Alectinib Improves DFS Vs Chemo in ALK+ Non–Small Cell Lung Cancer

Investigators of the multi-center, open-label, randomized phase 3 ALINA study evaluated the safety and efficacy of alectinib vs chemotherapy in patients with completely resected stage IB to IIIA ALK-positive NSCLC

Adjuvant treatment with alectinib (Alecensa) produced a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared with platinum-based chemotherapy in patients with resected, early-stage, ALK-positive non–small cell lung cancer (NSCLC), according to a press release from Genentech on the phase 3 ALINA study (NCT03456076).

This improvement in DFS met the trial’s primary end point. Investigators reported that the overall survival (OS) data were not mature at the time of prespecified interim analysis of the trial. Additionally, treatment with alectinib did not produce any unexpected safety signals.

According to the press release, alectinib is the first ALK inhibitor to reduce the risk of death or disease recurrence for patients with ALK-positive NSCLC in a phase 3 clinical trial. Developers intend to share results from the ALINA trial at a future medical meeting and discuss their findings with the FDA, the European Medicines Agency, and other regulatory bodies across the world.

“[Alectinib] has transformed outcomes for people with advanced ALK-positive NSCLC, and now these strong results provide evidence for the first time that this medicine could also play a pivotal role in early-stage disease where there is significant unmet need,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in the press release. “If approved, [alectinib] has the potential to treat cancer before it has spread in a setting where treatment can increase the chances of cure, which is our ultimate goal at Genentech. We look forward to sharing these data with regulatory authorities in hopes of bringing this to patients as quickly as possible.”

Investigators of the multi-center, open-label, randomized phase 3 ALINA study evaluated the safety and efficacy of alectinib vs chemotherapy in patients with completely resected stage IB to IIIA ALK-positive NSCLC. A population of 257 patients were randomly assigned to receive 600 mg of alectinib twice a day or platinum-based chemotherapy. Treatment options in the comparator arm included cisplatin at 75 mg/m² intravenously every 21 days, vinorelbine at 25 mg/m² on days 1 and 8 every 21 days, gemcitabine at 1250 mg/m² on days 1 and 8 every 21 days, pemetrexed at 500 mg/m² every 21 days, or carboplatin.

The trial’s secondary end points included OS, plasma concentration of alectinib, and adverse effects.

Patients 18 years and older with documented ALK-positive disease based on an FDA-approved test and an ECOG performance status of 0 or 1 were able to enroll on the trial. Additional eligibility criteria included having adequate hematologic and renal function, being eligible to receive platinum-based chemotherapy in accordance with local labels or guidelines, and willingness to comply with scheduled visits and other study procedures.

Those who received prior adjuvant radiotherapy for NSCLC or prior exposure to systemic anti-cancer treatment and ALK inhibitors were not able to enroll on the trial. Patients were also unsuitable for enrollment if they had known sensitivity to any study drug components, malignancies outside of NSCLC within 5 years of study entry, any gastrointestinal disorder that may impact the ability to receive oral medication, or symptomatic bradycardia. Having a history of organ transplant or any psychological, sociological, or geographical condition that may impact the ability to comply with study protocol requirements was also grounds for exclusion from the trial.

Reference

Genentech’s Alecensa delivers unprecedented phase III results for people with ALK-positive early-stage lung cancer. News release. Genentech. August 31, 2023. Accessed September 1, 2023. https://shorturl.at/dhCP8