Patient-Reported Outcomes From the Randomized Phase 3 CROWN Study of First-Line Lorlatinib Versus Crizotinib in Advanced ALK-Positive Non-Small Cell Lung Cancer
Mené respectivement sur 148 et 140 patients atteints d'un cancer du poumon non à petites cellules ALK+ de stade avancé, cet essai de phase III compare la toxicité, du point de vue des symptômes déclarés par les patients, du lorlatinib et du crizotinib en traitement de première ligne
Objectives : Quality of life (QoL) for patients with non-small cell lung cancer (NSCLC) is negativelyimpacted by their disease and treatment side effects. We present detailed patient-reported outcome (PRO) data from the phase 3 CROWN study, which compared lorlatinib with crizotinibin patients with previously untreated ALK-positive advanced NSCLC. Materials and Methods : PROs were assessed using the European Organisation for Research and Treatment of CancerQoL Questionnaire with Lung Cancer module. A longitudinal, random-intercept, random-slope,mixed-effect model assessed score changes from baseline up to (not including) endof treatment. Mean changes of absolute scores from baseline at each cycle were calculatedand presented up to cycle 18 (≥10-point change considered clinically meaningful). Results : In both lorlatinib (n = 148) and crizotinib (n = 140) arms, there were longitudinalimprovements across multiple functioning and symptom scores during treatment comparedwith pre-treatment. Numerical improvements for most longitudinal functioning scores(physical, role, emotional, social) favored lorlatinib; cognitive functioning favoredcrizotinib. Numerical improvements favored lorlatinib for several symptoms (fatigue,nausea and vomiting, insomnia, appetite loss, constipation, diarrhea [clinically meaningfulimprovement], and cough); peripheral neuropathy favored crizotinib. Subgroup analysesshowed PROs did not differ by presence/absence of baseline brain metastases. Conclusions : Patients receiving first-line lorlatinib or crizotinib showed improvements and delayeddeterioration in QoL, functioning, and several symptoms. Alongside the previouslyreported significantly longer progression-free survival and higher intracranial responserates for lorlatinib versus crizotinib, these data further support the use of lorlatinibover crizotinib in patients with advanced ALK-positive NSCLC with/without baseline brain metastases, and provide evidence of severalQoL improvements with lorlatinib when used in the first-line setting.
Lung Cancer 2022