ALINA Trial: Anticancer Activity of Alectinib Reported in Earlier-Stage, ALK-Positive NSCLC

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Treatment with the anaplastic lymphoma kinase (ALK) inhibitor alectinib significantly reduced the risk of recurrence or death by 76% (P < .0001) in patients with completely resected stage IB to IIIA ALK-positive non–small cell lung cancer (NSCLC) compared with platinum-based chemotherapy. This finding was from the primary analysis of the phase III ALINA trial presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2023.1

The results also showed a 78% improvement in central nervous system (CNS) disease–free survival for alectinib vs platinum-based chemotherapy. The safety and tolerability of alectinib in this trial were consistent with those in previous trials in the metastatic setting, and no unexpected safety findings emerged. Overall survival data are still immature.

Benjamin J. Solomon, MBBS, PhD

Benjamin J. Solomon, MBBS, PhD

“This improvement in disease-free survival is statistically significant and clinically meaningful. These potentially practice-changing data reinforce the potential of alectinib as a new standard of care in the ALK-positive early lung cancer setting, where treatment options are currently platinum-based chemotherapy,” said Professor Benjamin J. Solomon, MBBS, PhD, a medical oncologist at Peter MacCallum Cancer Centre, Australia. “The magnitude of disease-free survival observed in this study could represent a paradigm shift in the way we manage early-stage ALK-positive lung cancer. These results reinforce the importance of genetic testing,” he added.

ALK mutations or rearrangements occur in about 5% of all cases of NSCLC. These patients are generally younger (≤ 55 years), never smokers, and at increased risk for developing CNS metastases compared with other types of NSCLC. About 50% will develop brain metastases. Once the disease recurs after treatment, it is usually metastatic and considered incurable.

Alectinib is approved by the U.S. Food and Drug Administration for the treatment of ALK-positive NSCLC in the metastatic setting. The ALINA trial evaluated its use as a first-line therapy.

Study Details

ALINA is a phase III, randomized, active-controlled, multicenter, open-label trial evaluating the efficacy and safety of first-line adjuvant alectinib (600 mg/d for 2 years) compared with four cycles of platinum-based chemotherapy in patients with completely resected stage IB to IIIA ALK-positive NSCLC. The study randomly assigned 257 patients 1:1 to receive the investigational therapy or control treatment. Patients were stratified by stage of disease (II vs IIIA) as well as by race (Asian vs non-Asian).

The primary endpoint was disease-free survival. Secondary endpoints include overall survival and safety.

Baseline characteristics were balanced between the two arms. Most patients were never smokers who had undergone a lobectomy and had nonsquamous disease. Stage IIIA disease was present in about 54% of patients, and about 50% had node-positive disease at baseline.

Key Outcomes

At a median follow-up of 27.9 months, median disease-free survival was not yet reached with alectinib vs 44.4 months with chemotherapy. The 2-year disease-free survival rate was 93.8% vs 63%, respectively. The corresponding 3-year disease-free survival rate was 88.3% vs 53.3%, respectively.

In the intention-to-treat population (ie, the entire study population with stage IB–IIIA disease), the median disease-free survival was not reached in alectinib-treated patients vs 41.3 months for the chemotherapy arm, for a 76% improvement in disease-free survival (P < .0001). In the intention-to-treat population, the 2-year disease-free survival rate was 93.6% vs 63.7%, respectively, and the 3-year disease-free survival rate was 88.7% vs 54.0%, respectively.

“The disease-free survival benefit was seen consistently across subgroups, and improvement in CNS disease–free survival was observed,” Dr. Solomon said.

When analyzed outcomes according to disease stage, alectinib improved disease-free survival by 79% in stage IB, 76% in stage II, and 75% in stage IIIA disease.

Brain recurrences were reported in 4 patients in the alectinib arm vs 14 in the chemotherapy arm. The 2-year rate of CNS disease–free survival was 98.4% vs 85.8%, respectively; at 3 years, the rate was 95.5% vs 79.7%, respectively.

The incidence of grade 3 or 4 adverse events was comparable in both arms of the study: 30% with alectinib and 31% with chemotherapy. No Grade 5 events were observed in either treatment arm. Treatment discontinuations from adverse events were reported in 5.5% of the alectinib-treated patients vs 12.5% of the chemotherapy arm. Dose reductions because of adverse events were reported in 26% of the alectinib-treated group and 10% of the chemotherapy arm; dose interruptions from an adverse event occurred in 27% vs 18%, respectively.

Three other clinical trials are studying alectinib in stage I–III NSCLC: the phase II NAUTIKA1 trial and ALNEO trials, and the phase III HORIZON-01 trial. 

DISCLOSURE: Dr. Solomon has received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, and Roche/Genentech; has served as a consultant or advisor to Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Roche/Genentech, and Pfizer; and has received research funding from Sanofi.


1. Solomon BJ, Ahn JS, Dziadziuszko R, et al: Efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer. ESMO Congress 2023. Abstract LBA2. Presented October 21, 2023.

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Expert Point of View: Marina C. Garassino, MD

Formal discussant of the ALINA trial Marina C. Garassino, MD, of the University of Chicago, agreed these results are “impressive and practice changing.” However, she said, at this point, more consideration is needed before jettisoning chemotherapy.

Marina C. Garassino, MD

Marina C. Garassino, MD

“I don’t think we...