Patient-reported outcomes from the randomized phase III CROWN study of first-line Lorlatinib versus in ALK+ NSCLC
Patient-reported outcomes from the phase III CROWN study showed that time to treatment deterioration (TTD) in pain in chest, dyspnea, and cough was comparable between those who received lorlatinib and patients who took crizotinib. The research was presented today at the International Association for the Study of Lung Cancer's 2020 World Conference on Lung Cancer Singapore.
Lorlatinib, a third-generation ALK inhibitor, significantly improved progression-free survival compared to crizotinib in patients with previously untreated advanced ALK-positive NSCLC.
Dr. Julien Mazieres, Toulouse University Hospital, in Toulouse, France presented the detailed results of patient reported outcomes (PROs) from his same study.
CROWN enrolled 296 patients with ALK+ NSCLC and randomly assigned each to receive either lorlatinib or crizotinib. PROs were assessed using the EORTC QLQ-C30 and QLQ-LC13, and the EQ-5D-5L—assessments used to rate the health-related quality of life (QOL) of patients with cancer participating in international clinical trials. Each patient completed an assessment on the first day of each cycle (28 days) through end of treatment. Dr. Mazieres and her team measured time to treatment deterioration (TTD) in pain in chest, dyspnea, and cough and compared these results between the two treatment arms.
Completion rates were 100% at baseline and remained high (< 96%) through cycle 18 in both treatment arms. There were no clinically meaningful or statistically significant differences between treatment arms in any functioning domain, with numerical improvements favoring lorlatinib in physical, role, emotional, and social functioning scales, and a numerical improvement favoring crizotinib for cognitive functioning.
According to Dr. Mazieres, there were statistically significant, but not clinically meaningful differences favoring lorlatinib in symptoms of fatigue, nausea and vomiting, insomnia, appetite loss, and constipation. For diarrhea there was both a clinically meaningful and statistically significant difference favoring lorlatinib.
Lung cancer symptoms improved from baseline in both treatment arms, with clinically meaningful improvements in cough as early as Cycle 2 and maintained through Cycle 18. TTD in the composite endpoint of lung cancer symptoms (cough, dyspnea, or pain in chest) was similar between treatment arms (HR 1.09; 95% CI: 0.82-1.44; 2-sided p = 0.5415). Median time to worsening of global QOL was 24.0 months for lorlatinib and 12.0 months for crizotinib (HR 0.92; 95% CI 0.65-1.29).
"Time to treatment deterioration for lung cancer symptoms was comparable between treatment arms. Improvements in lung cancer symptoms were seen early and clinically meaningful improvements in cough were detected in [patients who received] lorlatinib," Dr. Mazieres reported.
"Patient-reported outcomes in phase III CROWN support the improved PFS and are consistent with safety/tolerability of lorlatinib relative to crizotinib."