A new study has found that ceritinib (Novartis) was effective in treating non-small-cell lung cancer. The findings were published on March 27 in The New England Journal of Medicine by a research team headed by scientists at Massachusetts General Hospital in Boston Massachusetts.
Novartis targets an abnormality anomaly in a gene called anaplastic lymphoma kinase (ALK) gene, which plays a major role in about 5% of cases of non-small cell lung cancer (approximately 10,000 patients annually in the United States). The investigators note that non–small-cell lung cancer, which harbors the ALK gene is sensitive to the ALK inhibitor crizotinib; however, resistance invariably develops. Novartis is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies.
The researchers administered oral Novartis in doses of 50 to 750 mg once daily to patients with advanced cancers harboring ALK genetic abnormalities. In an expansion phase of the study, the subjects received the maximum tolerated dose. Patients were evaluated to determine the safety, pharmacokinetic properties, and antitumor activity of Novartis. (Pharmacokinetics describes how the body affects a specific drug after administration through the mechanisms of absorption and distribution, as well as the chemical changes of the substance in the body.) Tumor biopsies were performed before Novartis treatment to identify resistance mutations in ALK in a group of patients with non-small-cell lung cancer who had had disease progression during treatment with crizotinib.
The initial study group comprised of 59 patients were enrolled in the dose-escalation phase. The maximum tolerated dose of Novartis was 750 mg once daily; side-effects that limited dosage included diarrhea, vomiting, dehydration, elevated aminotransferase levels, and hypophosphatemia (low serum phosphorous). This phase was followed by an expansion phase. In this phase, an additional 71 patients were treated; thus, bringing the total study group to 130 patients overall. Among 114 patients who received at least 400 mg of Novartis per day, the overall response rate was 58%. Among 80 patients who had previously received crizotinib, the response rate was 56%. Responses were observed in patients with various types of resistance mutations in ALK and in patients without detectable mutations. Among the patients who received at least 400 mg of Novartis per day, the average progression-free survival was 7.0 months.
The authors concluded that Novartis was highly active in patients with this type of advanced cancer, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK.