Episode 12: Alectinib massively improves DFS in early stage ALK+ NSCLC patients: the ALINA trial

In this episode of WND focusing on lung cancer, Prof Johan Vansteenkiste from University Hospitals Leuven and Prof Mariana Brandao, a medical oncologist at Institut Jules Bordet in Brussels, delve into the ALINA trial, which investigates the use of alectinib in patients with ALK+ NSCLC.

In the metastatic setting, ALK+ patients exhibit the best prognosis among NSCLC patients, with a median OS exceeding 5 years with the availability of third-generation TKIs. However, treatment options in the early setting are limited.

The phase 3 ALINA trial enrolled ALK+ NSCLC patients who had undergone surgery and randomly assigned them 1:1 to receive either placebo or alectinib treatment for 2 years at the maximum dose.

Results presented at ESMO2023 demonstrated a substantial increase in DFS, rising from 54% to 89%. This absolute benefit of 35% translates to one-third of patients who do not experience relapse or death due to this adjuvant therapy at 3 years, with an HR of 0.24 regardless of the disease stage.

The toxicity profile of alectinib differs from chemotherapy but is well-known in the metastatic setting, including liver alterations, significant weight gain, and hypertension. Careful monitoring and support are necessary to improve adherence to this therapy.

The CNS penetration of alectinib is a crucial aspect of treatment. In the ALINA trial, almost none of the patients receiving alectinib experienced progression in the brain, highlighting its relevance in the early setting of NSCLC.

The trial design excluded chemotherapy, a strategy deemed suboptimal by both experts in clinical practice. While targeted agents substantially delay relapse, the benefit of adjuvant chemotherapy is evident, as indicated by previous studies, despite the unknown proportion of ALK+ patients and in the context of the metastatic setting.

Patients should be informed, and if deemed fit for chemotherapy, it remains the preferred option. OS data are eagerly anticipated but may take time to gather due to the prolonged survival of patients on TKIs. Approval for reimbursement could be based on the remarkable DFS outcomes.