Alectinib Approved by EC for ALK+ NSCLC
Jason M. Broderick
Published Online:1:39 PM, Wed March 1, 2017
Sandra Horning, MD
The approval, which follows a positive opinion from the Committee for Medicinal Products for Human Use, is based on data from 2 phase II trials. In the first study, labeled NP28761, the overall response rate (ORR) with alectinib was 52.2% (95% CI, 39.7%-64.6%) and the median progression-free survival (PFS) was 8.2 months (95% CI, 6.3-12.6).1 For the second trial, known as NP28673, the ORR was 50.8% (95% CI, 41.6%-59.9%) and the median PFS was 8.9 months (95% CI, 5.6-12.8).2
“Every year, an estimated 75,000 people are diagnosed with ALK-positive NSCLC worldwide,” Sandra Horning, MD, chief medical officer and head of global product development at Roche, said in a statement. “Development of resistance to the current standard of care underlines the need for alternative treatments. Today’s approval provides the promise of a new treatment option for people in Europe with this devastating disease.”
NP28761 was an open-label, single-arm multicenter trial that included 87 patients with ALK-positive NSCLC who progressed on crizotinib. In this study, which was conducted in North America, patients received alectinib at 600 mg orally twice daily until progression.
The median duration of response in the study was 14.9 months (95% CI, 6.9-NE) and the safety profile was consistent with previous trials.
The most common grade ≥3 adverse events (AEs) were an increase in blood levels of creatine phosphokinase (8%), increased ALT (6%), increased AST (5%), dyspnoea (3%), hypertriglyceridaemia (3%), hypokalaemia (3%), hypophosphatemia (3%), and thromboplastin (2%).
In the NP28673 study, crizotinib-pretreated patients received alectinib at 600 mg orally twice daily until progression. One hundred thirty-eight patients were evaluable for response. The median age of patients was 51.6 years and 60% had baseline CNS metastases. Most patients (80%) received prior chemotherapy.
The median duration of response in the trial was 15.2 months (95% CI, 11.2-24.9) and the safety profile was in line with prior studies of the drug. The most common grade ≥3 AE was dyspnoea (4%).
A pooled analysis of the 2 studies was conducted for patients with CNS metastases. The ORR in these patients was 64% (95% CI, 49.2%-77.1%). The complete response rate was 22% and the median duration of response in these patients was 11.1 months (95% CI, 7.6-NE).
According to Roche, the approval is conditional and requires that the company provide additional data from the ongoing phase III ALEX study (NCT02075840), which is comparing alectinib with crizotinib in the first-line setting for patients with ALK-positive NSCLC. Data from the trial are expected to be reported in the first half of this year.
- Gandhi L, Shaw AT, Gadgeel SM, et al. A phase II, open-label, multicenter study of the ALK inhibitor alectinib in an ALK+ non-small-cell lung cancer (NSCLC) U.S./Canadian population who had progressed on crizotinib (NP28761). J Clin Oncol. 2015;33 (suppl; abstr 8019).
- Ou S-HI, Ahn JS, Petris LD, et al. Alectinib in Crizotinib-Refractory ALK-Rearranged Non—Small-Cell Lung Cancer: A Phase II Global Study [Published online November 23, 2015]. J Clin Oncol. doi:10.1200/JCO.2015.63.9443.