Is immunotherapy suitable for elderly patients with advanced NSCLC?
Two studies presented at ELCC 2019 provided contrasting outcomes on the efficacy of immunotherapy in elderly patients with advanced non-small-cell lung cancer (NSCLC).
The first study included 98 patients (mean age 62 years, 73.5 percent male) with advanced NSCLC treated with immunotherapy (either anti-PD1 or anti PD-L1 monotherapy) between 2014 and 2018 at the Hospital Universitario Ramon y Cajal in Madrid, Spain. Of these, 27.5 percent were aged ≥70 years (elderly patients). PD-L1 status was known in 50 percent of patients. [ELCC 2019, abstract 169P_PR]
Adenocarcinoma was the most common diagnosis (64.3 percent), followed by squamous cell carcinoma (25.5 percent). Immunotherapy was most commonly used in the second-line setting (61 percent) with nivolumab the most frequently used drug (52 percent).
The response rate to immunotherapy was 32.7 percent, with 28 percent of patients having a partial response and 5 percent having a complete response. Disease control rate was 55 percent.
Elderly patients had significantly poorer overall survival (OS) compared with patients aged <70 years (median, 5.5 vs 13 months, hazard ratio [HR], 3.86, 95 percent confidence interval [CI], 2.073–7.214; p<0.0001), as well as poorer progression-free survival (PFS; median, 1.8 vs 3.6 months, HR, 2.1, 95 percent CI, 1.181–3.744; p=0.012).
Immune-related adverse events (AEs) occurred at a similar rate between patients aged <70 and ≥70 years (p=0.535).
“Our results suggest that elderly patients could have worse survival outcomes with immunotherapy than younger patients, without differences in terms of toxicity,” said study authors Drs Elena Corral de la Fuente and Arantzazu Barquin Garcia from the Hospital Universitario Ramon y Cajal.
A role for pembrolizumab in elderly advanced NSCLC patients
In the second study, researchers assessed the efficacy and safety of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced NSCLC enrolled in the KEYNOTE-010*, -024**, and -042*** studies.
The 264 patients aged ≥75 years had been randomized to receive pembrolizumab 2 or 10 mg/kg Q3W or docetaxel in second- or later-line setting (KEYNOTE-010) or pembrolizumab 200 mg Q3W or platinum-based chemotherapy in the first-line setting (KEYNOTE-024 and KEYNOTE-042). A total of 132 patients had a tumour proportion score (TPS) of ≥50 percent. [ELCC 2019, abstract 103O_PR]
Patients who received pembrolizumab had superior OS compared with those who received chemotherapy, regardless of treatment setting or patient TPS (HR, 0.76, 95 percent CI, 0.56–1.02 for TPS ≥1 percent and HR, 0.40, 95 percent CI, 0.25–0.64 for TPS ≥50 percent).
The OS improvement was also evident with first-line pembrolizumab vs chemotherapy among patients with TPS ≥50 percent (HR, 0.41, 95 percent CI, 0.23–0.73).
Among pembrolizumab recipients, the 1-year survival rates were comparable between the patients aged ≥75 years and the 2,292 patients aged <75 years enrolled in the three trials (53.7 percent vs 54.9 percent for TPS ≥1 percent and 61.7 percent in each group for TPS ≥50 percent).
Treatment-related AEs (TRAEs) occurred less frequently among pembrolizumab than chemotherapy recipients aged ≥75 years (68 percent vs 94 percent), specifically grade 3–5 AEs (24 percent vs 61 percent) and serious TRAEs (16 percent vs 27 percent). Frequently-experienced TRAEs among elderly pembrolizumab recipients were fatigue (17.4 percent), reduced appetite (12.8 percent), and pruritus (12.8 percent).
In the elderly population, TRAEs led to discontinuation in 11 and 15 percent of pembrolizumab and chemotherapy recipients, respectively, and to death in 1 and 2 percent, respectively. However, immune-mediated AEs and infusion reactions occurred more frequently in elderly pembrolizumab than chemotherapy recipients (25 percent vs 7 percent), though the incidence was comparable with that in younger patients (25 percent vs 6 percent).
“In elderly patients with advanced NSCLC with PD-L1-positive tumours, pembrolizumab monotherapy improved OS over chemotherapy, together with a more favourable safety profile,” said study lead author Dr Kaname Nosaki from the National Hospital Organization Kyushu Cancer Center in Fukuoka, Japan. The results suggest that pembrolizumab as monotherapy could be a suitable treatment option for patients aged ≥75 years with advanced PD-L1‒positive NSCLC, he said.
Moving forward, larger “real-world” trials are vital to provide more information on the safety and efficacy of immunotherapy for NSCLC in the elderly population, said Dr Marina Garassino, chief of thoracic oncology at the Istituto Nazionale dei Tumori, Milan, Italy, who was not affiliated with the studies.
“[While] the pooled analysis of clinical trials showed no difference in the efficacy and safety of immunotherapy in the elderly compared to younger patients … the [first] study is an alarm bell potentially suggesting lower efficacy with immunotherapy in elderly patients despite no difference in AEs,” she noted.