“Our results suggest that elderly patients could have worse survival outcomes with immunotherapy than younger patients, without differences in terms of toxicity,” said authors of the first study.
“In elderly patients with advanced NSCLC with PD-L1–positive tumors, pembrolizumab monotherapy improved overall survival over chemotherapy, together with a more favorable safety profile,” said authors of the second study.
Two studies reported at the European Lung Cancer Congress (ELCC) 2019 provided new insights on the efficacy and safety of immunotherapy in elderly patients with advanced non–­small cell lung cancer (NSCLC).
Although around half of all people newly diagnosed with NSCLC are elderly (Pallis et al, Annals of Oncology), there is currently limited evidence on the efficacy and safety of immunotherapy in this age group due to their underrepresentation in clinical trials. There have also been concerns that age-related decline in the immune system might affect the efficacy of immunotherapy in older patients.
A retrospective study of patients with advanced NSCLC treated with immunotherapy in real-life clinical practice suggested that elderly patients (≥ 70 years) may have shorter overall survival than younger patients—but demonstrated that toxicity seen with immunotherapy was similar between the age groups. These findings were presented by Corral de la Fuente et al (Abstract 169P_PR).
Researchers retrospectively reviewed all patients with advanced NSCLC treated with immunotherapy agents at Hospital Universitario Ramon y Cajal between 2014 and 2018. Just over 1 in 4 (27 patients; 27.5%) of the 98 patients treated with immunotherapy agents over this 4-year period were aged 70 years or older. Programmed cell death ligand 1 (PD-L1) status was known in 50% of patients.
Overall survival in these elderly patients was significantly shorter than in patients younger than 70 years of age (median = 5.5 vs 13 months; hazard ratio [HR] = 3.86, 95% confidence interval [CI] = 2.073–7.214; P < .0001). Progression-free survival was also significantly shorter in elderly patients than in younger patients (1.8 vs 3.6 months, HR = 2.1, 95% CI = 1.181–3.744, P = .012). There were no statistically significant differences in immune-related adverse events between elderly and younger patients (P = .535).
The study showed that immunotherapy was administered mainly as second-line treatment (61% of patients) or third-line or later (24.5%) across the entire group of 98 patients of all ages. Just over half (52%) were treated with nivolumab.
A second study pooling data from three randomized trials showed significantly improved overall survival in elderly patients with advanced PD-L1–positive NSCLC treated with the immunotherapy agent pembrolizumab compared to those treated with chemotherapy. These findings were presented by Nosaki et al (Abstract 103O_PR).
The study compared the efficacy and safety results for 264 elderly patients aged ≥ 75 years in the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 trials with results for 2,292 trial participants younger than 75 years. All of the patients had PD-L1 tumor proportion scores (PD-L1 TPS) of 1% or higher, and half of the elderly group in this analysis had scores of at least 50%.
Results show significantly improved overall survival in elderly patients with PD-L1 tumors scores ≥ 1% treated with pembrolizumab compared to those treated with chemotherapy (HR = 0.76, 95% CI = 0.56–1.02). The improvement in overall survival with pembrolizumab compared to chemotherapy was even greater in patients with PD-L1 tumor scores ≥ 50% (HR = 0.41, 95% CI = 0.23–0.73). One-year overall survival rates with pembrolizumab in elderly patients were comparable to those in younger patients (53.7% vs 54.9% in PD-L1 TPS ≥ 1% and 61.7% vs 61.7% in PD-L1 TPS ≥ 50%).
Fewer elderly patients treated with pembrolizumab had treatment-related adverse events compared to those treated with chemotherapy (68% vs 94%). Grade 3 to 5 treatment-related adverse events in elderly patients were also less common with pembrolizumab compared to chemotherapy (24% vs 61%). Common treatment-related adverse events with pembrolizumab in elderly patients were fatigue (17.4%), decreased appetite (12.8%), and pruritus (12.8%). Immune-mediated adverse events and infusion reactions were more frequent with pembrolizumab vs chemotherapy in the elderly group of patients (25% vs 7%), but showed no difference compared to younger patients treated with pembrolizumab (25%).
Considering potential limitations, Dr. Nosaki noted that the elderly patients included in the pooled analysis met the inclusion criteria for each of the individual studies, which would have selected for a relatively fit elderly patient population.
In terms of limitations, she noted that PL-1 expression was known in only 50% of patients included in the real-world study and that data were collected retrospectively. “Data collected in real-world studies are not controlled as precisely as in randomized trials,” she noted, but added that elderly patients are generally underrepresented in clinical trials.
Disclosure: The study authors’ full disclosures can be found on ELCC’s Conference Calendar.