Studies show varying efficacy of immunotherapy in elderly patients with lung cancer
Pembrolizumab monotherapy extended OS compared with chemotherapy among elderly patients with advanced non-small cell lung cancer, according to results of a pooled data analysis presented at European Lung Cancer Congress.
However, a separate retrospective study of immunotherapy outcomes presented at the meeting suggested elderly patients with NSCLC could have shorter OS than younger patients, with no difference in toxicity between age groups.
About 70% of newly diagnosed patients with NSCLC are elderly, and more than half have locally advanced or metastatic disease. However, data on the safety and efficacy of immunotherapy among these older patients is limited because they are routinely underrepresented in clinical trials.
In the first study, researchers pooled data from three randomized controlled trials comparing pembrolizumab (Keytruda, Merck) monotherapy with standard chemotherapy among patients with PD-L1-positive advanced NSCLC.
The study included 264 patients age 75 years or older (range, 75-90) and 2,292 patients younger than 75 years. All patients had PD-L1 tumor proportion scores (TPS) of 1% or higher, and half (n = 132) of the elderly group had TPS scores of 50% or higher.
In KEYNOTE-010, patients received either pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or docetaxel as second-line or later treatment. In KEYNOTE-024 and KEYNOTE-042, patients received pembrolizumab 200 mg every 3 weeks or platinum-based chemotherapy as first-line therapy.
Regardless of the line of treatment, results showed longer OS with pembrolizumab vs. chemotherapy in patients with a PD-L1 TPS of 1% or higher (HR = 0.76; 95% CI, 0.56-1.02) and in patients with a PD-L1 TPS of 50% or higher (HR = 0.4; 95% CI, 0.25-0.64).
Pembrolizumab also conferred an OS benefit compared with chemotherapy as first-line treatment for patients with a PD-L1 TPS of 50% or higher (HR = 0.41; 95% CI, 0.23-0.73).
Elderly and younger patients had similar 1-year OS rates with pembrolizumab, including for those with a PD-L1 TPS of 1% or higher (53.7% vs. 54.9%) and for those with a PD-L1 TPS of 50% or higher (61.7% for both).
A smaller proportion of elderly patients who received pembrolizumab vs. chemotherapy demonstrated treatment-related adverse events (68% vs. 94%), including grade 3 to grade 5 events (24% vs. 61%). However, pembrolizumab appeared associated with a higher rate of immune-mediated adverse events and infusion reactions among elderly patients (25% vs. 7%) and younger patients (25% vs. 6%)..
“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,” lead study author Kaname Nosaki, MD, of National Hospital Organization Kyushu Cancer Center in Fukuoka, Japan, said in a press release. “Our data support the use of pembrolizumab monotherapy in elderly patients with advanced PD-L1-expressing NSCLC.”
In the second study, researchers evaluated 98 patients (mean age, 62 years; range, 41-85; 73% men) with advanced NSCLC who received anti-PD-1 and anti-PD-L1 immunotherapy agents at Hospital Universitario Ramon y Cajal in Madrid between 2014 and 2018. Nearly two-thirds of patients (64.3%) had adenocarcinoma (41% KRAS mutated), and 25.5% had squamous disease. Half had a known PD-L1 status.
Sixty-one percent of patients received immunotherapy as second-line treatment and 24.5% received it as third-line or later treatment. Fifty-two percent of the patients received nivolumab (Opdivo, Bristol-Myers Squibb).
Results showed OS of 5.5 months in elderly patients (age 70 years or older) vs. 13 months in patients younger than 70 years (HR = 3.86; 95% CI, 2.07-7.21).
PFS also was significantly shorter in elderly patients compared with younger patients (1.8 months vs. 3.6 months; HR = 2.1; 95% CI, 1.18-3.74).
The overall response rate among all patients was 32.7% (partial response, 28%; complete response, 5%).
Immune-related adverse events occurred in 30.6% of patients. Results showed no significant differences in the rate of adverse events between elderly and younger patients (P = 0.535).
“Our results suggest that elderly patients could have worse survival outcomes with immunotherapy than younger patients, without differences in toxicity,” Elena Corral de la Fuente, MD, and Arantzazu Barquin Garcia, MD, of the Hospital Universitario Ramon y Cajal in Madrid, Spain, said in a joint statement in the press release. “Prospective randomized clinical trials and more real-world data are needed to answer remaining questions on the use of immunotherapy in elderly patients.” – by John DeRosier
Nosaki K, et al. Abstract 103O. Presented at: European Lung Cancer Congress; April 10-13, 2019; Geneva.
De la Fuente EC, et al. Abstract 169P_PR. Presented at: European Lung Cancer Congress; April 10-13, 2019; Geneva.
Disclosures: Nosaki reports honoraria from AstraZeneca, Chugai Pharmaceutical, Eli Lilly and Merck, and research funding from Merck. De la Fuente and Barquin Garcia report no relevant financial disclosures. Please see the abstracts for all other authors’ relevant financial disclosures.