Alectinib trumps crizotinib in sustaining symptom improvements in ALK+ NSCLC
The next-generation TKI* alectinib maintains improvement in lung cancer symptoms for a longer duration than crizotinib, the current standard of care for patients with ALK-positive non-small–cell lung cancer (NSCLC), according to new data from the ALEX** study presented at ELCC 2018.
The primary analysis from ALEX showed significantly longer progression-free survival and lower toxicity with alectinib than with crizotinib in previously untreated patients with advanced ALK-positive NSCLC, which was presented in the ASCO 2017 Annual Meeting and published simultaneously in a medical journal. [N Engl J Med 2017;377:829-838]
“The patient-reported outcome [PRO] 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 [HRQoL] and lung cancer symptoms, which were of similar magnitude in both groups but lasted longer with alectinib,” said lead author Dr Maurice Pérol of the Centre Léon Bérard in Lyon, France.
Lung cancer-related symptoms, as assessed using the EORTC QLQ-LC13 questionnaire, improved to a clinically meaningful level (defined as ≥10-point change from baseline) in both treatment arms, but the duration of improvement with alectinib was longer compared with crizotinib (96 vs 84 weeks for cough, 96 vs 80 weeks for chest pain, 96 vs 68 weeks for fatigue, and 96 vs 68 weeks for pain in other parts). [ELCC 2018, abstract 138PD_PR]
Clinically meaningful improvement in HRQoL, based on the EORTC QLQ-C30 questionnaire, was also maintained for a longer duration with alectinib than with crizotinib (88 vs 68 weeks), although improvements were seen in both treatment groups.
Among the patients with baseline CNS metastases, fewer alectinib-treated patients had worsening HRQoL compared with those receiving crizotinib at week 4 (10.8 percent vs 20.6 percent), and the difference persisted through week 84 for most assessments (0 percent vs 16.7 percent). Furthermore, fewer patients in the alectinib arm reported worsening cognitive function compared with the crizotinib arm (17.9 percent vs 34.6 percent at week 32).
Clinically meaningful worsening of treatment-related symptoms such as constipation, diarrhoea, peripheral neuropathy, dysphagia, nausea/vomiting, and appetite loss were reported by fewer patients in the alectinib arm vs the crizotinib arm.
“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 HRQoL or cognitive function compared to crizotinib,” said Pérol. “[Also,] the superior tolerability profile of alectinib compared to crizotinib shown in this analysis is consistent with the adverse events profile recorded during the study.”
Alectinib as standard of care
“The ALEX trial was a practice-changing study that firmly placed alectinib as a first-line palliative treatment for ALK-positive NSCLC patients. This secondary analysis strengthens the rationale for alectinib as the standard of care in first-line treatment,” said invited discussant Dr Fiona Blackhall of The Christie NHS Foundation Trust, Manchester, UK.
As conducting clinical trials is costly, PROs are often not measured, according to Blackhall.
“In this context of palliating advanced lung cancer, living better is as important, if arguably not more important, than living longer. And for this reason, PROs and HRQoL are crucial to assess and analyse,” she continued. “In patients with advanced lung cancer the symptom burden is high, particularly cough, breathlessness and chest pain. And so to have meaningful palliation and improvement in symptoms is of paramount importance.”
“So alongside wishing to identify drugs that improve progression-free survival and overall survival ultimately, we need to ensure that those drugs also allow patients to live better. Goals of care are important in the everyday management of patients with lung cancer and alleviating the symptoms it causes is a key goal.”