Neoadjuvant Alectinib Yields Responses in Late-Stage, Potentially Resectable ALK+ NSCLC

Alectinib in ALK+ NSCLC | Image Credit:

© Image by Ashling Wahner & MJH Life

Sciences Using AI

Treatment with neoadjuvant alectinib (Alecensa) generated major pathologic responses (MPRs), including pathologic complete responses (pCRs), in patients with potentially resectable, stage III, ALK-positive non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 2 ALNEO trial (NCT05015010).

Data from the final analysis of the trial, which were presented at the 2025 ASCO Annual Meeting, showed that MPR was achieved by 42% of patients (n = 14; 90% CI, 28%-58%), with pCRs seen in 12% of patients (n = 4; 95% CI, 3%-28%). Non-MPRs were seen in 40% (n = 13) of patients, and 18% of patients (n = 6) were not assessed. Furthermore, 5 patients did not undergo surgery, and 1 patient underwent explorative thoracotomy.

The overall response rate (ORR) was 67% (n = 22); 0% of patients experienced CRs, 67% of patients (n = 22) experienced partial responses (PRs), 30% of patients had stable disease, and 3% of patients had progressive disease (n = 1).

With a median follow-up of 20.3 months (IQR, 12.3-34.1), recurrence of disease was experienced by 18% of patients (n = 6), and 91% of patients (n = 30) remained alive. The median event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were all not reached.

“With the limitation of a small phase 2 nonrandomized trial, [the] ALNEO study suggests alectinib as an active and feasible perioperative option in patients with resectable, stage III, ALK-positive NSCLC,” wrote lead study author Marcello Tiseo, MD, PhD, with coauthors in the presentation.

Tiseo is a professor in the Department of Medicine and Surgery at the University of Parma and head of the Medical Oncology Unit at the University Hospital of Parma in Italy.

The trial enrolled a total of 33 patients who completed neoadjuvant treatment consisting of 600 mg of alectinib twice a day for 2 cycles, 28 of whom advanced to surgery, and 26 of whom advanced to adjuvant treatment with 600 mg of alectinib twice a day for 24 cycles. Eligible patients had resectable, locally advanced, stage III NSCLC, were candidates for surgical resection after multidisciplinary discussion, had ALK-positive disease, had received no prior treatment, and had an ECOG performance status of 0 or 1.

The median age of patients was 62 years (IQR, 49-74). Among the 33 enrolled patients, 70% were female, 52% were nonsmokers, 76% had an ECOG performance status of 0, 97% had adenocarcinoma histology, 79% had a histological diagnosis, and 52% had an immunohistochemistry ALK evaluation. Additionally, stage IIA disease was present in 64% of patients, 31% of patients had T3 stage disease, and 82% of patients had N2 stage disease. It was noted that the most represented stages were T3N2 (24%), T2aN2 (15%), T4N0 (12%), and T4N2 (12%).

The trial’s primary end point was MPR, defined as the presence of 10% or less of viable tumor, by blinded independent central review (BICR). The secondary end points were pCR by BICR, ORR, EFS, DFS, OS, and safety. An ancillary biological study for the correlation of tissue and cell-free biomarkers with MPR and DFS is ongoing; tissue was collected at diagnosis and surgery; plasma was collected at baseline, after 4 and 8 weeks of neoadjuvant therapy, within 2 weeks of surgery, and at the time of recurrence.

Regarding surgery and downstaging, 85% of patients (n = 28) underwent surgery, and 86% of patients (n = 24) had R0 resection. Types of surgery included lobectomy in 64%, pneumonectomy in 9%, and other in 12% of patients. Adjuvant alectinib was administered to 79% of patients, with a median of 5.1 weeks (IQR, 3.6-6.0) from surgery and a median of 14 cycles (range, 1-25). Additionally, 48% (n = 13/27) of patients had nodal downstaging.

In the neoadjuvant phase (n = 33), any treatment-related adverse effects (TRAEs) were experienced by 100% of patients, and 9% of patients had grade 3 TRAEs; TRAEs led to dose reduction and treatment discontinuation in 6% and 0% of patients, respectively. Treatment-emergent AEs (TEAEs) included increased alanine aminotransferase (ALT) levels (grade 1/2, 12%; grade 3, 3%), increased aspartate aminotransferase levels (15%; 0%), asthenia (15%; 0%), and diarrhea (3%; 3%).

In the adjuvant phase, any TRAE was experienced by 100% of patients, and grade 3 TRAEs were experienced by 12% of patients; TRAEs led to dose reduction and treatment discontinuation in 27% and 4% of patients, respectively. TEAEs included asthenia (grade 1/2, 23%; grade 3, 0%), increased bilirubin levels (23%; 0%), increased ALT levels (15%; 4%), and neutropenia (0%; 4%).

No grade 4/5 or treatment-related serious AEs were observed in the neoadjuvant or adjuvant phases.

Reference

Leonetti A, Boni L, Gnetti L, et al. Alectinib as neoadjuvant treatment in potentially resectable stage III ALK-positive NSCLC: final analysis of ALNEO phase II trial (GOIRC-01-2020-ML42316). J Clin Oncol. 2025;43(suppl 16):8015. doi:10.1200/JCO.2025.43.16_suppl.8015