Prostate Cancer Lab #15: Feedback on My 17 Treatment Options? (Brian McCloskey)

Advanced cancer patient Brian McCloskey shared the 17 treatment options that have been identified for him by various sources, including Cancer Commons/xCures, CureMatch, and Massive Bio, and solicited input on the complex decision he is facing in prioritizing among them. Brian had reviewed these options with his oncologist, Dr. Rana McKay, and he shared her opinions.

Rising to the top of his shortlist from the 17 options were four preferred treatments:

• An androgen receptor (AR) degrader (ARV-766) which destroys AR expression, not just inhibits it, available through a clinical trial from Arvinas identified by Massive Bio. (Prostate cancer is driven by the hormone androgen. Many treatments for prostate cancer inhibit androgen production. This drug attacks androgen reception.) Brian’s genomic analysis shows high AR expression.
• An Antibody Drug Conjugate (ADC) targeting B7-H3. This is available through a Daichi clinical trial. Brian’s primary and met tumor RNA seq analysis (done by Rick Stanton with Tempus data) shows very high expressions of B7-H3. An ADC is a monoclonal antibody chemically linked to a drug. The monoclonal antibody binds to specific proteins or receptors found on the cancer cells, and spares healthy cells.
• Pluvicto, the newly approved radioactive nanoparticle drug that binds to Prostate Specific Membrane Antigen. Rana McKay has seen very strong responses to this drug among her patients. There are challenges with access right now.
• Cabazitaxel, a standard of care drug for men with metastatic castration-resistant prostate cancer. It is a type of chemotherapy called a microtubule inhibitor.

Bipolar androgen therapy, a treatment tailored for a patient who has become “castration-resistant” (deprived of androgen through drugs, yet PSA is rising), is also something Brian is considering. It has been very effective for his friend, advanced prostate cancer patient Bryce Olson.

Emma Shtivelman, PhD, Cancer Commons Chief Scientist, a molecular biologist who has much experience in making treatment recommendations, weighed in with her opinions about Brian’s treatment strategy and tactics. She was attracted to pathways that are different from the androgen receptor pathway, which has been drugged for Brian several ways already. She feels that CAR-T is a potentially valuable treatment option, as is PSMA targeting (Pluvicto), but that they are farther off in Brian’s future. Therefore, she favored the Antibody Drug Conjugate attacking B7-H3. She also liked the trial sponsor, Daichi, which is a leader in the field of making good Antibody Drug Conjugates.

The drug combination options were a concern for Rana McKay, due to toxicity and quality of life risks. Brad Power and Saed Sayad recommended lower dosages for each of the drugs in a drug combination. Brian wanted to see evidence for lower dosages. Brad said that is in the domain of experts (not clinical trial evidence), and suggested we tap a dosing expert.

Requests

• Do you know anyone who is an expert on dosing, especially as a way to reduce toxicity concerns in drug combinations?
• Would you like to join a group to talk about how we could create or find protocols (observational trials) that willing physicians could put their patients in to benefit them in real time, as opposed to 20 years from now, after you collect enough data?