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ASCO GU 2020: Dr. Taplin Highlights Ongoing Research in Prostate Cancer

Mary-Ellen Taplin, MD
Published: Thursday, Mar 26, 2020



Mary-Ellen Taplin, MD, chair of the Executive Committee for Clinical Research, director of clinical research at Lank Center for Genitourinary Oncology, and institute physician at Dana-Farber Cancer Institute, as well as professor of medicine at Harvard Medical School, discusses ongoing research in the prostate cancer treatment paradigm that were presented at the 2020 Genitourinary Cancers Symposium.

A randomized phase II trial (NCT02463799) examining sipuleucel-T (Provenge) with or without radium-223 (Xofigo) in patients with asymptomatic bone-metastatic castrate-resistant prostate cancer (mCRPC) showed that the time to radiographic/clinical progression was longer in the sipuleucel-T plus radium-223 arm at a median of 9.3 months versus 3.1 months with sipuleucel-T alone (HR 0.26; 95% CI 0.11–0.61; P= 0.0011). Additionally, the prostate-specific antigen response and the alkaline phosphatase response were also significantly improved with the combination versus sipuleucel-T monotherapy. However, it’s important to remember that this is a very small study, according to Taplin. A larger data set is needed, but these early results appear promising, says Taplin.

Results from a posthoc analysis of the phase III TITAN trial were also presented at the symposium. Results showed that the addition of apalutamide (Erleada) to androgen deprivation therapy (ADT) reduced the risk of second progression or death (PFS2) by 34% versus ADT alone in patients with metastatic castration-sensitive prostate cancer. Notably, the PFS2 benefit was observed regardless of the first subsequent systemic therapy following study treatment. Specifically the hazard ratio for PFS2, which favored the apalutamide arm, was 0.66 (95% CI, 0.50-0.87; P = .0026), indicating effective early intensification of treatment. Furthermore, the benefit of apalutamide plus ADT proved consistent regardless of whether patients received hormonal therapy (HR, 0.684; 95% CI, 0.482-0.971; P = .0326) or taxane therapy (HR, 0.634; 95% CI, 0.456-0.881; P = .0062) as first subsequent treatment. Another 1-2 years of data is needed, but the results are encouraging, says Taplin.

Prostate cancer, according to Taplin, is one of the few cancers where it has not been proven that the combination of systemic therapy with surgery will improve outcomes for patients. The randomized, double-blind, phase III PROTEUS trial (NCT03767244) will be the first large-phase neoadjuvant trial to be done in 12 years in localized high-risk prostate cancer, says Taplin. In the trial, investigators will examine whether the combination of apalutamide plus ADT given before and after radical prostatectomy in patients with high-risk localized or locally advanced prostate cancer will improve pathologic complete response rate and metastasis-free survival more effectively than placebo plus ADT. Patients randomized to apalutamide plus ADT will receive 240 mg of apalutamide daily for 6 cycles before undergoing radical prostatectomy. Meanwhile, patients randomized to the ADT arm will receive placebo in place of apalutamide. This trial could potentially open the door to other research efforts in this space, says Taplin. Excitingly, the trial is accruing much quicker than anticipated and has already proven to be well received by patients and oncologists alike, adds Taplin.

In recent years, the progress made in the understanding of DNA repair alterations and the development of PARP inhibitors has generated excitement in prostate cancer. However, investigators have much more to learn with regard to the patients who are exceptional responders versus nonresponders. Furthermore, although hormone drugs have been around for more than 10 years, investigators are learning how to use these agents earlier on and in various contexts; that work will continue. Perhaps most excitingly, are ongoing drug development efforts and the research exploring new pathways, concludes Taplin.
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Mary-Ellen Taplin, MD, chair of the Executive Committee for Clinical Research, director of clinical research at Lank Center for Genitourinary Oncology, and institute physician at Dana-Farber Cancer Institute, as well as professor of medicine at Harvard Medical School, discusses ongoing research in the prostate cancer treatment paradigm that were presented at the 2020 Genitourinary Cancers Symposium.

A randomized phase II trial (NCT02463799) examining sipuleucel-T (Provenge) with or without radium-223 (Xofigo) in patients with asymptomatic bone-metastatic castrate-resistant prostate cancer (mCRPC) showed that the time to radiographic/clinical progression was longer in the sipuleucel-T plus radium-223 arm at a median of 9.3 months versus 3.1 months with sipuleucel-T alone (HR 0.26; 95% CI 0.11–0.61; P= 0.0011). Additionally, the prostate-specific antigen response and the alkaline phosphatase response were also significantly improved with the combination versus sipuleucel-T monotherapy. However, it’s important to remember that this is a very small study, according to Taplin. A larger data set is needed, but these early results appear promising, says Taplin.

Results from a posthoc analysis of the phase III TITAN trial were also presented at the symposium. Results showed that the addition of apalutamide (Erleada) to androgen deprivation therapy (ADT) reduced the risk of second progression or death (PFS2) by 34% versus ADT alone in patients with metastatic castration-sensitive prostate cancer. Notably, the PFS2 benefit was observed regardless of the first subsequent systemic therapy following study treatment. Specifically the hazard ratio for PFS2, which favored the apalutamide arm, was 0.66 (95% CI, 0.50-0.87; P = .0026), indicating effective early intensification of treatment. Furthermore, the benefit of apalutamide plus ADT proved consistent regardless of whether patients received hormonal therapy (HR, 0.684; 95% CI, 0.482-0.971; P = .0326) or taxane therapy (HR, 0.634; 95% CI, 0.456-0.881; P = .0062) as first subsequent treatment. Another 1-2 years of data is needed, but the results are encouraging, says Taplin.

Prostate cancer, according to Taplin, is one of the few cancers where it has not been proven that the combination of systemic therapy with surgery will improve outcomes for patients. The randomized, double-blind, phase III PROTEUS trial (NCT03767244) will be the first large-phase neoadjuvant trial to be done in 12 years in localized high-risk prostate cancer, says Taplin. In the trial, investigators will examine whether the combination of apalutamide plus ADT given before and after radical prostatectomy in patients with high-risk localized or locally advanced prostate cancer will improve pathologic complete response rate and metastasis-free survival more effectively than placebo plus ADT. Patients randomized to apalutamide plus ADT will receive 240 mg of apalutamide daily for 6 cycles before undergoing radical prostatectomy. Meanwhile, patients randomized to the ADT arm will receive placebo in place of apalutamide. This trial could potentially open the door to other research efforts in this space, says Taplin. Excitingly, the trial is accruing much quicker than anticipated and has already proven to be well received by patients and oncologists alike, adds Taplin.

In recent years, the progress made in the understanding of DNA repair alterations and the development of PARP inhibitors has generated excitement in prostate cancer. However, investigators have much more to learn with regard to the patients who are exceptional responders versus nonresponders. Furthermore, although hormone drugs have been around for more than 10 years, investigators are learning how to use these agents earlier on and in various contexts; that work will continue. Perhaps most excitingly, are ongoing drug development efforts and the research exploring new pathways, concludes Taplin.
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