The old model of cancer treatments consisted of administering nonspecific cytotoxic therapies to various cancer patients. Now, cancer treatment has evolved to include agents that target a patient's genome and immune system, resulting in better patient outcomes. This 'precision medicine' approach individualizes treatment depending on each patient's unique tumor. Researchers discovered that using precision medicine to select combination treatments that target more than one genomic alteration is effective in treating patients with refractory malignancies.
In this investigation, published in Nature Medicine, 83 patients with refractory metastatic cancers had their tumor tissue genome profiled by Foundation Medicine's FoundationOne genomic analysis. Seventy-three of those patients received personalized precision therapy containing molecularly matched treatments. Molecular matching consists of analyzing a patient's tumor tissue genome using next-generation sequencing to determine presence of programmed death-ligand 1, immunohistochemistry, tumor mutational burden, microsatellite instability status, and blood-derived circulating tumor DNA. The treatment selected for the patient depends on these results. Because no two molecular profiles were identical, most treatment regimens varied. For the other 10 patients, 'unmatched' treatments were administered, most often due to health care provider and patient preference and drug toxicities.
After a median follow-up of 10.8 months, patients who received a molecularly matched treatment compared with those who received 'unmatched' treatments attained an increased disease control rate (50% vs 22.4%). In addition, matched-treated patients achieved higher progression-free survival (6.5 vs 3.1 months) and overall survival (8.5 vs 10.2 months) compared with unmatched patients.
The study authors conclude, "Our findings suggest that the current clinical trial paradigm for precision oncology, which pairs one driver mutation with one drug, may be optimized by treating molecularly complex and heterogenous cancers with combinations of customized agents."
For More Information
Clinicaltrials.gov (2019). Study of molecular profile-related evidence to determine individualized therapy for advanced or poor prognosis cancers (I-PREDICT). NLM Identifier: NCT02534675.
Sicklick JK, Kato S, Okamura R, et al (2019). Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med. [Epub ahead of print] DOI:10.1038/s41591-019-0407-5
Image Courtesy of National Cancer Institute