PROs) compared with crizotinib in the phase 3 CROWN study. Here we report PROs from the 36-month follow-up analysis in LOR-treated patients (pts) w and w/o baseline BMs and w or w/o CNS AEs.

Methods

Post hoc descriptive quality of life (QoL) analyses using the EORTC QLQ-C30 and QLQ-LC13 were presented for data up to cycle 38 (data cutoff: Sep 20, 2021). Longitudinal mixed-effect models evaluated score changes from baseline; clinically meaningful improvements (CMIs) were defined as a ≥10-point change.

Results

Of 148 LOR pts, 37 had baseline BMs while 111 did not (PRO completion rate, ≥95.6%). Pts w baseline BMs had lower scores than those w/o BMs on all functioning domains. Global QoL generally improved regardless of baseline BM status, although there was a trend for greater QoL improvement in pts w baseline BMs vs those w/o: pts w baseline BMs had CMIs starting from cycle 2, whereas pts w/o BMs did not have CMIs until cycle 38. Cognitive and emotional functioning scores remained stable over time regardless of baseline BM status. For cognitive functioning, pts w BMs had small numerical improvements over time (0.6 to 4.2) while pts w/o BMs had small numerical deteriorations (−2.7 to −6.6). For emotional functioning, CMIs were more frequently observed longitudinally in pts w baseline BMs. CNS AEs in LOR pts were evaluated by the EORTC QLQ-C30 cognitive and emotional functioning PRO domains. Emotional functioning scores generally improved over time, independent of presence or absence of CNS AEs. Slight declines in cognitive functioning scores over time in pts w or w/o CNS AEs were not clinically meaningful.

Conclusions

These updated PRO results from the CROWN study continue to show the benefit of LOR in the first-line setting in ALK+ pts. Both pts w or w/o baseline BM continue to maintain/improve global QoL, emotional functioning, with generally no significant deterioration in cognitive functioning. Pts w or w/o CNS AEs had similar longitudinal patterns in PRO domains.

Clinical trial identification

NCT03052608.

Editorial acknowledgement

Editorial and medical writing support was provided by Kakoli Parai, PhD of Clinical Thinking, Inc, and was funded by Pfizer.

Legal entity responsible for the study

Pfizer.

Funding

Pfizer.

Disclosure

G. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Novartis, Lilly, Pfizer, Merck, EMD Serono, Jazz, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Takeda, AstraZeneca, EMD Serono. Q. Zhou: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, Sanofi. B.J. Solomon: Financial Interests, Invited Speaker: Roche/Genentech, Pfizer, AstraZeneca, Amgen; Financial Interests, Advisory Board: Roche/Genentech, Pfizer, Merck, Bristol Myers Squibb, AstraZeneca, Amgen, Lilly, BeiGene, D3 Bio, Takeda, Janssen; Non-Financial Interests, Member of Board of Directors: Cancer Council of Victoria, Thoracic Oncology Group of Australasia; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Pfizer, Novartis, Roche/Genentech, BeiGene, Lilly, Bristol Myers Squibb, Nuvalent. H. Le: Financial Interests, Institutional, Full or part-time Employment: Pfizer; Financial Interests, Institutional, Stocks/Shares: Pfizer. A. Reisman: Financial Interests, Institutional, Full or part-time Employment: Pfizer Inc. D. Thomaidou: Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Full or part-time Employment: Pfizer. F. Toffalorio: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. 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, Merck; Financial Interests, Advisory Role: Lilly; 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, Merck.