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

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Patient age should play a role in drug development strategies for melanoma, researchers of a new study say.
Patient age should play a role in drug development strategies for melanoma, researchers of a new study say.

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).

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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].”

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