New medications and treatment protocols are improving survival rates for patients whose prostate cancer recurs after prostatectomy. As part of this advance, ongoing clinical trials at Duke are exploring how aggressively to implement salvage treatment of biochemical recurrence and offering patients opportunities to test new treatments.
The current approach to salvage therapy includes six to 24 months of androgen deprivation therapy (ADT)—with an agent such as leuprolide acetate or the first-generation androgen receptor antagonist bicalutamide—coupled with radiation therapy after a patient’s incontinence resolves (three to six months after prostatectomy).
Clinical trials have shown that adding a second-generation androgen-receptor antagonist—such as enzalutamide, apalutamide, and darolutamide—can delay the time to metastasis and prostate-specific antigen (PSA) progression in castration resistant prostate cancer, says Tian Zhang, MD, a Duke medical oncologist.
For example, Duke’s STREAM trial enrolled patients who had experienced a PSA recurrence within four years of prostatectomy and had high-risk disease. The patients were treated with enzalutamide added to ADT, and then underwent salvage radiation. “The three-year PSA-progression-free survival was 53%,” Zhang says, an improvement over the 45% rate using bicalutamide and radiation alone.
Zhang and her colleagues are now exploring how best to use these new agents in conjunction with chemotherapy. Two clinical trials are currently enrolling patients.
The STARTAR trial (NCT03311555) is open to patients with PSA recurrence less than four years after radical prostatectomy who have Gleason scores of 8 to 10 or a Gleason 7 score with pT3 disease, positive nodes, or positive margins. The treatment includes nine months of ADT and apalutamide, salvage radiation, and an add-on of six cycles of docetaxel. Docetaxel, a cytotoxic chemotherapy agent that inhibits microtubule formation, has been shown to prolong survival in men with metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer.
“The STARTAR trial is a test of the efficacy of moving chemotherapy up front to see whether we can get rid of microscopic disease in this setting and prevent the time to metastasis,” Zhang says. “The endpoint is three-year PSA-progression-free survival rates, with a hope of improving the STREAM trial’s 53% survival rate to 75%.” In addition to Duke, STARTAR is enrolling patients at the Wake Forest and Cornell university health systems.
The NRG GU-002 trial (NCT03070886) is accepting similar patients (but without node-positive disease). It features six months of ADT and bicalutamide as well as radiation therapy and will then have two segments to compare six cycles with and without docetaxel.
“Our goal is to prevent recurrence and to keep patients’ tumor volume and PSAs low,” Zhang says. “We might find that docetaxel adds a lot of toxicity and not a lot of clinically meaningful benefits, and that is why we do the trials. We think an aggressive approach upfront can ultimately prevent prostate cancer recurrence and allow people to live longer.”
To enroll a patient in one of these clinical trials at Duke, contact Julia Rasmussen at 919-681-1030 or email@example.com.