Patient-reported outcomes in a phase II, North American study of alectinib in patients with ALK-positive, crizotinib-resistant, non-small cell lung cancer

Background In a phase II North American study (NP28761; NCT01871805), the anaplastic lymphoma kinase (ALK) inhibitor alectinib demonstrated both systemic and central nervous system (CNS) efficacy with good tolerability in patients with ALK-positive non-small cell lung cancer. We describe patient-reported outcomes (PROs) from the NP28761 study. Patients and methods PROs and health-related quality of life (HRQoL) benefits were assessed using two self-administered questionnaires (the European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire-Core (EORTC QLQ-C30), and the 13-item EORTC QLQ-lung cancer-specific module) at enrolment and every 6 weeks until week 66, disease progression or death. Results Clinically meaningful mean improvements (>= 10 point change from baseline) were observed in 10 domains, including global health status (GHS), role and social functioning, fatigue, pain, dyspnoea, and appetite loss. A clinically meaningful improvement was observed in GHS from the first assessment (6 weeks) until week 60. Alectinib demonstrated a rapid effect, with a median time to symptom improvement, using the composite endpoint of cough, dyspnoea and pain in the chest, of 1.4 months (6.1 weeks) (95% CI 1.4 to 1.6) and a median time to symptom deterioration of 5.1 months (22.1 weeks) (95% CI 2.8 to 6.8). Patients with CNS metastases at baseline experienced comparable HRQoL over the duration of the study as patients without CNS metastases. Exploratory analysis showed that the occurrence of an objective response may be associated with a better HRQoL. Conclusions Patients treated with alectinib in this phase II study achieved clinically meaningful improvements in HRQoL and symptoms and had delayed time to symptom deterioration.