FDA Approves Alectinib for ALK-Positive, Metastatic Non–Small-Cell Lung Cancer

TON Web Exclusives - Lung Cancer

Alectinib (Alecensa), a highly selective ALK inhibitor, recently garnered FDA approval for the frontline treatment of patients with metastatic non–small-cell lung cancer (NSCLC) who have ALK mutations as identified by the FDA-approved VENTANA ALK (D5F3) CDx Assay.1 Previously approved in the same patient population for those whose disease progressed with, or were intolerant of, crizotinib (Xalkori), alectinib’s approval as a first-line therapy was based on results from the randomized, open-label, phase 3 ALEX trial, in which it showed greater efficacy than crizotinib, with fewer adverse events (AEs).1,2

“This is the first head-to-head trial to compare a next-generation ALK inhibitor with the standard of care, crizotinib,” said the study’s lead author, Alice T. Shaw, MD, PhD, Director of Thoracic Oncology at Massachusetts General Hospital Cancer Center, Boston, who presented the results at the 2017 ASCO Annual Meeting in Chicago, IL.3 “This global study establishes alectinib as the new standard of care for initial treatment in this setting.”

For the study, Dr Shaw and colleagues enrolled 303 patients with treatment-naïve, advanced ALK-positive NSCLC—including those with asymptomatic central nervous system (CNS) disease—and randomized them 1:1 to receive oral treatment with either 600 mg alectinib twice daily or 250 mg crizotinib twice daily.2,3

Meeting its primary end point of investigator-assessed prolonged progression-free survival (PFS), alectinib showed a significantly higher 12-month PFS rate than crizotinib, at 68.4% (95% confidence interval [CI], 61.0-75.9) compared with 48.7% (95% CI, 40.4-56.9), respectively.2 The secondary end point of independent review committee (IRC)-assessed PFS demonstrated similar results, at 25.7 months (95% CI, 19.9-not estimable) in patients treated with alectinib versus 10.4 months (95% CI, 7.7-14.6) with crizotinib.1

Additional secondary end points included time to CNS progression, objective response rate (ORR), and overall survival.1-3 Alectinib again showed superior efficacy, with significant improvement in IRC-assessed cause-specific CNS progression.1 Patients in the alectinib arm had a lower rate of CNS progression as the first site of disease progression, alone or with systemic progression (12% vs 45%).1 The confirmed ORR was 79% (95% CI, 72-85) in the alectinib arm and 72% (95% CI, 64-79) in the crizotinib arm.1

In the alectinib arm, 126 patients achieved a response, for a response rate of 82.9% (95% CI, 76.0-88.5). In the crizotinib arm, a response was observed in 114 patients, for a response rate of 75.5% (95% CI, 67.8-82.1).2

Grade 3 to grade 5 AEs occurred less frequently with alectinib than with crizotinib, at 41% versus 50%, respectively.2 The most common AEs occurring in ≥20% of patients treated with alectinib were fatigue, constipation, edema, myalgia, and anemia. Serious AEs were reported by 28% of patients in the alectinib arm. AEs that led to discontinuation of alectinib occurred in 11% of patients; of these, AEs that led to discontinuation in ≥1% of patients were renal impairment, hyperbilirubinemia, increased alanine aminotransferase, and increased aspartate aminotransferase. Dose interruptions due to AEs occurred in 19% of alectinib-treated patients, whereas dose reductions were required in 16% of patients.1

“Nobody expected it would be possible to delay advanced lung cancer progression by this much,” Dr Shaw said.3 “Most targeted therapies for lung cancer are associated with a median progression-free survival of roughly 12 months.”

1. US Food and Drug Administration. Alectinib approved for (ALK) positive metastatic non-small cell lung cancer (NSCLC). November 7, 2017. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm584082.htm. Accessed January 26, 2018.
2. Peters S, Camidge DR, Shaw AT, et al; for the ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer. N Engl J Med. 2017;377:829-838.
3. Goodman A. Alectinib vs crizotinib in first-line treatment of ALK-positive NSCLC. The ASCO Post. June 25, 2017. www.ascopost.com/issues/june-25-2017/alectinib-vs-crizotinib-
in-first-line-treatment-of-alk-positive-nsclc. Accessed January 26, 2018.

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Last modified: February 14, 2018

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