Alectinib Outpaces Crizotinib In Treatment of ALK+ NSCLC Patients in Phase 3 ALEX Trial

Researchers release updated data from the phase 3 ALEX trial comparing alectinib with crizotinib as first-line treatment against ALK-positive non-small cell lung cancer.

At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers announced updated results from the phase 3 ALEX trial which compared alectinib with crizotinib for the treatment of those with ALK-positive non-small cell lung cancer (NSCLC).

The results reveal that 152 patients treated with alectinib showed a median progression-free survival (PFS) of 34.8 months compared with just 10.9 months in the 151 patients who were treated with crizotinib.

“Think of it like a horse race, only it’s not about who crosses the finish line first, but how far the horses can run,” first author of the trial D. Ross Camidge, MD, PhD, the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, and director of Thoracic Oncology at the CU School of Medicine, said in a recent statement.

“In this trial, it’s as if half of the people ‘riding’ crizotinib had exhausted their horses at about 11 months. For patients on alectinib, when this trial first started reporting data last year, more than half were still on their horses still running,” he added. “Now, enough time has elapsed to estimate the median performance of these alectinib ‘horses’ more accurately.”

Alectinib (Alecensa) received approval by the US Food and Drug Administration (FDA) in December 2015 for patients with metastatic NSCLC with mutations in the ALK gene. In NSCLC patients, about 7% of tumors have rearrangements in the ALK gene. The ability of alectinib to shrink brain metastases “is an important effect for clinicians to understand,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a past statement.

The researchers found that at 10.9 months, half of the cancers that had been treated with crizotinib began to restart their growth; for the patients on alectinib, it took 34.8 months to reach the same “median PFS.”

“When preliminary data were reported last year, estimates were looking to be more like 25 months PFS on alectinib, so this jump to 34.8 months is huge and may surprise people,” Dr Camidge shared. “In reality, it’s just the patients’ progression tends to be rather sparse around the time of the 50% point, and when that happens the median can jump around a lot.”

The researchers also report that compared with just 12% of patients who received alectinib, 45% of those who were given crizotinib ended up developing brain metastases during the trial. Additional findings further suggested just how alectinib is “outpacing” crizotinib. For one, alectinib boasted an 82.9% overall response rate, while the rate for crizotinib proved to be 75.5%. Furthermore, those who received crizotinib experienced more side effects than those who received alectinib.

When it comes to the drugs hazard ratios, the researchers found that risk of progression or death for those on alectinib was just 43% that of those who received crizotinib.

The updated data further support alectinib as the standard-of-care for first-line treatment of ALK+ NSCLC, Dr Camidge said.

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