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Precision Medicine Tested for Combination Cancer Therapies

Cancer magnified

(PDPics, Pixabay)

23 Apr. 2019. Results from a clinical trial show precision medicine, where the genomic nature of tumors guides the choice of treatment, can identify a combination of cancer therapies with better outcomes for patients. Findings from the study, headed by a team at University California in San Diego, appear in yesterday’s issue of the journal Nature Medicine.

Researchers led by cancer specialists Razelle Kurzrock and Jason Sicklick are seeking to apply precision medicine to patients for whom a combination of treatments are more appropriate than a single therapy. Up to now, nearly all precision medicine studies identified a single treatment that meets the genomic profile of patients’ tumors. The authors point out, however, that a single-therapy approach is hampered by low matching rates, usually between 5 and 10 percent. The low matches, say the researchers, may be due to limits on the genes and mutations in the screening panels, restrictive algorithms matching the mutations to drugs, unavailability of matching drugs identified by the screening, or deterioration in the patient before the treatment can be administered.

Safety issues up to now kept many cancer specialists from trying combination therapies in precision medicine. “Personalized, multi-drug therapies have not been used as standard treatment,” says Sicklick in a university statement, “because there are concerns about the safety of administering drug combinations that have not been previously studied together.”

The team proposed improving the matching rates by screening for a combinations of therapies, instead of identifying a single drug. The screening method also was expanded to find multiple variations associated with cancer in the tumor genomes. The company Foundation Medicine in Cambridge, Massachusetts conducted genomic screenings of 149 patients enrolled in a larger precision medicine clinical trial. Foundation Medicine performs high-throughput genomic sequencing of 324 genes most associated with tumor growth, and evaluates related indicators to determine possible benefits of specific kinds of treatments, such as immunotherapies. As reported by Science & Enterprise in December 2017, FDA approved the company’s FoundationOne CDx tests for some solid tumor cancers, with mutations matched to 15 treatment options.

The 149 patients that enrolled all had solid tumor cancers that metastasized, or spread in their bodies, and were not responding to conventional treatments. Of the 149 original participants, the cancer in 66 patients advanced too far for treatment. Of the remaining 83 participants, only 10 were found without any matches, leaving 73 participants, or 49 percent of the original group, where the team found a match between tumor genomic profile and therapies.

Of the patients highly matched to their combination therapies– half or more of their mutations matched to available therapies — 50 percent responded to the treatments, with longer progression-free and overall survival times. Of participants with lower matching scores, only 22 percent responded to their treatments. The treatments in the combinations included targeted drugs, hormone therapies, immunotherapies, and chemotherapies.

“Having 50 percent of patients with heavily pretreated disease responding when highly matched speaks to the importance of personalized, precision medicine combination approaches,” notes Kurzrock. “Our next step is to determine if we can increase the benefit rate further if this strategy is instituted earlier in the course of the disease.”

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