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Alectinib Highly Active in Crizotinib-Refractory ALK-Rearranged NSCLC

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Key Points

  • The objective response rate to alectinib was 50% in patients with crizotinib-refractory ALK-positive NSCLC.
  • The CNS disease control rate with alectinib was 83%.

In a phase II trial reported in the Journal of Clinical Oncology, Ou et al found that the investigational ALK inhibitor alectinib, which is active against acquired crizotinib (Xalkori) resistance mutations and exhibits high CNS penetration, was associated with considerable activity in patients with crizotinib-refractory ALK-positive non–small cell lung cancer (NSCLC).

Study Details

In the study, 138 patients were treated with oral alectinib at 600 mg twice daily. Of these patients, 61% had CNS metastases. The primary endpoint was objective response rate on central independent review committee assessment.

Response Rate

Overall, 122 patients were evaluable for response. These patients had a median age of 52 years, 56% were female, 66% were white, and 60% had central nervous system (CNS) metastases.

The objective response rate was 50% (95% confidence interval [CI] = 41%–59%), and the median duration of response was 11.2 months (95% CI = 9.6 months to not reached). In 96 patients (79%) who had previously received chemotherapy, the objective response rate was 45% (95% CI = 35%–55%). Median progression-free survival on independent review was 8.9 months (95% CI = 5.6–11.3 months) for all 138 patients.

CNS Response

Among 84 patients with baseline CNS metastases, 23 (27%) had a CNS complete response, and the overall CNS disease control rate was 83% (95% CI = 74%–91%). The CNS duration of response was 10.3 months (95% CI = 7.6–11.2 months). The CNS response rate in 35 patients with measurable CNS lesions was 57% (95% CI = 39%–74%; 7 with complete response).

Of 23 patients with measurable or nonmeasurable CNS metastases and no prior radiation, 10 (43%) had a complete CNS response. At 12 months, the cumulative CNS progression rate was 24.8%, and the cumulative non-CNS progression rate was 33.2% for all patients.

Adverse Events

Common adverse events were constipation (33%, all grade 1 or 2), fatigue (26%, 1% grade 3), and peripheral edema (25%, 1% grade 3). The most common grade 3 or 4 adverse event was dyspnea (3%, grade 3).

The investigators concluded: “Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases.”

The study was supported by F. Hoffmann-La Roche.

Sai-Hong Ignatius Ou, MD, PhD, of the University of California Irvine School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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