Patients with ALK-positive non-small cell lung cancer (NSCLC) reported similar patient-reported outcomes (PROs) with lorlatinib as crizotinib with greater improvement of symptoms with lorlatinib, according to an analysis of the phase 3 CROWN trial (ClinicalTrials.gov Identifier: NCT03052608) presented at the 2020 World Conference on Lung Cancer in Singapore.1
A total of 296 patients with stage IIB/IV ALK-positive NSCLC with no prior systemic therapy were randomly assigned to receive either lorlatinib or crizotinib. The primary endpoint of the study was progression-free survival. The researchers found that quality-of-life (QOL) measures were higher with lorlatinib than crizotinib. The present analysis includes additional PROs from the trial.
PRO measures included the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) that assessed global QOL, as well as data on functioning and symptoms that were collected at baseline and on the first day of each treatment cycle. Lorlatinib treatment resulted in higher global QOL scores compared with crizotinib (hazard ratio [HR], 4.65; 95% CI, 1.14-8.16). Several symptoms were also significantly improved with lorlatinib compared with crizotinib treatment, including fatigue (HR, -5.67; 95% CI, -9.42 to -1.92), nausea and vomiting (HR, -7.86; 95% CI, -9.86 to -5.86), insomnia (HR, -7.95; 95% CI, -11.25 to -4.64), appetite loss (HR, -9.21; 95% CI, -11.80 to -6.62), diarrhea (HR, -12.03; 95% CI, -15.49 to -8.58), and coughing (HR, -4.55; 95% CI, -8.06 to -1.03). No difference in functioning domains between lorlatinib and crizotinib — including physical, role, emotional, cognitive, and social functioning — were seen.
Time to deterioration, which was a composite of chest pain, dyspnea, and cough, was also similar between treatments, with a median of 3.3 months with lorlatinib compared with 3.7 months with crizotinib (HR, 1.09; 95% CI, 0.822-1.444; P=.07293). There was no difference between the arms in time to deterioration in global QOL, with a median of 24 months with lorlatinib compared with 12 months with crizotinib (HR, 0.92; 95% CI, 0.650-1.294; P=.3127).
The authors concluded that, “PROs were consistent with the observed safety/tolerability profile of lorlatinib relative to crizotinib.” They added that “based on efficacy and QoL data, lorlatinib may be considered as a new standard of care in untreated ALK-positive NSCLC.”
Mazieres J, Ladeluca L, Shaw AT, et al. Patient-reported outcomes from the randomized Phase 3 CROWN study of first-lien lorlatinib versus crizotinib in ALK+ NSCLC. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2020.