Radiation Therapy and Checkpoint Inhibitors in Older Patients with Metastatic Non-Small Cell Lung Cancer

Abstract

Checkpoint inhibitors (CPI), combined with radiation therapy (RT), are being incorporated into the treatment of advanced lung cancer (Antonia et al, Lancet 2017), however the safety and efficacy of CPIs in the elderly is unclear. Recent analysis of the KEYNOTE-001 trial showed improved outcomes among patients who received RT prior to CPIs (Shaverdian et al, Lancet Onc 2018). Thus far, no trials have investigated whether treatment response or risk of adverse events (SAEs) for CPIs and RT differ among older adults. We performed a single-institution, retrospective chart review of patients diagnosed with lung cancer who received >4 weeks of PD-1/PDL-1 or CTLA-4 blockade between 2010-2016 with manual abstraction of demographic and clinical covariates. Best response (per RECIST1.1), time to treatment failure (TTF), progression-free (PFS), and overall survival (OS) were defined from date of first CPI infusion. Treatment failure includes CPI discontinuation or initiation of new treatment. All analyses, including Kaplan-Meier (KM) or Cox-Proportional Hazard (Cox) survival analyses, were performed using the statistical software R. A total of 125 of 182 evaluable patients treated with CPIs for NSCLC met all inclusion criteria. Median age at diagnosis was 65 (34-87). 52.8% were female. 64% were former smokers. 70.4% were adenocarcinomas. 59.2% were metastatic at diagnosis. CPIs included pembrolizumab (45%), nivolumab (42%), dual PD-1/CTLA-4 blockade (6%), other CPI (7%). 11.2% had clinically confirmed grade 2 or greater SAEs. 69.6% received RT, 43.2% occurred >3 months prior to CPI. RT with CPI was defined as patients receiving RT 1-3 months before CPI (10%), within 1 month of CPI (9%), and >1 month after CPI (18%). None of these variables were associated with older age (Fisher’s Exact Test, p>0.05). Complete/partial response, stable disease or progressive disease was achieved in 30.4%, 28.8% and 40.8%, respectively; response was independent of age (p=0.21). On KM analysis, older age was associated with improved PFS (HR=0.74, 95% CI=0.554-0.997), and RT to a Non-CNS site at the time of CPI was associated with improved PFS [HR=0.59 (0.34-1.01)). On multivariate Cox analysis, older age (Adjusted HR ‘AHR’=0.68, p<0.021) and RT to a Non-CNS site (AHR=0.46, p<0.009) were prognostic for PFS. Similar trends were observed for TTF. Older age and RT (irrespective of timing or site) were not associated with OS (p>0.1). Among patients receiving CPIs for the treatment of advanced lung cancer, older age is not associated with a worse OS or higher rates of SAEs, but may be associated with improved PFS and TTF. Prospective data is needed to better examine the impact of RT on OS in the setting of CPIs for older patients.Abstract 1141; TableAgeRTOS HRMedian TTF (weeks)Median PFS (weeks)<65None1.0012.313.9CNS0.81 (0.24-2.73)11.912.5Non-CNS0.61 (0.26-1.44)31.830.8>=65None0.73 (0.38-1.38)24.124.1CNS1.09 (0.44-2.73)21.325.2Non-CNS0.68 (0.23-1.99)80.492.8OverallNA21.023.1 Open table in a new tab