Alectinib Highly Effective in ALK-positive NSCLC

June 11, 2015

The next-generation ALK inhibitor alectinib has demonstrated robust objective response rates (ORR) in patients with ALK-positive non–small cell lung cancer, including those with central nervous system metastases.

Sai-Hong Ignatius Ou, MD, PhD

The next-generation ALK inhibitor alectinib has demonstrated robust objective response rates (ORR) in patients with ALK-positive non—small cell lung cancer (NSCLC), including those with central nervous system (CNS) metastases, according to two presentations at the 2015 ASCO Annual Meeting.

In the first study, the second-generation ALK inhibitor alectinib demonstrated activity in patients with ALK-positive NSCLC following progression on crizotinib (Xalkori), including those with CNS metastases. In data presented from the phase II trial, alectinib showed an ORR of 50%, with a duration of response of 11.2 months.

"Alectinib achieved a robust response rate in crizotinib-resistant patient populations, a majority of whom received a platinum-based chemotherapy," lead investigator Sai-Hong Ignatius Ou, MD, PhD, a health science associate clinical professor at the University of California, Irvine, said during his presentation. "The disease control rate in the CNS was excellent, with a sustained median duration of 10.3 months. These data taken together may signal a new standard of care for CNS metastases in ALK-positive non-small cell lung cancer."

The highly selective oral ALK inhibitor alectinib has potent clinical activity against many of the clinically relevant acquired resistance mutations that render crizotinib ineffective. This activity allows alectinib to be highly effective following crizotinib resistance. Additionally, alectinib has demonstrated activity in the CNS, which is a common site of progression for patients treated with crizotinib.

In the phase II study, 122 crizotinib-pretreated patients were evaluable for response. The median age of patients was 51.6 years and 60% had baseline central nervous system (CNS) metastases. Most patients (80%) had received prior chemotherapy.

The median progression-free survival (PFS) with alectinib was 8.9 months (95% CI, 5.6-11.3). The ORR in the full population of patients was 50%, which consisted of all partial responses (PR). The stable disease rate was 35%, for a total disease control rate of 96% (95% CI, 70.6-85.6).

In all patients enrolled in the study with CNS metastases, the CNS-specific ORR was 57.1%, with a complete response (CR) rate of 27.4%. In those with untreated CNS metastases, the CR rate was 43.5%.

Grade 3/4 adverse events were relatively infrequent. Dose reductions due to adverse events were required in 8.7% of patients. Dose delays or interruptions were needed in 19.6% of patients.

"More than 90% of patients were able to tolerate alectinib without dose reductions," Ou said.

In a second study being presented at the ASCO meeting, treatment with alectinib demonstrated an ORR of 47.8%.4 In patients with CNS metastases, the ORR was 68.8% in this study, with a median duration of response of 7.5 months.

Genentech, the company developing alectinib in the United States, plans to submit results from the two clinical trials presented at ASCO to the FDA for a potential approval for patients with ALK-positive NSCLC. Alectinib was approved in Japan for this indication last year, under the name Alecensa.

The phase III ALEX study is comparing alectinib with crizotinib in chemotherapy-naive patients with ALK-positive NSCLC. In this study, alectinib will be administered at 600 mg twice daily with food. The study hopes to enroll 286 patients, with early results expected in 2018.

  1. Ou IS-H, Ahn JS, Petris LD, et al. Efficacy and safety of the ALK inhibitor alectinib in ALK+ non-small-cell lung cancer (NSCLC) patients who have failed prior crizotinib: An open-label, single-arm, global phase 2 study (NP28673).J Clin Oncol. 2015;33 (suppl; abstr 8008).
  2. 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).