“The bottom line is that if you have a higher matching score, which is you have more mutations with drugs targeted to them, you get significantly improved progression free survival, disease control rate, and overall survival. Patients did better with a more matched therapy.” – Dr. Mina Nikanjam
“We slowly titrate the drugs up to a level where we’re treating the cancer well, and the patients are not getting sick. If you start too low, it doesn’t work. If you start too high, the patient gets sick, and you have to stop therapy. It’s a fine line, starting at the right level and going up slowly so the patient’s not getting sick.” – Dr. Mina Nikanjam
Advanced cancer patients want access to precision medicine, which means novel combinations of therapies unique to them. However, an objection to a novel (“off label”) treatment or drug combination can be not knowing about the potential toxicity impact on the patient. Custom dosing offers a partial solution to the problem of novel therapy combinations.
Mina Nikanjam, MD, PhD, medical oncologist at UC San Diego Health, is uniquely positioned to describe help that she has provided to patients with dosing for drug combinations, the cumulative clinical trial evidence that came out of a study (the I-PREDICT study) that shows that combinations are better than single agents, and some strategic principles that guide how you should think about dosing in the case of drug combinations. Dr. Nikanjam also has lots of experience in working with a variety of treating physicians on delivering personalized drug combinations.
How does a personalized dosing strategy work for “off label” treatments, e.g., drug combinations?
Here are the findings and some general principles that came out of the research Dr. Nikanjam did with Dr. Razelle Kurzrock on dosing for drug combinations:
- Toxicity: Some classes of drugs, e.g., mTOR, PARP, and HDAC inhibitors, tend to be a bit more toxic. Antibodies are less toxic than the small molecule inhibitors and cytotoxic chemotherapy. If you have an overlapping target for a small molecule, this can give you increased toxicity. For example, if you have two drugs targeting EGFR, that tends to be more toxic than going after separate targets.
- Dosing principles: For a small molecule, start most at 50% dose. Many of the antibodies, because they’re better tolerated, can start at full dose. With mTOR, PARP, and HDAC inhibitors, be very cautious and often start at 25% of the standard dose, or even more.
- Dosing process: See the patients every week in the clinic, get labs, and see how they’re doing. Slowly titrate the drugs up to a level where the cancer is being treated well, and the patients are not getting sick. If you start too low, it doesn’t work. If you start too high, the patient gets sick, and you have to stop therapy. It’s a fine line, starting at the right level and going up slowly so the patient’s not getting sick. And if you continue therapy, you’re also treating the cancer well.
How should advanced cancer patients approach the new testing and treatment possibilities enabled by precision medicine in their specific cases?
While precision medicine is advancing and evolving at a rapid pace, it is not considered a curative treatment at this time; rather, it is a disease management treatment. If a patient has a curative intent treatment still on the table, they should pursue that first.
How can patients access personalized treatment options?
Patients sometimes have a challenge in getting access to the drugs that are indicated in a drug matching process. A lot of these drugs are “off label” – in combinations that haven’t been in clinical trials. If you submit these drug combinations through insurance, they tend to decline it.
To get access, patients and caregivers can:
- Rely on the medication acquisition teams at hospitals.
- Find an oncologist willing to prescribe the drug combination.
Is electing to have surgery to harvest tissue for testing worthwhile?
While getting more tissue to run tests is always better, there are reasons to put it off:
- If a patient already has a lot of information from testing, such as whole exome and RNA sequencing, and has identified actionable markers and curative options, they should exhaust those first.
- If the cancer recurs, tissue from the recurrence spot will be much more valuable since the cancer may have mutated from the original site.
- Testing in years to come will be much more informative than today, so it could be more informative to test later, if needed. However, patients who don’t have time to wait for future tests can start a treatment option with the diagnostic information they have today and include results from additional tests as they become ready. There is a lot of technology available, such as spatial analysis and proteomics, and we are still figuring out how to make best use of it in the clinic.
What can active and engaged patients do to help accelerate precision medicine?
Be proactive promoting to other patients about how important matched therapy is. The more people are excited, the more grants will get funded for research helping patients
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