Elderly Stage III NSCLC Patients Experience Less Benefit, Greater Toxicity From Chemoradiation

Age over 70 years is associated with a lower rate of overall survival and a higher rate of adverse events with concurrent chemoradiotherapy for stage III non-small-cell lung cancer

medwireNews: Elderly patients with inoperable stage III non-small-cell lung cancer (NSCLC) achieve poorer overall survival (OS) with concurrent chemoradiotherapy than their younger counterparts, a pooled analysis of trial findings suggests.

“The similar PFS [progression-free survival] and higher rate of grade 5 AEs [adverse events] suggest early deaths were a factor in the worse OS”, say Thomas Stinchcombe, from Duke University Medical Center in Durham, North Carolina, USA, and co-workers.

While acknowledging that a higher rate of toxicity was predictable in frail patients, they note in the Journal of Clinical Oncology that the trial participants aged 70 years or older had met trial eligibility criteria and were considered to be "fit elderly".

“It seems that even fit elderly patients had comorbidities exacerbated by concurrent chemoradiotherapy, and the vulnerability of these patients was seen”, the authors write.

And they suggest: “It is also possible physicians were more conservative in the enrollment of elderly patients and more lenient in the enrollment of younger patients with comorbidities, and our analysis may have underestimated the impact of age.”

The pooled analysis used data from 16 phase II or III clinical trials comparing concurrent chemoradiotherapy alone or alongside consolidation or induction chemotherapy for unresectable stage III NSCLC between 1990 and 2012, including 2768 patients aged less than 70 years and 832 older individuals.

Median OS was 20.7 months in the younger patients versus 17.0 months for the elderly, with corresponding median PFS values of 9.1 and 8.7 months.

After adjusting for factors such as age, race, performance status and number of prior therapies, OS was significantly poorer in the older versus younger patients (hazard ratio [HR]=1.17), although PFS was comparable (HR=1.00).

The elderly patients also had a significantly higher rate of grade 3 or more severe AEs (86 vs 84%, HR=1.38) than younger individuals, including a significantly higher rate of grade 5 AEs (9 vs 4%). The older patients were also significantly less likely to complete their treatment (47 vs 57%), to stop treatment because of AEs (20 vs 13%) and to refuse any further treatment (5.8 vs 3.9%).

“Fit elderly patients with stage III NSCLC should be encouraged to receive concurrent chemoradiotherapy, preferably in clinical trials, but physicians should be cautious when monitoring the effects of therapy in elderly patients because of an increased incidence of severe toxicity”, the authors recommend.

They encourage future research to identify ways of decreasing toxicity in elderly patients, such as use of modified radiation and systemic agent protocols, and targeted therapies and immunotherapy.

“Assessment of frailty or comorbidities could potentially be used to individualize therapy by better matching patient subgroups to optimal therapies”, Thomas Stinchcombe et al suggest.

And they conclude: “Comprehensive geriatric assessment could be used to better characterize elderly patients and assess the potential for toxicity.”


Stinchcombe TE, Zhang Y, Vokes EE, et al. Pooled analysis of individual patient data on concurrent chemoradiotherapy for stage III non–small-cell lung cancer in elderly patients compared with younger patients who participated in US National Cancer Institute cooperative group studies. J Clin Oncol; Advance online publication 11 May 2017. DOI: 10.1200/JCO.2016.71.4758

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