Alectinib Improves PFS in Phase III ALK+ NSCLC Trial

Sandra Horning, MD

Sandra Horning, MD

Alectinib (Alecensa) significantly improved progression-free survival (PFS) compared with chemotherapy in patients with ALK-positive non—small cell lung cancer (NSCLC) who had progressed following treatment with platinum-based chemotherapy and crizotinib (Xalkori), according to findings from the phase III ALUR trial.

The randomized, open-label trial included 119 patients across 15 countries. Roche, the the developer of the second-generation ALK inhibitor alectinib, reported that the full study data will be published in a peer-reviewed publication later this year.

“We are pleased to announce that the results of the phase III ALUR trial further support the use of Alecensa as a treatment for people with ALK-positive lung cancer who, after having progressed on both chemotherapy and crizotinib, are in need of new treatment options,” Sandra Horning, MD, chief medical officer and head of global product development at Roche, said in a statement. “The results of this trial will support our access discussions with global health authorities as we seek to bring Alecensa to patients faster.”

The ALUR trial (NCT02604342) randomized patients with ALK-positive NSCLC in a 2:1 ratio to alectinib or platinum-based chemotherapy (pemetrexed or docetaxel). Patients had received 1 prior line of platinum-based chemotherapy and crizotinib. The primary endpoint was PFS, with secondary endpoints including overall survival, median time to CNS progression, and objective response rate (ORR) in patients with measurable brain metastases at baseline.

The FDA approved alectinib in December 2015 as a treatment for patients with metastatic ALK-positive NSCLC following progression on crizotinib, based on findings from 2 phase II clinical trials.

In the first study, labeled NP28761, the ORR with alectinib was 52.2% (95% CI, 39.7%-64.6%) and the median 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

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).

Alectinib is also being evaluated in the ongoing phase III ALEX study (NCT02075840), which is comparing the agent 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.

References

1. 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).
2. 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.