Alectinib provides longer symptom improvement than crizotinib in <em>ALK</em>-positive non–small cell lung cancer (NSCLC), according to results from the ALEX trial presented by Pérol et al at the European Lung Cancer Congress (ELCC) in Geneva, Switzerland (Abstract 138PD_PR).
The phase III ALEX trial was a head-to-head comparison of the next-generation tyrosine kinase inhibitor alectinib (Alecensa) vs the standard of care tyrosine kinase inhibitor crizotinib (Xalkori) 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, according to a report by Peters et al in The New England Journal of Medicine.
Patient-reported outcomes in terms of health-related quality of life and lung cancer–related symptoms with alectinib and crizotinib were 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 4 weeks during treatment, within the 4 weeks after study withdrawal, and after disease progression. The reasons for withdrawal have been previously reported by Peters et al; very few were due to symptom deterioration in either group.
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 4 (10.8% vs. 20.6%) and persisting for most assessments through week 84 (0% vs 16.7 %). In addition, a lower proportion of these patients reported worsening in cognitive function with alectinib compared to crizotinib (17.9% vs 34.6% at week 32, respectively).
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 (cough: 96 vs 84 weeks; chest pain: 96 vs 80 weeks; fatigue: 96 vs 68 weeks; pain in other parts: 96 vs 68 weeks, respectively).
Fewer patients in the alectinib group reported a clinically meaningful worsening in treatment-related symptoms such as diarrhea, peripheral neuropathy, constipation, dysphagia, appetite loss, and nausea/vomiting.
Lead author Maurice Pérol, MD, medical oncologist, Centre Léon Bérard, Lyon, France, said, “The patient-reported outcome data is consistent with the main results of the study. The primary analysis showed a similar response rate for crizotinib and alectinib, but a longer duration of response with alectinib. This is consistent with the improvements in health-related quality of life and lung cancer symptoms, which were of similar magnitude in both groups but lasted longer with alectinib.”
“The high level of CNS activity shown with alectinib in the primary analysis is consistent with the fact that fewer patients treated with alectinib reported clinically meaningful worsening in health-related quality of life or cognitive function compared to crizotinib,” he continued. “Finally, the superior tolerability profile of alectinib compared to crizotinib shown in this analysis is consistent with the adverse events profile recorded during the study.”
Dr. Pérol said: “The patient-reported outcome data supports the use of alectinib as a new standard of care in the frontline treatment of patients with ALK-positive lung cancer.”
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