Alectinib Maintains First-Line Therapy Status for ALK-Positive NSCLC

New York—For patients with non–small-cell lung cancer (NSCLC) and ALK mutation, first-line therapy with alectinib is standard care, however, sequence of therapy is not so readily defined.

At the 23rd Annual Perspectives in Thoracic Oncology meeting, Jessica J. Lin, MD, Attending Physician, Center for Thoracic Cancers, Massachusetts General Hospital, Boston, provided an overview of data regarding potential sequencing of therapies in patients with NSCLC and ALKmutation, and addressed the question of whether any other drugs could replace alectinib as being optimal for first-line care.

The ASCEND-4, ALEX, and ALTA-1L Clinical Trials

For the first-line treatment of patients with NSCLC and ALK mutation, use of alectinib is the standard of care. However, recent clinical trials have been conducted to determine whether crizotinib could function as the optimal first-line treatment option in this setting.

Dr Lin referred first to the ASCEND-4 clinical trial, which compared ceritinib (n = 189) with chemotherapy (n = 175) in patients with ALK-positive NSCLC.

“At the time of this clinical trial, crizotinib had not been globally approved as a first-line therapy,” she noted.

In ASCEND-4, the median progression-free survival was 16.6 months for patients who received ceritinib and 8.1 months for those who received chemotherapy, demonstrating the superiority of ceritinib over chemotherapy in terms of survival efficacy.

“The results were positive in favor of first-line ceritinib. However, this improved efficacy came at a cost of toxicity,” Dr Lin told attendees.

Rates for adverse events of all grades were higher with ceritinib than with chemotherapy, and included diarrhea, nausea, vomiting, and an increase in alanine aminotransferase.

“One would have to weigh the efficacy with the side effects that patients would have to struggle with,” she said.

Two other studies that Dr Lin highlighted were the global ALEX trial and the ALTA-1L trial, which compared alectinib (n = 152) versus crizotinib (n = 151) and brigatinib (n = 137) versus crizotinib (n = 138), respectively

In the ALEX study, alectinib reduced the risk for cancer growth or death by 53% compared with crizotinib.

In addition, in a subgroup analysis of patients with CNS metastases at baseline, alectinib extended the median time to progression by approximately 15 months. In addition, where 68 of patients in the crizotinib arm had events, only 18 had them in the alectinib arm.

In the ALTA-1L trial, the median progression-free survival was not reached in the brigatinib arm and was 9.2 months in the crizotinib arm.

“Brigatinib met the prespecified threshold for statistical superiority versus crizotinib,” she said.

Like ceritinib, brigatinib also led to many adverse events.

“In fact, 29% of patients who were treated with brig required dose reductions because of adverse events, 12 required drug discontinuation because of adverse events.

Study Results Underscore Alectinib’s Superiority 

When progression-free survival rates are compared between ceritinib, crizotinib, brigatinib, and alectinib, alectinib remains superior as a first-line therapy for patients with NSCLC and ALK mutation.

“I think this is why alectinib remains the standard of care for advanced ALK-positive NSCLC,” Dr Lin said.—Hina Khaliq