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Benefit of first-line alectinib persists over crizotinib for ALK-positive lung cancer
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CHICAGO — Alectinib significantly prolonged PFS compared with crizotinib as first-line treatment for patients with ALK-positive non-small cell lung cancer, according to updated findings from the ALEX study presented at the ASCO Annual Meeting.
Primary analysis from the trial showed improved investigator-assessed PFS with alectinib (Alecensa, Genentech) compared with crizotinib (Xalkori, Pfizer; median, not reached vs. 11.1 months; HR 0.47, 95% CI 0.34-0.65).
“The primary endpoint of the ALEX study — which compared the only other licensed first-line ALK inhibitor, crizotinib, with the next-generation ALK inhibitor alectinib — was investigator-assessed PFS,” D. Ross Camidge, MD, PhD, professor of medical oncology and Joyce Zeff Chair in lung cancer research at University of Colorado, told HemOnc Today. “In 2017, the median PFS was not reached and the HR was 0.47. Now, with over 20 months of follow-up, the data are much more mature with a median PFS now estimable at 34.8 months and a further improvement in the HR to 0.43.”
Camidge and colleagues presented findings for an additional 10 months of follow-up from the dataset published in 2017. Eligible participants had stage IIIB/IV ALK-positive NSCLC, with no experience with systemic therapy for advanced disease. The researchers also allowed inclusion of patients with asymptomatic central nervous system metastases.
The analysis included 152 patients treated with 600 mg alectinib twice daily and 151 patients treated with 250 mg crizotinib twice daily.
For patients with CNS metastases, median PFS was 27.7 months in the alectinib arm and 7.4 months in the crizotinib arm (HR = 0.35; 95% CI, 0.22-0.56). Researchers observed a similar benefit for patients without CNS metastases, with a median PFS of 34.8 months for alectinib and 14.7 months for crizotinib (HR = 0.47; 95% CI, 0.32-0.71).
“The benefit is seen both for those with and without CNS metastases at baseline and really solidifies alectinib as the first-line ALK inhibitor of choice,” Camidge said.
Secondary endpoint findings showed an objective response rate of 82.9% (95% CI, 75.95-88.51) for alectinib compared with 75.5% (95% CI, 67.84-82.12) for crizotinib.
Median duration of response was 33.3 months in the alectinib arm and 11.1 months for crizotinib (stratified HR = 0.33; 95% CI, 0.23-0.48).
Camidge reported that OS data remain immature, with an event rate of 28.3% in the alectinib arm and 31.8% in the crizotinib arm (stratified HR 0.76, 95% CI 0.5-1.15).
Alectinib yielded lower rates of grade 3 to grade 5 adverse events than crizotinib (44.7% vs 51%), despite longer treatment duration (27 months vs. 10.8 months). Events leading to dose reductions also occurred less frequently with alectinib arm (16.4% vs 20.5%), as did dose interruptions (22.4% vs 25.2%). Discontinuation due to adverse events occurred among 13.2% of patients in both groups.
“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,” Camidge said in a press release. “In reality, it’s just that patients’ progression tends to be rather sparse around the time of the 50-percent point, and when that happens the median can jump around a lot.” – by Rob Volansky
Reference:
Camidge DR, et al. Abstract 9043. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Camidge reports honoraria from AstraZeneca, Bio-Thera, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana, Revolution Medicines, Roche, and Takeda, and receiving research funding from Takeda. Please see the abstract for all other author’s relevant financial disclosures.