Safety and Efficacy of Alectinib in the First Line for ALK-Mutated Lung Cancer: A Real-World Data from India

Abstract

Background

Advanced/metastatic ALK-mutated lung cancer has excellent long-term survival due availability of multiple targeted drugs. Alectinib is one of the preferred first-line therapies based on the Alex trial data. We present a real-world outcome with alectinib in first-line setting in low- and middle-income country (LMIC) like India.

Methods

We conducted a retrospective audit of ALK positive patients who received alectinib in first-line setting at the Medical Oncology Department, Tata Memorial Hospital, Mumbai, Maharashtra, India. We included patients who were started on alectinib between January 2018 and March 2022. The patients underwent routine blood and radiological evaluation every 2 to 3 months. We analyzed the data for progression-free survival (PFS), overall survival (OS), and safety profile.

Results

A total of 50 patients received alectinib in the specified period. The median age was 52.5 years (range: 28–81 years), 72% of the patients were 60 years or less; 54% of patients being male and 46% female. Eastern Cooperative Oncology Group-Performance Status (PS) 0 to 1 70%, PS 2 24%, and PS ¾ 6%. Methods for ALK testing were immunohistochemistry 92%, fluorescence in situ hybridization 2%, and next-generation sequencing 6%. The most common sites of metastasis before starting alectinib were bone (52%), pleura (42%), brain (30%), and lung (28%). Note that 66 and 33% patients received brain radiotherapy or bone-modifying agent for the central nervous system or bone metastasis, respectively. The median follow-up period was 18 months (13.1–22.8 months). Objective response rate was 76%, with partial response 74%, complete response 4%, and stable disease 16%. Median PFS and median OS were not reached, yet the expected 3-year PFS rate was 69.3% and 3-year OS rate was 85.7%, respectively. The most common sites of progression were the pleura and liver. Majority of side effects were grade 1 or 2 only with the most common being anemia, only one patient had grade 3 side effect (anemia). No drug interruption or dose modifications were needed in any patient.

Conclusion

This real-world data from LMIC confirm the safety and efficacy of alectinib in the first-line setting matching that of registration studies with similar safety and tolerance, without any new alarm.

Keywords

alectinib - ALK - anaplastic lymphoma kinase - LMIC - low- and middle-income countries - OS - overall survival - PFS - progression-free survival

Ethical Statement

The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice.

Publication History

Received: 12 June 2023

Accepted: 15 February 2025

Article published online:
03 April 2025

• References

• 1 Sung H, Ferlay J, Siegel RL. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
• 2 Noronha V, Pinninti R, Patil VM, Joshi A, Prabhash K. Lung cancer in the Indian subcontinent. South Asian J Cancer 2016; 5 (03) 95-103
• 3 Nagl L, Pall G, Wolf D, Pircher A, Horvath L. Molecular profiling in lung cancer. Memo Mag Eur Med Oncol 2022; 15 (01) 1-5
• 4 Guérin A, Sasane M, Zhang J. et al. ALK rearrangement testing and treatment patterns for patients with ALK-positive non-small cell lung cancer. Cancer Epidemiol 2015; 39 (03) 307-312
• 5 Kang HJ, Lim HJ, Park JS. et al. Comparison of clinical characteristics between patients with ALK-positive and EGFR-positive lung adenocarcinoma. Respir Med 2014; 108 (02) 388-394
• 6 Solomon BJ, Mok T, Kim D-W. et al; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371 (23) 2167-2177
• 7 Tan DSW, Araújo A, Zhang J. et al. Comparative efficacy of ceritinib and crizotinib as initial ALK-targeted therapies in previously treated advanced NSCLC: an adjusted comparison with external controls. J Thorac Oncol 2016; 11 (09) 1550-1557
• 8 Peters S, Camidge DR, Shaw AT. et al; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017; 377 (09) 829-838
• 9 Hoang T, Myung SK, Pham TT, Park B. Efficacy of crizotinib, ceritinib, and alectinib in ALK-positive non-small cell lung cancer treatment: a meta-analysis of clinical trials. Cancers (Basel) 2020; 12 (03) 526
• 10 Pan Y, Deng C, Qiu Z, Cao C, Wu F. The resistance mechanisms and treatment strategies for ALK-rearranged non-small cell lung cancer. Front Oncol 2021; 11: 713530
• 11 Chia PL, Mitchell P, Dobrovic A, John T. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clin Epidemiol 2014; 6: 423-432
• 12 Wrona A. Management of CNS disease in ALK-positive non-small cell lung cancer: is whole brain radiotherapy still needed?. Cancer Radiother 2019; 23 (05) 432-438
• 13 Shaw AT, Gandhi L, Gadgeel S. et al; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol 2016; 17 (02) 234-242 cited 2022Sep3 [Internet]
• 14 Soria JC, Tan DSW, Chiari R. et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet 2017; 389 (10072): 917-929