In this meeting we discussed adaptive therapy, the approach described by Bob Gatenby based on evolutionary and game theory, which rests on four pillars:
- Low dose
- Drug combinations
- Sequencing (not a combination cocktail)
- Mathematical simulation models
Please see the notes from the last meeting (PCL #9) for details on each of these four pillars.
- Drug combinations: Everyone agreed that drug combinations that have a greater fit with identified biomarkers are preferred, but it is difficult to get oncologists to prescribe them. There should be trials that offer a couple of drugs, including investigational drugs. However, even if you want a combination of two approved drugs, they’re considered a new drug (thereby lacking evidence) if you offer them together.
- Sequencing: While sequencing drugs makes sense in theory, there is little evidence to support it from traditional clinical trials, while there is evidence that combination drug cocktails provide better patient outcomes.
- Mathematical simulation models: Saed Sayad pointed out that the models that Bob Gatenby was using were very simple, and that models today are taking more variables into account, such as DNA, mRNA, and proteomics.
- Obstacles: Emma Shtivelman noted that physicians won’t prescribe drug combinations because there are few trials that have tested drug combinations. Even if each of two indicated approved drugs would provide a better outcome, physicians won’t prescribe the combination without clinical trial evidence. There should be clinical trials of drug combinations, including investigational drugs, but the obstacles are almost insurmountable. The combinatorics of a personalized treatment using multiple drugs at multiple doses and different sequencing choices make it nearly impossible to use a randomized clinical trial to derive supporting evidence.
- Do you have any comments on adaptive therapy?
- This adaptive strategy seems intuitive, yet it’s not widely practiced. What are the barriers or objections to it?
- June 1: Tony Letai, MD, PhD, Professor at Dana Farber Cancer Institute, and President, Society for Functional Precision Medicine, on “Functional Precision Medicine for Advanced Cancer”
- June 22: Selin Kurnaz, PhD, Co-founder and CEO, Massive Bio, on “Finding the Best Clinical Trial”