Around 30-40% of NSCLC patients receive a diagnosis of resectable disease. Despite undergoing treatment, there remains a significant risk of the disease recurring. Anaplastic lymphoma kinase (ALK) rearrangements are identified in approximately 4-5% of NSCLC cases. In 2015, accelerated approval was granted for ALECENSA (alectinib) to address ALK-positive metastatic NSCLC in patients who either experienced progression or could not tolerate XALKORI (crizotinib). Presently, the company's primary focus is on early-stage ALK-positive NSCLC, with Phase III trial results presented at ESMO 2023.

The ALINA study is a Phase III, randomized, active-controlled, multicenter, open-label study evaluating the efficacy and safety of adjuvant alectinib compared with platinum-based chemotherapy in people with completely resected Stage IB to IIIA ALK-positive NSCLC.

A total of 257 patients were randomized to receive alectinib (n=130) or chemotherapy (n=127); baseline characteristics were overall well-balanced between arms. At the data cutoff on 26 June 2023, the median follow-up was 27.8 months. A significant disease-free survival (DFS) benefit was observed with alectinib versus chemotherapy in both the stage II–IIIA and intention-to-treat (ITT) populations. A clinically meaningful CNS-DFS benefit was observed in the ITT population. OS data was immature. No unexpected safety findings were observed. As per the analysis, after three years, approximately 88.7% of patients who used ALECENSA were still alive without experiencing disease recurrence. In contrast, those in the chemotherapy group had a survival rate of 54%.

KOL insights

“Practice changing trial ALINA trial ( Alectnib vs chemo) for early stage NSCLC and great DFS be if it with great CNS free survival benefit as seen is ALK+ metastatic NSCLC. For early stage (stage Ib “>= 4cm to stage IIIA) NSCLC ALK+ patient” - Medical Oncology Clinical Pharmacist

“Alectinib is the first ALK inhibitor to significantly improve DFS compared with CT. Impressive curves and HR 0.24. Immediate Practice-changing trial.”-MD, PhD, Thoracic Oncology Specialist

Conclusion

The recent results from ALECENSA's ALINA trial evoke a feeling of familiarity, similar to AstraZeneca's ADAURA trial for TAGRISSO in 2020, which focused on post-surgery patients with EGFR-mutated NSCLC. At that time, TAGRISSO, a star EGFR inhibitor, showed an impressive 83% reduction in the risk of disease recurrence or death compared to a placebo when used in the adjuvant setting.

However, despite the FDA's accelerated approval of TAGRISSO as an adjuvant therapy in the same year, some medical professionals harbored doubts about this indication. Their skepticism stemmed from the lack of clear evidence that using TAGRISSO early in the course of early-stage disease could extend patients' lives, especially considering TAGRISSO's already robust performance as the standard of care for metastatic disease.

The newly disclosed findings of the ALINA study indicate that alectinib marks a groundbreaking milestone as it is the first ALK inhibitor to significantly improve DFS compared with chemotherapy and provides an effective new treatment strategy for patients with resected ALK-positive NSCLC. This development could potentially introduce a fresh therapeutic approach for this group of patients.

The company is also conducting other trials such as NAUTIKA1 (Phase II), ALNEO (Phase II), and HORIZON-01 (Phase III) in the early stage of ALK+ NSCLC. DelveInsight estimates ~5% of patients of NSCLC harbor ALK mutations. Approximately 10,000 patients were present in ALK NSCLC in the United States in 2022. 

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Anaplastic Lymphoma Kinase Non-Small Cell Lung Cancer (ALK-NSCLC) Market Insight and Forecast Report

Note: The therapeutics segment is experiencing significant NSCLC clinical trial activity, which is further expected to drive Non-Small Cell Lung Caner market growth in the coming years.