First-line Treatment in Elderly Patients with Advanced Non-small Cell Lung Cancer

Review Article

Austin J Cancer Clin Res 2015;2(5): 1043.

First-line Treatment in Elderly Patients with Advanced Non-small Cell Lung Cancer

Asami K¹* and Atagi S²

¹Department of Clinical Oncology, Machida Clinic, Japan

²Department of Clinical Oncology, National Hospital Organization Kinki-chuo Chest Medical Center, Japan

*Corresponding author: Asami K, Department of Clinical Oncology, Machida Clinic, 4F Sunwood-machida 4-15-13 Hara-machida, Machida City, Tokyo, 194-0013,Japan.

Received: May 18, 2015;Accepted: June 15, 2015;Published: July 29, 2015


Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide, and more than 40% of patients are 70 years or older at the time of diagnosis. Based on the results of previous large-scale randomized phase III trials of elderly patients with advanced NSCLC, several single-agent chemotherapy regimens have been recommended as first-line treatment.

Recently, a large-scale clinical trial of targeted tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) significantly prolonged survival and resulted in high response rates compared with standard chemotherapy as first-line treatment in patients with advanced NSCLC harboring EGFR mutations or the ALK fusion gene.

Although various first-line treatment options are currently available for patients with advanced NSCLC, it is unclear whether any of these treatments are advantageous in the first-line treatment of elderly patients. This review focuses on chemotherapy regimens and targeted agents, especially for EGFR, ALK, and vascular endothelial growth factor, based on the latest clinical data.

Keywords: Chemotherapy; Elderly patients; First-line therapy; Non-small cell lung cancer; Targeted therapy


NSCLC: non-small cell lung cancer; EGFR: epidermal growth factor receptor; EML4-ALK: echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase; VEGF: vascular endothelial growth factor; RR: response rate; PFS: progressionfree survival; QOL: quality of life; HR: hazard ratio; CI: confidence interval; PS: performance status; OS: overall survival; OR: odds ratio; AUC: area under the concentration-time curve; HR: hazard ration; HER: human epidermal receptor


Lung cancer is most frequently diagnosed in people aged 65–74 years, with the median age at diagnosis being 70 years based on the Surveillance, Epidemiology, and End Results Program (https://seer., and mortality rates from this disease have increased among patients aged 70 years or older [1-2]. Many elderly patients with non-small cell lung cancer (NSCLC) have comorbidities and decreases in bone marrow capability, renal function, and drug clearance, which could negatively affect the severity of treatmentrelated toxicity. Although many clinical trials of patients with advanced NSCLC have been conducted, elderly patients aged 65 years or older accounted for only one-quarter of all participants, and only a few large-scale clinical trials of elderly patients with NSCLC have been designed [3-4].

In recent years, front-line molecular targeted therapies targeting specific oncogenes such as epidermal growth factor receptor (EGFR) mutations and the echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene have greatly influenced survival and response in patients with advanced NSCLC harboring these specific oncogenes. An anti-growth factor vascular endothelial growth factor (VEGF) monoclonal antibody inhibitor combined with chemotherapy produced a higher response rate (RR) and longer progression-free survival (PFS) than standard chemotherapy for non-squamous cell NSCLC.

Currently, various therapies are offered as first-line treatments in elderly patients with advanced NSCLC. Here, we reviewed the frontline treatment strategy in elderly patients with advanced NSCLC with a focus on systemic chemotherapy and molecular targeted therapies.

Single-agent chemotherapy and non-platinum–doublet chemotherapy in non-selected elderly patients with advanced NSCLC

Among previous several phase III trials of non-platinum agents in elderly patients aged 70 years or older with advanced NSCLC; the ELVIS trial revealed that vinorelbine improved survival and quality of life (QOL) in patients compared to best supportive care [5]. Chemotherapy with vinorelbine significantly prolonged survival in the treatment group compared to the control group (6.9 months vs. 4.9 months, hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.45–0.93, p = 0.03). Table 1 presents previous phase III trials of single-agent or combination chemotherapy using third-generation cytotoxic agents including gemcitabine, vinorelbine, and docetaxel in patients with advanced NSCLC [5-8]. Although combination chemotherapy with third-generation cytotoxic agents including gemcitabine and vinorelbine produced a higher RR than a single third-generation agent, no significant survival advantage was noted between combination and single-agent chemotherapy regimens excluding the trial conducted by Frasci el al. additionally, higher rates of toxicity were observed for the gemcitabine plus vinorelbine regimen than for the single-agent regimens. A subset analysis of some phase III trials comparing doublet chemotherapy with third-generation cytotoxic agent monotherapy for advanced NSCLC reported a higher RR and longer PFS in patients treated with doublet chemotherapy [9- 10]. However, no significant difference was noted in survival between double and single-agent chemotherapy. Elderly patients aged 70 years or older and patients with a performance status (PS) of 2 were eligible for inclusion in these trials (Table 1). The RRs and overall survival (OS) times were 23–32% and 5.5–9.7 months, respectively, for gemcitabine-based combination chemotherapy including paclitaxel, vinorelbine, and docetaxel, compared to 13–18% and 5.1–6.4 months, respectively, for third-generation single-agent chemotherapy. Russo et al. reported in their literature-based meta-analysis of nonplatinum chemotherapy for elderly patients with advanced NSCLC that although gemcitabine-based doublet chemotherapy was advantageous regarding RR, no survival benefit was noted between gemcitabine-based doublet chemotherapy and monotherapy with third-generation agents such as vinorelbine, docetaxel, and paclitaxel [11]. Based on their analysis of the data of four eligible phase III trials including a total of 1436 elderly patients with NSCLC, a statistically significant increase in the overall RR favoring doublet regimens was observed (odds ratio [OR] = 0.65, 95% CI = 0.51–0.82, p < 0.001). Conversely, no statistical difference in 1-year survival rates was noted between double and single-agent chemotherapy (OR = 0.78, 95% CI = 0.57–1.06, p = 0.169). The incidence of grade 3–4 toxicities did not differ significantly between the arms excluding thrombocytopenia (OR = 1.76, 95% CI = 1.12–2.76, p = 0.014).