Alectinib Achieves 66.7% Major Pathological Response Rate in Neoadjuvant Treatment of Resectable ALK-Positive NSCLC: Interim Results from the NAUTIKA1 Trial Presented at WCLC 2023

Alectinib is a first-line treatment option for patients with advanced ALK-positive NSCLC. The ongoing Phase III ALINA trial (NCT03456076) is evaluating the efficacy of alectinib as adjuvant therapy. On September 1, 2023, Genentech announced that the interim analysis of the ALINA trial showed that adjuvant treatment with alectinib achieved the primary endpoint of DFS in patients with operable ALK-positive NSCLC at stages IB-IIIA, while OS data is not yet mature. However, the role of alectinib and other targeted therapies in the treatment of early-stage NSCLC remains unclear, particularly in the neoadjuvant setting.

NAUTIKA1 (NCT04302025) is an ongoing Phase II clinical trial designed to evaluate the efficacy and safety of neoadjuvant/adjuvant therapy in various resectable NSCLC with driver gene alterations.

According to previous reports, early analysis of Alectinib in the ALK cohort of the NAUTIKA1 study indicated good tolerability. During this year's WCLC, data on efficacy, surgical outcomes, and safety were presented, with a data cutoff date of July 31, 2023.

The study enrolled patients aged ≥18 years with resectable IB, II, IIIA, or selected IIIB stage ALK-positive NSCLC who received neoadjuvant treatment with alectinib 600 mg (twice daily) for 8 weeks followed by surgical treatment. The primary endpoint was the major pathological response (MPR) rate, and secondary endpoints included radiological response, pathological complete response (pCR), surgical outcomes, and safety.

As of the data cutoff date, a total of 12 patients were enrolled, with 9 eligible patients proceeding to the neoadjuvant treatment phase and being assessable for pathological response. The duration of neoadjuvant treatment with Alectinib was 8 weeks (7.9-8.7), and all patients received ≥2 cycles of Alectinib treatment. The baseline characteristics of the patients are shown in the figure below.

In terms of efficacy, the MPR was 66.7% (6/9), with 3 patients achieving pCR, 4 patients achieving partial response (PR), and 5 patients achieving stable disease (SD). No patients experienced disease progression during the neoadjuvant treatment. Regarding downstaging after treatment, 1 patient decreased from stage IIIB to stage IIIA, and 1 patient decreased from stage IIIA to stage IIB.

In terms of surgical outcomes, R0 resection was achieved in 8 patients, with no complications or injuries occurring during the major surgeries. Post-surgery, 8 patients received adjuvant therapy: 3 underwent chemotherapy plus alectinib, 4 were treated with alectinib alone, and 1 received chemotherapy alone. The median treatment duration for adjuvant alectinib was 56.6 weeks.

In terms of safety, there were no surgical delays or treatment interruptions due to AEs, no life-threatening AEs, and no serious AEs. Four patients reported treatment interruptions or dose reductions due to AEs, and most AEs were grade 1-2.

Existing data suggest that alectinib neoadjuvant therapy is associated with pathological response, well-tolerated treatment, and no surgery delays related to treatment; the study is ongoing with continued enrollment.

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