In Melanoma, Older Adults Could Benefit More From Treatment With PD-1 Inhibitors

On the heels of some stunning results on checkpoint blockade molecules presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting — which demonstrated that pembrolizumab led to better overall survival rates compared with platinum-based chemotherapy in previously untreated patients with advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR or ALK mutations and PD-L1 tumor proportion score (TPS) greater than or equal to 1% — comes new data on the drug’s ability to treat certain populations of patients with melanoma, this time published in Clinical Cancer Research.^1,2

The observational study, which examined samples from 538 patients with primary or metastatic disease, found that patient age was a determinant of a positive outcome when considering treatment with the anti-PD-1 pembrolizumab. There were statistically significant age-mediated differences in the intratumoral immune response to this immunomodulator (P = .02).

Previous findings have shown that as patients with melanoma age, their response to targeted therapies such as BRAF inhibitors wanes, and the probability of cancer metastasis increases.³ But with PD-1 inhibitors, researchers from The Wistar Institute in Philadelphia, Pennsylvania, observed the opposite result — patients older than 62 years responded better to treatment with these type of immunotherapies.

While 50% of patients with melanoma younger than 62 years saw no benefit from treatment with pembrolizumab, 37% of patients aged 62 years or older failed to respond to the drug. And with each decade of life, there was a significant decrease in the chance that a patient’s disease progressed after treatment with the immunotherapy.

“This was really a surprise to us because we expected the loss of immune activity that we see in older people to play a role in driving resistance,” lead researcher Ashani T. Weeraratna, PhD, the Ira Brind professor and co-program leader of the Immunology, Microenvironment and Metastasis Program at The Wistar Institute, told Cancer Therapy Advisor in an email. “Instead, we saw the opposite [result].”