Systemic therapy for advanced non-small cell lung cancer in elderly patients and patients with a poor performance status
- Rogerio C Lilenbaum, MD, FACP
Rogerio C Lilenbaum, MD, FACP
- Section Editor — Lung Cancer
- Yale Cancer Center
Treatment of patients with lung cancer depends upon the cell type (non-small cell versus small cell), tumor stage, molecular characteristics, and an assessment of the patient's overall medical condition. (See "Overview of the initial evaluation, treatment and prognosis of lung cancer".)
Patients with stage I, II, or III non-small cell lung cancer (NSCLC) are generally treated with curative intent using surgery, radiation therapy (RT), or a combined-modality approach that may also include chemotherapy (table 1). By contrast, patients with advanced NSCLC are frequently treated with palliative intent using systemic therapy. This includes patients who present with stage IV disease and those who relapsed following prior definitive treatment. (See "Overview of the treatment of advanced non-small cell lung cancer".)
Age and comorbidity may limit the ability to deliver therapy for advanced NSCLC. The median age of patients with newly diagnosed NSCLC in developed countries is approximately 68 years, and up to 40 percent are aged ≥70 years at diagnosis . Furthermore, patients with a borderline or poor performance status (ie, ECOG performance status ≥2 [(table 2)] or Karnofsky Performance Status (KPS) ≤70 [(table 3)]) comprise 30 to 40 percent of patients with advanced NSCLC . Such patients have often either been excluded from or are underrepresented in clinical trials.
The development of agents that target specific pathways involved in the development or progression of NSCLC has provided an alternative to chemotherapy and has led to a personalized approach to the treatment of advanced NSCLC. Targeted agents tend to be better tolerated and may have an important role in older patients and those with significant comorbidity. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer".)
Systemic therapy in elderly and poor performance status patients with advanced NSCLC is discussed here.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Surveillance Epidemiology and End Results database. http://seer.cancer.gov/ (Accessed on September 08, 2010).
- Lilenbaum RC, Cashy J, Hensing TA, et al. Prevalence of poor performance status in lung cancer patients: implications for research. J Thorac Oncol 2008; 3:125.
- Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol 2013; 8:823.
- Moran T, Sequist LV. Timing of epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung cancer with EGFR mutations. J Clin Oncol 2012; 30:3330.
- Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst 1999; 91:66.
- Kudoh S, Takeda K, Nakagawa K, et al. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol 2006; 24:3657.
- Azzoli CG, Baker S Jr, Temin S, et al. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 2009; 27:6251.
- Gridelli C, Ardizzoni A, Le Chevalier T, et al. Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel. Ann Oncol 2004; 15:419.
- Quoix E, Zalcman G, Oster JP, et al. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet 2011; 378:1079.
- Gridelli C, Perrone F, Gallo C, et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003; 95:362.
- Lilenbaum R, Villaflor VM, Langer C, et al. Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2: prognostic factors and treatment selection based on two large randomized clinical trials. J Thorac Oncol 2009; 4:869.
- Zukin M, Barrios CH, Pereira JR, et al. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol 2013; 31:2849.
- Abe T, Takeda K, Ohe Y, et al. Randomized phase III trial comparing weekly docetaxel plus cisplatin versus docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small-cell lung cancer: the intergroup trial JCOG0803/WJOG4307L. J Clin Oncol 2015; 33:575.
- Schuette W, et al. 65 plus: A randomized phase III trial of pemetrexed and bevacizumab versus pemetrexed, bevacizumab, and carboplatin as first-line treatment for elderly patients with advanced nonsquamous, non-small cell lung cancer (abstract 8013). American Society of Clinical Oncology 2013 meeting.
- Ramalingam SS, Dahlberg SE, Langer CJ, et al. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol 2008; 26:60.
- Leighl NB, Zatloukal P, Mezger J, et al. Efficacy and safety of bevacizumab-based therapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer in the phase III BO17704 study (AVAiL). J Thorac Oncol 2010; 5:1970.
- Zhu J, Sharma DB, Gray SW, et al. Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA 2012; 307:1593.
- Crinò L, Cappuzzo F, Zatloukal P, et al. Gefitinib versus vinorelbine in chemotherapy-naive elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized, phase II study. J Clin Oncol 2008; 26:4253.
- Jackman DM, Yeap BY, Lindeman NI, et al. Phase II clinical trial of chemotherapy-naive patients > or = 70 years of age treated with erlotinib for advanced non-small-cell lung cancer. J Clin Oncol 2007; 25:760.
- Lee SM, Rudd R, Khan I, et al. TOPICAL: Randomized phase III trial of erlotinib compared with placebo in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) and unsuitable for first-line chemotherapy (abstract #7504). J Clin Oncol 2010; 28:540s.
- Langer CJ. The "lazarus response" in treatment-naive, poor performance status patients with non-small-cell lung cancer and epidermal growth factor receptor mutation. J Clin Oncol 2009; 27:1350.
- Inoue A, Kobayashi K, Usui K, et al. First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol 2009; 27:1394.
- CHEMOTHERAPY VERSUS TARGETED THERAPY
- Initial therapy
- Subsequent therapy
- SYSTEMIC CHEMOTHERAPY
- Single agent chemotherapy
- - Vinorelbine
- - Docetaxel
- - Other single agents
- Combination versus single agent chemotherapy
- Chemotherapy plus bevacizumab
- TARGETED THERAPY
- EGFR mutation
- ALK fusion oncogene
- ROS1 translocation
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS