Impact of Chemotherapy Dose Reductions on Survival Outcomes Among Older NSCLC Patients Without Actionable Mutations

Официальное название

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

Обзор

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 study seeks to evaluate chemotherapy dosing patterns and associated survival outcomes in older patients.

Подробное описание

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.

Вмешательства

• Другое Progression free survival
  PFS
• Другое Overall survival
  OS

Первичные конечные точки

• To compare the overall survival (OS) between older NSCLC patients treated with standard-dose versus reduced-dose first-line platinum-doublet chemotherapy OR single agent non-platinum chemotherapy. [Срок оценки: From enrollment to the end of study on 31 Dec 2026]

Вторичные конечные точки (2)

• To compare the progression free survival (PFS) between older NSCLC patients treated with standard-dose versus reduced-dose first-line platinum-doublet chemotherapy OR single agent non-platinum chemotherapy. [Срок оценки: From enrollment to end of study on 31 Dec 2026]
• To assess objective response rates in patients who complete FOUR cycles of chemotherapy. [Срок оценки: From enrollment to end of study period on 31 Dec 2026]

Критерии участия

Критерии включения

• Age ≥65 years
• Histologically confirmed stage IV NSCLC
• Negative for EGFR mutation, ALK rearrangement, and ROS1 fusion
• Treated with at least ONE cycle of first-line chemotherapy

Критерии исключения

• Patients who received targeted therapy or immunotherapy as monotherapy in the first-line setting
• Incomplete survival data

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Малайзия · 3 центра

• Hospital Tengku Ampuan Afzan — Kuantan
• Hospital Wanita dan Kanak-Kanak Sabah — Kota Kinabalu
• Universiti Malaya Medical Centre — Kuala Lumpur

Гонконг · 1 центр

• Queen Mary Hospital, The University of Hong Kong — Гонконг

Публикации

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• 7. Sedrak MS, Sun CL, Liu X, et al. Aging and tolerance to chemotherapy: Impact of dose reduction and treatment delays on survival outcomes. Journal of Clinical Oncology, 2021 39, 1714-1723.
• Hurria A, Kris MG. Management of lung cancer in older adults. CA Cancer J Clin. 2003 Nov-Dec;53(6):325-41. doi: 10.3322/canjclin.53.6.325. PMID 15224973
• Maione P, Perrone F, Gallo C, Manzione L, Piantedosi F, Barbera S, Cigolari S, Rosetti F, Piazza E, Robbiati SF, Bertetto O, Novello S, Migliorino MR, Favaretto A, Spatafora M, Ferrau F, Frontini L, Bearz A, Repetto L, Gridelli C, Barletta E, Barzelloni ML, Iaffaioli RV, De Maio E, Di Maio M, De Feo G, Sigoriello G, Chiodini P, Cioffi A, Guardasole V, Angelini V, Rossi A, Bilancia D, Germano D, La PMID 16192578
• Sundararajan V, Hershman D, Grann VR, Jacobson JS, Neugut AI. Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study. J Clin Oncol. 2002 Jan 1;20(1):173-8. doi: 10.1200/JCO.2002.20.1.173. PMID 11773167
• 3. Liam, Chong-Kin, Toh-Yoon Evelyn Goh, Nur Syafikah Shamsudin, and Chee-Chee Khoo. 2022. "Driver Gene Alterations and PD-L1 Expression in Non-Small Cell Lung Cancer and Their Association with Smoking and Gender in a Malaysian Population." Asian Pacific Journal of Cancer Prevention 23 (6): 1911-1917.

Идентификаторы

NCT: NCT07369596 · 20258615434

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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