Alectinib Meets DFS End Point in ALK+ Early-Stage NSCLC

Adjuvant treatment with alectinib (Alecensa) generated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared with platinum-based chemotherapy in patients with completely resected stage IB to IIIA, ALK-positive non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 ALINA trial (NCT03456076).¹

At the time of a prespecified interim analysis, overall survival (OS) data were immature. Regarding safety, no unexpected findings were noted.

Data from ALINA will be presented at an upcoming medical meeting and submitted to global health authorities, including the FDA and European Medicines Agency.

“[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 of Genentech, stated in a news release. “If approved, [alectinib] has the potential to treat [patients with] 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.”

In November 2017, the FDA approved alectinib for the frontline treatment of patients with ALK-positive, metastatic NSCLC.²

The randomized, active-controlled, multicenter, open-label ALINA study evaluated the efficacy and safety of adjuvant alectinib vs platinum-based chemotherapy in patients at least 18 years of age with completely resected stage IB (tumor ≥4 cm) to IIIA (T2-3 N0, T1-3 N1, T1-3 N2, T4 N0-1) NSCLC.3 Patients needed to have documented ALK-positive disease according to an FDA-approved and CE-marked test, be eligible for a platinum-based chemotherapy regimen, have an ECOG performance status of 0 or 1, and have adequate hematologic and renal function.

Key exclusion criteria included prior adjuvant radiotherapy for NSCLC, prior exposure to systemic anticancer therapy and ALK inhibitors, and stage IIIA N2 disease that should receive post-operative radiotherapy treatment in the opinion of the investigator.

During the study, 257 patients were randomly assigned to received 600 mg of oral alectinib twice per day for up to 24 months or until recurrence, unacceptable toxicity, withdrawal of consent, or death; or up to 4, 21-day cycles of platinum-based chemotherapy consisting of 75 mg/m2 of cisplatin on day 1, 25 mg/m2 of vinorelbine on days 1 and 8, 1250 mg/m2 of gemcitabine on days 1 and 8, and 500 mg/m2 of pemetrexed (Alimta) on day 1. Notably, carboplatin could be used for patients who experienced unacceptable toxicity with cisplatin.

Along with the primary end point of investigator-assessed DFS, secondary end points included OS, plasma concentration of alectinib and alectinib metabolite, and safety.

References

1. Genentech’s Alecensa delivers unprecedented phase III results for people with ALK-positive early-stage lung cancer. News release. Genentech. September 1, 2023. Accessed September 1, 2023. https://www.gene.com/media/press-releases/14999/2023-08-31/genentechs-alecensa
2. Alectinib approved for (ALK) positive metastatic non-small cell lung cancer (NSCLC). News release. FDA. November 6, 2017. Accessed September 1, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/alectinib-approved-alk-positive-metastatic-non-small-cell-lung-cancer
3. A study comparing adjuvant alectinib versus adjuvant platinum-based chemotherapy in patients with ALK positive non-small cell lung cancer. ClinicalTrials.gov. Updated August 23, 2023. Accessed September 1, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03456076