Alectinib improves lung cancer symptoms longer than crizotinib
Alectinib conferred longer symptom improvement than crizotinib among patients with ALK-positive non-small cell lung cancer, according to results of a phase 3 trial presented at the European Lung Cancer Congress.
Earlier results from the ALEX trial showed alectinib (Alecensa, Genentech) prolonged PFS and delayed time to CNS metastases compared with crizotinib (Xalkori, Pfizer). The current analysis evaluates patient-reported outcomes and health-related quality-of-life data.
“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,” Maurice Perol, MD, medical oncologist at Centre Leon Berard in France, said in a press release. “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 [with] crizotinib.
“Finally, the superior tolerability profile of alectinib compared [with] crizotinib shown in this analysis is consistent with the adverse events profile recorded during the study,” Perol added.
Researchers randomly assigned 303 patients with treatment-naive ALK-positive NSCLC 1:1 to receive 600 mg twice daily alectinib or 250 mg twice daily crizotinib.
PFS served as the main endpoint.
Researchers used EORTC QLQ/QLQ-LC13 questionnaires to collect patient-reported outcomes in health-related quality of life and lung cancer symptoms. Patients completed the questionnaires at baseline, every 4 weeks during treatment, within 4 weeks after study withdrawal and after disease progression.
Other endpoints included time to deterioration in symptoms and health-related quality of life and the proportion of patients who experienced clinically meaningful change from baseline.
Nearly two-thirds of patients in both groups completed questionnaires (alectinib, n = 100; 65.8%; crizotinib, n = 92; 64.2%).
Both arms had similar median time to deterioration in the composite symptoms endpoint that comprised chest pain, cough and dyspnea (HR = 1.1; 95% CI, 0.72-1.68).
Patients assigned alectinib reported a longer mean duration of clinically meaningful improvement in lung cancer symptoms from baseline compared with those assigned crizotinib for cough (week 96 vs. week 84), chest pain (week 96 vs. week 80), fatigue (week 96 vs. week 68) and pain in other parts of the body (week 96 vs. week 68).
Those in the alectinib group reported a longer duration of improvement in health-related quality of life than those in the crizotinib group (week 88 vs. week 68).
Among patients with CNS metastases, fewer patients assigned alectinib experienced worsening health-related quality of life starting at week 4 (10.8% vs. 20.6%). This difference persisted in subsequent assessments through week 84 (0% vs. 16.7%).
Fewer patients in the alectinib group with CNS metastases experienced worsening cognitive function at 32 weeks (17.9% vs. 34.6%).
Improvements also extended to treatment-related symptoms. Fewer patients assigned alectinib reported peripheral neuropathy, diarrhea, dysphagia, appetite loss, constipation, and nausea or vomiting.
“[Among] patients with advanced lung cancer the symptom burden is high, particularly cough, breathlessness and chest pain,” Fiona Blackhall, BSc, MBChB, FRCP, PhD, CCST, honorary consultant in medical oncology at Christie NHS Foundation Trust in the U.K., said in commentary accompanying the press release.
“Alectinib prolonged the improvement in those symptoms,” Blackhall added. “That fits in with the previously reported improvement in PFS and favorable tolerability with alectinib.” – by Andy Polhamus
Perol M, et al. Abstract 138PD. Presented at: European Lung Cancer Congress; April 12, 2018; Geneva.
Disclosures: Perol reports advisory roles with Pfizer and Roche. Please see the abstract for all other authors’ relevant financial disclosures. HemOnc Today could not confirm Blackhall’s relevant financial disclosures at the time of reporting.