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Novel ALK inhibitor effective for crizotinib-resistant NSCLC
Ceritinib, a selective anaplastic lymphoma kinase inhibitor, demonstrated high activity in patients with advanced, ALK-rearranged non–small cell lung cancer, according to results of a multicenter study.
The benefits of ceritinib (LDK-378, Novartis) extended to patients whose disease progressed during treatment with crizotinib (Xalkori, Pfizer), including those with and without resistance mutations in ALK, researchers wrote.
Alice Shaw
“Crizotinib has become a standard treatment agent for patients with advanced, ALK-rearranged NSCLC, but patients invariably develop resistance, leaving their treatment options limited,” researcher Alice Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center, said in a press release. “We found ceritinib to be highly effective in the majority of crizotinib-resistant patients, as well as those who had never received the drug, with mostly mild and manageable side effects.”
The dose-escalation phase of the study, conducted at centers in 11 countries, included 59 patients with advanced cancers that harbored genetic alterations in ALK.
Shaw and colleagues administered once-daily oral ceritinib in doses that ranged from 50 mg to 750 mg, with 750 proving to be the maximum tolerated dose. Dose-limiting toxicities included vomiting, diarrhea, elevated aminotransferase levels, dehydration and hypophosphatemia.
The subsequent expansion phase of the study — designed to evaluate antitumor activity, safety and pharmacokinetic properties of ceritinib — included 130 patients. Of these patients, 114 received at least 400 mg ceritinib daily. In that group, researchers reported a response rate of 58% (95% CI, 48-67) and a median PFS of 7 months (95% CI, 5.6-9.5)
Eighty patients in the study’s expansion phase had undergone prior treatment with crizotinib. Researchers reported a response rate of 56% (95% CI, 45-67) in that group. The investigators observed responses in patients who harbored resistance mutations in ALK, as well as in patients who did not have detectable mutations.
Disclosure: The researchers report funding from Be a Piece of the Solution, the Evan Spirito memorial Foundation, the NCI, Novartis Pharmaceuticals and the V Foundation.