Systemic Therapy for Elderly Patients With Advanced Non–Small-Cell Lung Cancers

Lung cancer is the leading cause of cancer-related death worldwide, and in the United States, nearly 50% of patients with advanced lung cancer are age 70 years or older.1 Systemic therapies are required to improve survival outcomes for these patients, but toxicity rates of most therapies are higher in these populations and comorbidities may limit the choice of therapy.2,3 Most studies in elderly patients have focused on the role of chemotherapy in fit patients (those having performance status [PS] 0 to 1), including the article presenting the results of the MILES-3 (Cisplatin in Combination With Gemcitabine for Elderly Patients With Lung Cancer) and MILES-4 (Study Comparing Gemcitabine and Pemetrexed, With or Without Cisplatin, in Patients With Nonsquamous Lung Cancer) studies in this issue of Journal of Clinical Oncology.4

The MILES-3 and MILES-4 studies included patients older than age 69 years with PS 0 to 1, and randomly assigned patients to gemcitabine or pemetrexed with or without cisplatin. Unfortunately, both trials closed before completion because of slow accrual, so the results were combined for analysis in Gridelli et al.4 The authors report that progression-free survival (PFS) and objective response rate (ORR) were significantly superior in the cisplatin arms, and although overall survival (OS) was favored in the cisplatin arms, the difference was not statistically significant (hazard ratio [HR], 0.76; 95% CI, 0.70 to 1.05; P = .4). The cisplatin arms showed more severe hematologic toxicity, fatigue, and anorexia. The authors concluded that cisplatin-based doublets should not be standard first-line therapy for elderly patients with non–small-cell lung cancer (NSCLC). However, this conclusion should not be applied for all doublet chemotherapies, especially those using carboplatin and/or pemetrexed. In addition, the conclusions do not apply to newer molecular-based therapies or to immunotherapies, which are discussed in this editorial.

With respect to chemotherapy, data are limited to patients with PS 0 to 1, and fitness for chemotherapy varies considerably among elderly patients with PS 0 to 1 because of factors such as multiple chronic conditions, polypharmacy, geriatric syndromes, and frailty.5 There is some evidence that comprehensive geriatric assessments using published scales may help guide treatment decisions, but these scales may not be superior to clinical judgment alone.5

A Cochrane database review of randomized trials comparing non-platinum- versus platinum-based therapy showed superior OS and PFS for the platinum-based combinations.3 Other randomized trials showed that platinum doublet therapy was superior to single-agent therapy but with an increase in toxicity.1,6 Exploratory analyses showed greater benefit for carboplatin-based combinations (HR, 0.76) compared with cisplatin-based combinations (HR, 0.91).2 Adverse events (AEs) were more frequent in the platinum combinations, especially cisplatin-based combinations. Non-platinum combinations have not been proven to improve OS compared with single agents. In patients with nonsquamous NSCLC, pemetrexed combinations have a more favorable toxicity profile,7 and the benefit of pemetrexed is similar in elderly and younger patients.8 We concluded that pemetrexed-carboplatin can be recommended for fit elderly patients with NSCLC with a nonsquamous histology and that carboplatin combined with nab-paclitaxel, paclitaxel,9,10 or gemcitabine11 can be recommended for fit elderly patients with squamous NSCLC. Single-agent chemotherapy can be considered for less fit patients.

Journal of Clinical Oncology , éditorial en libre accès, 2017

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