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Prostate Cancer Lab #5: Drug Combinations Promise Precision (CureMatch)

Meeting Summary

At our last meeting on April 20, Ally Perlina, Chief Science Officer at CureMatch, presented combinations of approved drugs that are the best fit for advanced prostate cancer patient Brian McCloskey based on his cancer’s unique molecular profile. CureMatch is a San Diego-based company that takes biomarkers identified by most any diagnostic sequencing test and matches them with approved drugs in combinations. Their distinctive value is using multiple drugs in combination to achieve a better fit with the unique characteristics of a patient’s cancer and therefore better patient outcomes.

The CureMatch system starts with input from a patient’s molecular profile, derived from DNA and/or RNA sequencing of a patient’s tumor tissue or liquid biopsy sample. The test will identify biomarkers or variants of interest (variants from normal cells, potential drivers of the cancer), usually 4 to 6. Not all biomarkers or variants go into the algorithm. Some may be rejected because they are not pathogenic (don’t drive the disease), and some because there are no therapies targeting that biomarker. The physician has latitude to include or exclude biomarkers or treatment options due to any reason, such as medical history. For example, Brian had pembrolizumab, so he might decide to remove it as a treatment option. Then CureMatch analyzes the patient’s selected biomarkers against the roughly 300 drugs that the FDA has approved in combinations of 3, 2, or 1 drugs. They do not include clinical trials in their recommendations. For example, Brian has a variant (B7-H3/CD276) which has several clinical trials targeting this pathway, but it would not be included in a CureMatch recommendation because there are no approved drugs for it yet. Off-label uses of drugs (drugs that have been approved but for a different indication) are included in the treatment combinations.

The roughly 4.5 million possible combinations of the roughly 300 approved drugs are then scored on the extent to which they address the patient’s selected biomarkers. If a drug combination addresses 4 of 6 biomarkers, the score is 67%, 3 of 6 would be 50%, and 2 of 6 would be 33%. The drug combinations are ranked on their scores, with explanations and links to support the choices. For example, Brian had 6 actionable markers, 16 on compendia drugs, 54 matching drugs, and 24,857 relevant combinations. CureMatch’s top option, with a score of 32%, was a 3-drug combination of apalutamide (FDA approved, AR target), olaparib (FDA approved, FANCA target via PARP-1, PARP-2), and trametinib (off-label, BRAF target via MAP2K1, MAP2K2, and MAP2K2 target).

As Emma Shtivelman, an experienced PhD molecular biologist and Chief Scientist at Cancer Commons summed up,… someone like me looks more for clinical trials rather than off-label treatment options. And when I look for clinical trials, I keep in mind the previous treatments… CureMatch has this assumption that a physician will be able to prescribe off-label combinations of two or three drugs. This happens rarely, even with the best specification. I know two patients who had recommendations from CureMatch and their physicians worked with the recommendations, and it worked great. But it’s an exception… It’s unfortunate and very frustrating.”

Advanced Prostate Cancer Patient Panel Report

Brian McCloskey shared highlights from a meeting of advanced prostate cancer patients who have registered with the Prostate Cancer Lab community.

Four themes emerged that they would like to see if they could change one thing about their care:

  • Better physician-patient communication: Providing patients with simple language they can use to understand their disease and treatment options.
  • Better diagnostics for personalizing treatments: Tailoring treatments uniquely to the profile of each individual.
  • Medical guide partner: Finding a trusted medical advisor who will be an expert partner on the journey.
  • Access to experts: Achieving a high quality of care in rural locations.
 

Requests

  • Do you have any feedback on the CureMatch presentation? Would you recommend their approach to a friend or family member?
  • Do you know anyone who would be a good candidate to serve on our Prostate Cancer Lab patient board? The candidate should be very active in wanting to learn more about his advanced prostate cancer and treatment options. Read more and register here.

Meeting Recording

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