Journal Article

Treatment sequencing after failure to alectinib in patients with anaplastic lymphoma kinase‐positive non‐small‐cell lung cancer

Ihara, Yasutaka, Yoshida, Hisako, Shintani, Ayumi, Imai, Takumi, Shimomura, Yuki, Sawa, Kenji

2024

Overview

Alectinib is the first‐line therapy for anaplastic lymphoma kinase‐positive non‐small‐cell lung cancer. Although some guidelines have recommended using other anaplastic lymphoma kinase inhibitors after alectinib failure, evidence for such regimens in patients who fail to respond to alectinib is limited. This study involved using administrative claims data from acute care hospitals in Japan. We extracted the data of 634 patients diagnosed with lung cancer between September 1, 2014, and January 31, 2023, who received alectinib treatment before treatment with another anaplastic lymphoma kinase inhibitor. We assessed distributions of patients according to their treatment sequencing and prognosis among three periods defined based on the initial marketing dates of lorlatinib and brigatinib. The type of anaplastic lymphoma kinase inhibitors after alectinib failure changed over time. In the most recent period, lorlatinib (58%) and brigatinib (40%) became predominant. Two‐year overall survival improved over time (47%–84%), accompanied by an increased 2‐year proportion of patients who continuously used anaplastic lymphoma kinase inhibitors after alectinib failure (13%–44%). The times to treatment discontinuation of the regimen between patients treated with lorlatinib and brigatinib were similar, with a hazard ratio of 1.02 (95% confidence interval, 0.64–1.64) in the period after marketing brigatinib. This study provides insights into the evolving treatment landscape for patients with anaplastic lymphoma kinase‐positive non‐small‐cell lung cancer who experience failed alectinib treatment and highlights the need for further studies and data accumulation to determine the optimal treatment strategy. Alectinib is the preferred initial treatment for anaplastic lymphoma kinase (ALK)‐positive non‐small‐cell lung cancer, but when it fails, there is limited evidence for using other ALK inhibitors. This study observed changing trends in post‐alectinib treatment patterns, with lorlatinib and brigatinib becoming more common and 2‐year survival and 2‐year times to treatment discontinuation of the regimen improved over time. Our study provides insights into the evolving treatment landscape for patients with ALK‐positive non‐small‐cell lung cancer who experience failed alectinib treatment.

• Publisher: John Wiley & Sons, Inc
• Subject: administrative claims database / alectinib / Aminopyridines / anaplastic lymphoma kinase / Anaplastic Lymphoma Kinase - genetics / Body mass index / brigatinib / Cancer therapies / Carbazoles / Carcinoma, Non-Small-Cell Lung - chemically induced / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Chemotherapy / Enzyme inhibitors / Hospitals / Humans / Kinases / Lactams / Lactams, Macrocyclic / lorlatinib / Lung cancer / Lung Neoplasms - chemically induced / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lymphoma / Marketing / Medical prognosis / Metastasis / Missing data / Non-small cell lung carcinoma / Organophosphorus Compounds / Patients / Piperidines / Protein Kinase Inhibitors - pharmacology / Protein-tyrosine kinase / Pyrazoles / Pyrimidines