Impact of Chemotherapy Dose Reductions on Survival Outcomes Among Older NSCLC Patients Without Actionable Mutations: A Retrospective Cohort Study.

Lung cancer remains the leading cause of cancer-related mortality globally, responsible for approximately 1.8 million deaths annually. Non-small cell lung cancer (NSCLC) comprises about 85% of all lung cancer cases, with adenocarcinoma (ADC) now the predominant histological subtype. In Malaysia, NSCLC is similarly the most common form of lung cancer, with high proportions of EGFR and ALK mutations in certain subgroups.

Despite the emergence of targeted therapy and immunotherapy, cytotoxic chemotherapy, particularly platinum-based doublets remains the backbone of treatment for many NSCLC patients lacking actionable mutations. These patients often present with advanced disease and limited survival prospects, with median overall survival (OS) of 8- 10 months. These includes older patients with advanced NSCLC and no actionable mutations who depend on chemotherapy for disease control.

Clinical decisions regarding dosing are frequently influenced by perceptions of frailty rather than individual fitness. Evidence suggests that appropriately selected older adults can tolerate standard-dose chemotherapy and achieve survival outcomes comparable to younger patients. However, older adults are usually under-represented in clinical trials and often receive reduced doses of chemotherapy due to concerns regarding age-related frailty, polypharmacy, and toxicity. This raises an important question: does dose reduction compromise survival outcomes in older NSCLC patients?

This study seeks to address this knowledge gap by retrospectively evaluating chemotherapy dosing patterns and associated survival outcomes in older patients treated at three centres in Malaysia: Universiti Malaya Medical Centre (UMMC), Hospital Tengku Ampuan Afzan, Kuantan and Hospital Wanita dan Kanak-kanak, Likas, Sabah and one centre in Hong Kong: Queen Mary Hospital, The University of Hong Kong. It will evaluate whether chemotherapy dose reductions are associated with poorer survival outcomes in older NSCLC patients. It will also assess clinical predictors such as ECOG performance status, BMI, comorbidities, and gender to identify factors influencing treatment tolerance and survival.