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Ceritinib effectively treats ALK–rearranged NSCLC
Ceritinib may safely and effectively treat patients with ALK–rearranged non–small cell lung cancer, including those with disease progression in the brain, according to results from the phase 2 ASCEND-2 trial.
Results of the ASCEND-1 trial showed ceritinib (Zykadia, Novartis) — a selective ALK oral inhibitor — induced robust antitumor efficacy in 163 patients with ALK–rearranged NSCLC, regardless of brain metastases status and prior therapy with an ALK protein inhibitor.
In the current analysis, Lucio Crinὸ, MD, of University Medical School of Perugia in Perugia, Italy, and colleagues evaluated ceritinib in 140 patients with ALK–rearranged NSCLC who were previously treated with at least one platinum-based chemotherapy and who experienced disease progression during treatment with crizotinib (Xalkori, Pfizer) as their most recent line of treatment. The cohort included those with asymptomatic or neurologically stable baseline brain metastases (71.4% of patients).
Patients received 750 mg oral ceritinib daily, for a median exposure of 8.8 months (range, 0.1-19.4).
Overall response rate served as the primary endpoint. Secondary endpoints included OS, safety and patient-reported outcomes.
Median follow-up was 11.3 months (range, 0.1-18.9).
The ORR in the overall population was 38.6% (95% CI, 30.5-47.2) and the disease control rate was 77.1% (95% CI, 69.3-83.8). Median time to response was 1.8 months (range, 1.6-5.6), and median duration of response was 9.7 months (95% CI, 7.1-11.1).
Median PFS in the population was 5.7 months (95% CI, 5.4-7.6) and median OS was 14.9 months (95% CI, 13.5 to not evaluable). The 12-month OS rate was 63.8% (95% CI, 54.9-71.4).
Researchers then conducted a subgroup analysis to evaluate outcomes in the 100 patients
with baseline brain metastases. The ORR in this cohort was 33% (95% CI, 23.9-43.1). Twenty patients had active target lesions at baseline, for whom the ORR was 45% (95% CI, 23.1-68.5).
“These data, together with emerging evidence for intracranial efficacy with other second-generation ALK inhibitors, suggest that patients who experience progression in the brain during crizotinib treatment may benefit from subsequent treatment with an alternative ALK–targeted therapeutic,” Crinὸ and colleagues wrote.
Adverse events reported in the phase 2 study were consistent with those reported in ASCEND-1. Gastrointestinal adverse events were the most prevalent — including nausea (81.4%), diarrhea (80%) and vomiting (62.9%). However, most adverse events were grade 1 or 2 and managed with dose interruption or reduction.
The researchers found patient compliance to be high. Patient-reported outcomes showed a trend toward no worsening cancer symptoms during treatment, improved symptom burden and a maintained global quality-of-life score.
“Considered together with results from ASCEND-1, these data are encouraging for heavily pretreated patients with advanced disease and high tumor burden, including those with disease progression in the brain,” Crinὸ and colleagues wrote. “These results support the positive benefit–risk profile of ceritinib compared with currently available therapies in patients with ALK–rearranged NSCLC who have experienced progression during crizotinib treatment.” – by Kristie L. Kahl
Disclosures: Crinὸ receives honoraria from and consultant/advisory roles with AstraZeneca, Eli Lilly, Novartis, Pfizer and Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures.