Safety Data Help Affirm Adjuvant Alectinib as a New SOC in ALK+ NSCLC

Safety findings from the phase 3 ALINA trial (NCT03456076) that evaluated adjuvant alectinib (Alecensa) compared with platinum-based chemotherapy in patients with ALK-positive non–small cell lung cancer (NSCLC) further confirm the TKI’s role as a new standard treatment for this patient population, according to Hidehito Horinouchi, MD, PhD.

These updated safety findings from the trial were presented at the 2024 IASLC World Conference on Lung Cancer, which compared adverse effects (AEs) experienced in patients with ALK-positive NSCLC in the alectinib (n = 128) and chemotherapy (n = 120) arms.1 Any-grade AEs were reported in 98% and 93% of patients in the respective arms. Grade 3 or 4 treatment-related AEs were observed in 18% and 28% of patients in the alectinib and chemotherapy arms, respectively.

In the alectinib arm, the rates of AEs leading to dose reductions, dose interruptions, and treatment withdrawal were 26%, 27%, and 5%, respectively. These respective rates were 10%, 18%, and 13% in the chemotherapy arm.

“Based on this safety profile in the ALINA trial, alectinib adjuvant treatment is one of the new standard treatment strategies for ALK-positive NSCLC after complete resection,” Horinouchi said in an interview with OncLive^®.

Prior data from ALINA supported the FDA approval of alectinib in April 2024 for use as adjuvant treatment following tumor resection in patients with ALK-positive NSCLC whose tumors are at least 4 cm or node positive, as detected by an FDA-approved test.²

In the interview, Horinouchi discussed the safety outcomes of adjuvant alectinib vs platinum-based chemotherapy in patients with ALK-positive NSCLC and the next steps for alectinib.

Horinouchi is a medical oncologist in the Department of Thoracic Oncology at the National Cancer Center Hospital in Tokyo, Japan.

OncLive: What was the rationale of the ALINA trial, and what data were previously presented?

Horinouchi: ALINA is the only clinical trial testing the adjuvant activity of alectinib, an ALKTKI, in direct comparison with platinum-doublet chemotherapy. This trial was finished and published in the last year at the 2023 ESMO Congress, and the result has been fantastic.

At the first presentation, the DFS HR was 0.24 [95% CI, 0.13-0.43; P < .0001]. Also, there was a better trend in the central nervous system DFS [favoring alectinib (HR; 0.22; 95% CI, 0.08-0.58)]. During the 2024 IASLC World Conference on Lung Cancer, my colleagues and I published the safety analysis of the ALINA trial.

What did you present regarding updated safety data?

Overall, the safety analysis result was consistent with the [data for alectinib] in the advanced disease setting. The most frequent AE was mainly laboratory abnormalities, including increased [levels of] blood creatine phosphokinase [CPK], aspartate aminotransferase, alanine aminotransferase, and blood bilirubin.

Based on such AEs, patients are not suffering from symptomatic AEs. When we focus on the most frequent laboratory abnormalities, the [increased levels of] CPK were the most common. However, the proportion of patients who experienced dose interruption or reduction was approximately 25% of the patients. On the other hand, discontinuation in this patient population [treated with alectinib] was only 5.5%; as a result, the median duration of treatment was 23.9 months, which was nearly the same as the planned protocol treatment duration.

What are the next steps and future directions with alectinib?

Is there any chance for the combination of [alectinib] and chemotherapy? ALINA was a direct comparison between the TKI and chemotherapy. Therefore, the discussant recommended we seek the option for the combination with the chemotherapy, like the [phase 3] FLAURA2 trial [(NCT04035486) of osimertinib (Tagrisso) with or without chemotherapy] in the advanced setting [for EGFR-mutated NSCLC].

However, based on the very scant population of [patients with] ALK-positive NSCLC, doing this kind of [combination] clinical trial is very tough in terms of gathering the patient population. Therefore, based on my consideration, in [the long-term] future, there is no other option other than alectinib in this field.

References

1. Horinouchi H, Solomon B, Wu YL, et al. ALINA safety results: adjuvant alectinib vs chemotherapy in patients with resected ALK+ non–small cell lung cancer (NSCLC). Presented at: 2024 IASLC World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract OA13.04.
2. FDA approves alectinib as adjuvant treatment for ALK-positive non-small cell lung cancer. FDA. April 18, 2024. Accessed October 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-alectinib-adjuvant-treatment-alk-positive-non-small-cell-lung-cancer