Two studies to be reported at ELCC 2019 provide new insights on the efficacy and safety of immunotherapy in elderly patients with advanced non-small-cell lung cancer (NSCLC), where information has previously been lacking despite being the age group most commonly affected.

Immunotherapy with drugs that target immune pathways to enhance the body's ability to recognise and destroy tumour cells is emerging as an effective treatment option for patients with advanced NSCLC.

Although around half of all people newly diagnosed with NSCLC are elderly there is currently limited evidence on the efficacy and safety of immunotherapy in this age group because they have been under-represented 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.

Both studies have been published in the journal Annals of Oncology.

Real-life study suggests shorter overall survival with immunotherapy in the elderly

A retrospective study of patients with advanced NSCLC treated with immunotherapy in real-life clinical practice suggested that elderly patients (greater than equal to 70 years) may have shorter overall survival than younger patients but demonstrated that toxicity was similar.

Researchers retrospectively reviewed all patients with advanced NSCLC treated with immunotherapy agents at Hospital Universitario Ramon y Cajal in Madrid, Spain, between 2014 and 2018.

Just over one in four (27 patients; 27.5 percent) of the 98 patients treated with immunotherapy agents over this four-year period were aged 70 years or older.

PD-L1 status was known in 50 percent of patients.

Overall survival in these elderly patients was significantly shorter than in patients younger than 70 years of age (median 5.5 months vs 13 months, hazard ratio [HR] 3.86, 95% confidence interval [CI] 2.073-7.214, p<0.0001).

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=0.012).

Considering toxicity, there were no statistically significant differences in immune-related adverse events between elderly and younger patients (p=0.535).

The study shows that immunotherapy was administered mainly as second-line treatment (61 percent of patients) or third-line or later (24.5 percent) across the entire group of 98 patients of all ages.

Just over half (52 percent) were treated with nivolumab.

"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 Elena Corral de la Fuente and Arantzazu Barquin Garcia, from the Hospital Universitario Ramon y Cajal, Madrid, Spain.

They acknowledged that the study was limited by being an observational retrospective analysis with a small sample size.

They suggested, "Prospective randomised clinical trials and more real-world data are needed to answer remaining questions on the use of immunotherapy in elderly patients."

Pooled analysis demonstrates improved overall survival with immunotherapy

A second study pooling data from three randomised trials shows significantly improved overall survival in elderly patients with advanced NSCLC treated with the immunotherapy agent pembrolizumab compared to those given chemotherapy.

The study compared the efficacy and safety results for 264 elderly patients aged greater than or equal to 75 years in the three trials with results for 2292 participants younger than 75 years.

All of the patients had PD-L1 tumour proportion scores (PD-L1 TPS) of 1 percent or higher and half of the elderly group in this analysis had scores of at least 50 percent. 

Results show significantly improved overall survival in elderly patients with PD-L1 tumours scores greater than or equal to 1 percent treated with pembrolizumab compared to those treated with chemotherapy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.56-1.02).

The improvement in overall survival with pembrolizumab compared to chemotherapy was even greater in patients with PD-L1 tumour scores greater than or equal to 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 percent vs 54.9 percent in PD-L1 TPS greater than or equal to 1 percent and 61.7 percent vs 61.7 percent in PD-L1 TPS greater than or equal to 50 percent).

Fewer elderly patients treated with pembrolizumab had treatment-related adverse events compared to those treated with chemotherapy (68 percent vs 94 percent).

Grade 3-5 treatment-related adverse events in elderly patients were also less common with pembrolizumab compared to chemotherapy (24 percent vs 61 percent). Common treatment-related adverse events with pembrolizumab in elderly patients were fatigue (17.4 percent), decreased appetite (12.8 percent) and pruritus (12.8 percent).

Immune-mediated adverse events and infusion reactions were more frequent with pembrolizumab vs chemotherapy in the elderly group of patients (25 percent vs 7 percent) but showed no difference compared to younger patients treated with pembrolizumab (25 percent).

"In elderly patients with advanced NSCLC with PD-L1-positive tumours, pembrolizumab monotherapy improved overall survival over chemotherapy, together with a more favourable safety profile," said lead author Kaname Nosaki, from the National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

He added, "Our data support the use of pembrolizumab monotherapy in elderly patients (greater than or equal to 75 years) with advanced PD-L1- expressing NSCLC."

Considering potential limitations, 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.

Commenting on the studies, Marina Garassino, Chief of Thoracic Oncology at the Istituto Nazionale dei Tumori, Milan, Italy, said, "The pooled analysis of clinical trials showed no difference in the efficacy and safety of immunotherapy in the elderly compared to younger patients. But the real-world study is an alarm bell potentially suggesting lower efficacy with immunotherapy in elderly patients despite no difference in adverse events."

In terms of limitations, she noted that PL-1 expression was known in only 50 percent 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 randomised trials," she mentioned, but added that elderly patients are generally under-represented in clinical trials.

Looking to the future, Garassino concluded, "We need larger, prospective trials or larger real-world studies to gain a more detailed view on the efficacy and safety of immunotherapy in elderly patients with NSCLC."

Source: European Society for Medical Oncology