According to new findings from researchers at Yale Cancer Center, higher levels of genetic mutations in tumor biopsies are associated with better clinical results in patients using pembrolizumab (Keytruda) for the treatment of non-small cell lung cancer (NSCLC). The findings were presented today at the European Society for Medical Oncology (ESMO) conference in Barcelona, Spain.
The study suggests that oncologists will soon be able to tailor pembrolizumab to patients with lung cancer who will benefit most from this agent, which is the first checkpoint inhibitor developed and used to treat cancer.
As with all such immunotherapeutic agents, pembrolizumab does not help a subset of patients. For this reason, the oncology community was looking for a test than the therapy could be adapted to use these agents to treat lung cancer and other cancers. "
Dr Roy S. Herbst, general director of medical oncology at Smilow Cancer Hospital and Associate Cancer Center director of translational research at Yale Cancer Center, main author of the study
Herbst collaborated with a team of global researchers to analyze two different clinical studies that tested the use of pembrolizumab as a single therapy in patients with advanced NSCLC. KEYNOTE-010 tested the drug in patients who were previously treated, e.g., Chemotherapy, and previously untreated patients KEYNOTE-042.
Researchers established tissue tumor mutation load (tTMB) in 253 (24%) patients in study KEYNOTE-010 and 793 (62%) of patients included in KEYNOTE-042. TTMB calculations were made by comparing the entire tumor tissue exom sequencing with matched normal DNA.
The association of tTMB with results was evaluated for each study. Researchers found that improvements in overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) in both studies were associated with patients with high tTMB. As with many patients using checkpoint inhibitors, all these patients were classified as having PD-L1 + lung cancer. The designation refers to the PD-1 pathway, which the cancer uses to hide from lethal immune cells. Incorporation of this pathway stops the immune cells from invading cancer cells, allowing cancer to grow and spread. Pembrolizumab blocks this path.
Herbst warns that these results are the result of "exploratory analysis," which was limited to observational subgroups of enrolled patients. "The study gives hope that a proven biomarker can be developed that helps patients who benefit from therapy and who saves patients who do not benefit from potentially toxic treatment," said Herbst.