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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Carcinoma NSCLC
• Intervention / Treatment: Other: Progression free survival; Other: Overall survival

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Mau Ern Poh, MBBS; Phone Number: +60379494422; Email: ernestpoh@um.edu.my
• Study Contact Backup: Name: Danouska Bala Krishnan; Phone Number: +603-79492351; Email: danouska@ummc.edu.my

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital, The University of Hong Kong
    • Contact: Wang Chun Kwok; Phone Number: +85222556208; Email: kwokwch@hku.hk
    • Principal Investigator: Chun Kwok Wang
• Malaysia
  • Kuala Lumpur, Malaysia
    • Recruiting
    • Universiti Malaya Medical Centre
    • Contact: Mau Ern Poh, MBBS; Phone Number: +60379494422; Email: ernestpoh@um.edu.my
    • Principal Investigator: Mau Ern Poh
  • Pahang
    • Kuantan, Pahang, Malaysia
      • Recruiting
      • Hospital Tengku Ampuan Afzan
      • Contact: Sin Nee Tan; Phone Number: +6095572222; Email: christine0507@live.com
      • Principal Investigator: Sin Nee Tan
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia
      • Recruiting
      • Hospital Wanita dan Kanak-Kanak Sabah
      • Contact: Seng Wee Cheo; Phone Number: +6088522600; Email: cheosengwee@gmail.com
      • Principal Investigator: Seng Wee Cheo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Retrospective cohort study using data from three centres in Malaysia from 2020 to 2025. All patients aged ≥65 years with advanced/metastatic NSCLC and no actionable driver mutations who received AT LEAST ONE CYCLE of first-line chemotherapy will be included in the analysis.

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal dose group; Patients receiving standard dose of chemotherapy	Other: Progression free survival; PFS; Other: Overall survival; OS
Dose reduction group; Patients receiving lower doses of chemotherapy	Other: Progression free survival; PFS; Other: Overall survival; OS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	From enrollment to the end of study on 31 Dec 2026

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	From enrollment to end of study on 31 Dec 2026
To assess objective response rates in patients who complete FOUR cycles of chemotherapy.	From enrollment to end of study period on 31 Dec 2026

Collaborators and Investigators

• Sponsor: University of Malaya
• Investigators: Principal Investigator: Mau Ern Poh, MBBS, Universiti Malaya

Publications and helpful links

General Publications

• Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V, Klapper S, Hansen K, Ramani R, Lachs M, Wong FL, Tew WP. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011 Sep 1;29(25):3457-65. doi: 10.1200/JCO.2011.34.7625. Epub 2011 Aug 1.
• Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.
• Tan DS, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA Jr, Mok TS, Hirsch FR. The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016. J Thorac Oncol. 2016 Jul;11(7):946-63. doi: 10.1016/j.jtho.2016.05.008. Epub 2016 May 23.
• Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. doi: 10.1056/NEJMoa1408440.
• 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.
• 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.
• 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.
• 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, Lamberti A, Pontillo V, Brancaccio L, Renda F, Romano F, Esani G, Gambaro A, Vinante O, Azzarello G, Clerici M, Bollina R, Belloni P, Sannicolo M, Ciuffreda L, Parello G, Cabiddu M, Sacco C, Sibau A, Porcile G, Castiglione F, Ostellino O, Monfardini S, Stefani M, Scagliotti G, Selvaggi G, De Marinis F, Martelli O, Gasparini G, Morabito A, Gattuso D, Colucci G, Galetta D, Giotta F, Gebbia V, Borsellino N, Testa A, Malaponte E, Capuano MA, Angiolillo M, Sollitto F, Tirelli U, Spazzapan S, Adamo V, Altavilla G, Scimone A, Hopps MR, Tartamella F, Ianniello GP, Tinessa V, Failla G, Bordonaro R, Gebbia N, Valerio MR, D'Aprile M, Veltri E, Tonato M, Darwish S, Romito S, Carrozza F, Barni S, Ardizzoia A, Corradini GM, Pavia G, Belli M, Colantuoni G, Galligioni E, Caffo O, Labianca R, Quadri A, Cortesi E, D'Auria G, Fava S, Calcagno A, Luporini G, Locatelli MC, Di Costanzo F, Gasperoni S, Isa L, Candido P, Gaion F, Palazzolo G, Nettis G, Annamaria A, Rinaldi M, Lopez M, Felletti R, Di Negro GB, Rossi N, Calandriello A, Maiorino L, Mattioli R, Celano A, Schiavon S, Illiano A, Raucci CA, Caruso M, Foa P, Tonini G, Curcio C, Cazzaniga M. Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study. J Clin Oncol. 2005 Oct 1;23(28):6865-72. doi: 10.1200/JCO.2005.02.527.
• 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.
• Hamaker ME, Schiphorst AH, ten Bokkel Huinink D, Schaar C, van Munster BC. The effect of a geriatric evaluation on treatment decisions for older cancer patients--a systematic review. Acta Oncol. 2014 Mar;53(3):289-96. doi: 10.3109/0284186X.2013.840741. Epub 2013 Oct 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: January 17, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 30, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; NSCLC; older patients
• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Diagnosis; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Statistics as Topic; Prognosis; Treatment Outcome; Survival Analysis; Progression-Free Survival
• Other Study ID Numbers: 20258615434

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No