This article is more than 5 years old. Information may no longer be current.
Crizotinib superior to chemotherapy for intracranial control in ALK-positive NSCLC
Click Here to Manage Email Alerts
First-line crizotinib provided better intracranial disease control than chemotherapy for patients with advanced ALK-positive non–small cell lung cancer who had treated brain metastases, according to results of the phase 3 PROFILE 1014 study.
Results from the international, multicenter, randomized, open-label study previously showed crizotinib (Xalkori, Pfizer) improved PFS, objective response rate and patient-reported outcomes compared with pemetrexed–platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. However, brain metastases are common in patients with lung cancer, causing significant morbidity and mortality.
“At the time of diagnosis, brain metastases are present in 23% to 31% of patients with ALK-rearranged NSCLC,” Benjamin J. Solomon, MBBS, PhD, FRACP, associate professor and head of the molecular therapeutics and biomarkers laboratory at Peter MacCallum Cancer Centre in Australia, and colleagues wrote. “Moreover, as patients live longer with increasingly effective targeted systemic therapies, the proportion of patients with brain metastases increases, such that up to 50% of patients alive at 2 years with EGFR-mutated or ALK-rearranged lung cancer will have brain metastases.”
Solomon and colleagues prospectively evaluated the intracranial efficacy of first-line crizotinib compared with pemetrexed–platinum chemotherapy in patients with advanced ALK-positive NSCLC.
The analysis included 343 patients, 73 of whom (23%) had stable treated brain metastases at baseline. Researchers randomly assigned patients 1:1 to 250 mg oral crizotinib twice daily or IV chemotherapy.
Results showed improvements in intracranial time to progression with crizotinib in the intent-to-treat population (HR = 0.6; 95% CI, 0.34-1.05), those with treated brain metastases (HR = 0.45; 95% CI, 0.19-1.07) and those without brain metastases at baseline (HR = 0.69; 95% CI, 0.33-1.45). However, these improvements did not reach statistical significance.
Among patients with treated brain metastases at baseline, crizotinib conferred significantly higher intracranial disease control rates than chemotherapy at 12 weeks (85% vs. 45%) and 24 weeks (56% vs. 25%).
Crizotinib improved PFS among patients with treated brain metastases (median, 9 months vs. 4 months; HR = 0.4; 95% CI, 0.23-0.69), those without brain metastases at baseline (11.1 months vs. 7.2 months; HR = 0.51; 95% CI, 0.38-0.69) and the intent-to-treat population (10.9 months vs. 7 months; HR = 0.45; 95% CI, 0.35-0.6).
Researchers observed higher ORRs with crizotinib among patients with treated brain metastases (77% vs. 28%) and those without brain metastases at baseline (74% vs. 50%).
Progressive disease occurred less frequently with crizotinib than chemotherapy in the intent-to-treat population (52% vs. 77%), patients with treated brain metastases (54% vs. 75%) and those without brain metastases at baseline (52% vs. 78%).
The researchers acknowledged several potential study limitations, including lack of details regarding prior radiotherapy, different schedules for brain imaging of patients with and without brain metastases at baseline, and lack of standard endpoints for evaluating intracranial efficacy.
“Management of central nervous system disease still remains a significant clinical challenge,” Solomon and colleagues wrote. “Effective therapies with central nervous system activity are needed, and future clinical trials of targeted therapies should appropriately evaluate patients with brain metastases, including those with untreated or unstable brain metastases, and incorporate prospective assessments of central nervous system efficacy.”– by Kristie L. Kahl
Disclosure: Solomon reports honoraria from AstraZeneca and Bristol-Myers Squibb; consultant roles with AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, Merck Sharp & Dohme, and Pfizer; research funding from Pfizer; royalties from VeriStrat; and travel accommodations from AstraZeneca, Bristol-Myers Squibb, Merck and Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts