Expert discussion between Prof Emeritus Vansteenkiste and Prof Ingel Demedts: the ALINA trial

Experts: Prof Emeritus Johan Vansteenkiste (University Hospitals Leuven) and Prof Ingel Demedts (University Hospital Gent and DELTA Ziekenhuis Roeselare)

The ALINA trial was presented in the Presidential Session at ESMO 2023 by Prof Ben Solomon, focusing on adjuvant treatment options for patients with completely resected, ALK-translocated NSCLC. The main takeaway from the trial was the successful achievement of its primary endpoint.

In the ALINA trial, patients with stage IB to IIIA ALK+ NSCLC were randomized post-surgery to receive either adjuvant chemotherapy or alectinib for two years. The primary endpoint was PFS in stage II to III patients. Alectinib demonstrated a statistically significant improvement in PFS compared to chemotherapy, and this effect was confirmed in a secondary analysis for stage IB to stage IIIA patients.

One notable difference between ALINA and the ADAURA trial, which examined adjuvant osimertinib in EGFR-mutated NSCLC, was the duration of therapy. ADAURA used three years of osimertinib, while ALINA employed two years of alectinib. The rationale for this discrepancy lacks a strong scientific basis.

Additionally, the ALINA trial design differed from ADAURA in terms of patient recommendations for adjuvant chemotherapy. In contrast to the ADAURA trial, ALINA patients randomised to alectinib did not receive adjuvant pemetrexed, deviating from guidelines suggesting its use in these patients. This approach raised questions, as pemetrexed had previously shown benefit in ALK-translocated NSCLC.

Moving forward, the scientific community anticipates survival data from ALINA, which remains a crucial endpoint. While ADAURA has already shown survival benefits with osimertinib, ALINA’s data is not available yet. Trials exploring peri-operative settings are also underway, adding further depth to our understanding.

However, the discussion extends to whether conducting similar adjuvant trials for other oncogenic transformations, such as MET and RET, is feasible due to lower prevalence and rising costs. Regulatory agencies and reimbursement bodies will play a vital role in shaping the future of such studies.

In conclusion, the ALINA trial results present a significant advancement in the adjuvant treatment of ALK-translocated NSCLC. The emphasis is now on overall survival data, potential regulatory considerations, and the challenges of conducting similar trials for rare oncogenic subtypes.

Reference:

Ben Solomon – ALINA: efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC) – ESMO 2023 – LBA2