Alectinib conferred longer symptom improvement than crizotinib among patients with ALK-positive non-small cell lung cancer (NSCLC), according to a phase III ALEX trial presented at the ELCC 2018 (European Lung Cancer Congress) in Geneva, Switzerland.
The phase III ALEX trial was a head-to-head comparison of the next-generation tyrosine kinase inhibitor (TKI) alectinib versus the standard of care TKI crizotinib in patients with anaplastic lymphoma kinase (ALK)-positive NSCLC, dependent on a rearrangement of the ALK gene.
Approximately 4% of NSCLC patients are ALK-positive and are at high risk of central nervous system (CNS) metastases. Alectinib improved progression-free survival and prolonged the time to CNS progression compared to crizotinib. Alectinib had a better toxicity profile than crizotinib despite a longer duration of treatment.
Patient-reported outcomes in terms of health-related quality of life and lung cancer-related symptoms with alectinib and crizotinib are reported for the first time at ELCC. The EORTC QLQ-C30 questionnaire was used to evaluate health-related quality of life and the EORTC QLQ-LC13 questionnaire was used to assess lung cancer-related symptoms.
Patients completed the questionnaires at baseline, every four weeks during treatment, within the four weeks after study withdrawal, and after disease progression. Around two-thirds of patients in both treatment groups completed the questionnaires (66% and 64% in the alectinib and crizotinib groups, respectively).
Patients in both the alectinib and crizotinib treatment groups had clinically meaningful improvements in health-related quality of life. However, there was a longer duration of improvement in health-related quality of life for patients treated with alectinib (88 weeks) compared to crizotinib (68 weeks).
For the patients with CNS metastases at baseline, a lower proportion of patients in the alectinib arm had worsening in health-related quality of life compared with crizotinib starting at week four and persisting for most assessments through week 84.
In addition, a lower proportion of these patients reported worsening in cognitive function with alectinib compared to crizotinib. Regarding lung cancer symptoms, there was a clinically meaningful improvement in both treatment arms. But the duration of improvement was longer with alectinib compared to crizotinib
Dr. Fiona Blackhall, Honorary Consultant in Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK, said, "The ALEX trial was a practice-changing study that firmly placed alectinib as a first-line palliative treatment for ALK-positive non-small-cell lung cancer patients. This secondary analysis strengthens the rationale for alectinib as the standard of care in first-line treatment."