Maha H.A. Hussain, MD, FACP, FASCO, and Mary-Ellen Taplin, MD, sit down with 

® to travel the road that led them to specialize in genitourinary oncology, the challenges they experienced as females in the field, and advice they would give to not only female oncologists starting out in their career, but to their younger selves with the knowledge that they have now. 

Hussain is the Genevieve Teuton Professor of Medicine in the Division of Hematology Oncology, Department of Medicine, and the Deputy Director at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine. 

Meanwhile, Taplin is the director of Clinical Research, Lank Center for Genitourinary Oncology and institute physician at Dana-Farber Cancer Institute, and professor of medicine at Harvard Medical School. 

Both leaders in oncology share their life lessons as women practicing genitourinary cancers, and give intel on how society has evolved in relation to gender equality in the oncology workforce throughout their careers. 

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Maha H.A. Hussain, MD, and Mary-Ellen Taplin, MD, sit down with OncLive® to travel the road that led them to specialize in genitourinary oncology, the challenges they experienced as a female in the field, and advice they would give to not only other rising female oncologists, but to their younger selves knowing what they know now.

Hussain and Taplin Talk Gender-Specific Struggles, Career Lessons in GU Oncology

Mary Ellen Taplin, MD, chair, executive committee for Clinical Research, director of Clinical Research, Lank Center for Genitourinary Oncology, institute physician, Dana-Farber Cancer Institute, associate professor of Medicine, Harvard Medical School, discusses the ongoing ARMOR 3-SV trial for patients with metastatic castration-resistant prostate cancer (mCRPC).

Galeterone is an agent in development for this patient population, Taplin explains. It has a unique mechanism of action in that in addition to being an androgen receptor antagonist and a CYP17 lyase inhibitor, it also degrades the androgen receptor.

For this trial, patients will be screened for the presence of a blood-biomarker AR-V7. Patients who are AR-V7—positive and enrolled on the study will be randomized to receive galeterone or enzalutamide (Xtandi), with a primary endpoint of radiographic progression-free survival.

Dr. Taplin on ARMOR 3-SV Trial for Patients with mCRPC

Mary-Ellen Taplin, MD, associate professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute, discusses the unique mechanism of action (MOA) for the androgen receptor antagonist enzalutamide (Xtandi; MDV3100), which was recently approved by the FDA for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel.

The mechanism of action for the agent enzalumatide makes it a fantastic antiandrogen and sets it apart from older agents such as bicalutamide and nilutamide, explains Taplin. The agent is able to inhibit androgen receptor nuclear translocation rather than competing with androgen in the cytoplasm. Blocking entry into the nucleus prevents gene transcription and the activation of growth factors. Taplin believes this unique MOA is likely the reason that enzalutamide is efficacious in patients with mCRPC following chemotherapy.

The optimal way to sequence this agents is an important question that still needs answered. As a result, researchers are currently examining the administration of enzalutamide in early-stage prostate cancer and combination strategies.

Mary-Ellen Taplin, MD, from the Dana-Farber Cancer Institute, discusses unique mechanism of action of enzalutamide in metastatic castration-resistant prostate cancer.

Dr. Taplin on the Mechanism of Action of Enzalutamide

Mary-Ellen Taplin, MD, associate professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute, describes the mechanism of action for the oral androgen biosynthesis inhibitor abiraterone acetate (Zytiga), which is approved for treating men with castration-resistant prostate cancer.

	The agent abiraterone acetate prevents testosterone production through a mechanism of action that is unique from previous androgen deprivation therapies such as leuprolide and Zoladex. The agent inhibits the CYP17A1 enzyme, a rate-limiting enzyme implicated in androgen biosynthesis that is created primarily by the testicles but also within the adrenal glands and the prostate cancer itself. Blocking this enzyme prevents the conversion of pregnenolone and progesterone into testosterone precursors, such as dehydroepiandrosterone (DHEA) and androstenedione.

	This mechanism of action establishes a more complete inhibition of circulating testosterone. Abiraterone acetate is unique in blocking the adrenal glands and prostatic testosterone production. Other agents only block production at the level of the testicles.

Dr. Mary-Ellen Taplin, from the Dana-Farber Cancer Institute, on Abiraterone Acetate's Mechanism of Action


Dr. Taplin on Abiraterone Acetate's Mechanism of Action

Mary-Ellen Taplin, MD, associate professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute, explains the rationale behind the recent study examining the neoadjuvant administration of abiraterone acetate (Zytiga) in combination with the LHRH analog leuprolide acetate, for patients with localized high-risk prostate cancer.

Taplin explains that several large studies were conducted in the 90's investigating the use of LHRH analogs with or without an antiandrogen therapy before prostatectomy. These trials did not show any additional benefits for the combination, causing the approach to be abandoned.

At the time, the most commonly used androgen deprivation therapy (ADT) was flutamide; however, the recent discovery of more potent ADTs, such as abiraterone acetate and enzalutamide (formally MDV3100), has called for the reinvestigation of the neoadjuvant combination of an LHRH analog and ADT, Taplin states.

The overarching theory behind the reinvestigation of the concept is that as therapies for cancer become more potent it may become necessary to reexamine treatment approaches that were previously thought to be ineffective.

Dr. Mary-Ellen Taplin, from the Dana-Farber Cancer Institute, on Neoadjuvant ADT Plus Hormonal Therapy for Prostate Cancer.


Dr. Taplin on Neoadjuvant ADT Plus Hormonal Therapy

Mary-Ellen Taplin, MD, associate professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute, discusses a randomized phase II trial that administered abiraterone acetate (Zytiga) in combination with the hormonal therapy leuprolide acetate before prostatectomy for men with localized high-risk prostate cancer (LHRPC).

The trial randomized 58 men into two groups that both received 24 weeks of leuprolide acetate and either 12 or 24 weeks of abiraterone acetate, which is indicated to be given with prednisone. The primary endpoint of the trial was to assess the hormone levels in the excised tissue following prostatectomy. The secondary endpoint examined the amount of tumor tissue left, following surgery.

Traditionally, patients receiving leuprolide acetate experience a low level of pathological complete response (pCR), which Taplin defines as no remaining tumor tissue. However, the addition of abiraterone acetate for the full 24 weeks of treatment resulted in a pCR of 10% and a near pCR of 24%.

Taplin notes that the relevance of pCR as an endpoint in prostate cancer has not received evidence-based validation. In other tumors; however, patients who experience a pCR after receiving a neoadjuvant therapy have a higher cure rate at 5 and 10 years but a larger study with a longer follow up is needed to validate this in prostate cancer.

Dr. Mary-Ellen Taplin, from Dana-Farber Cancer Institute, on Neoadjuvant Abiraterone Acetate and Leuprolide Acetate

Mary-Ellen Taplin, MD

Articles

Hussain and Taplin Talk Gender-Specific Struggles, Career Lessons in GU Oncology

Dr. Taplin on ARMOR 3-SV Trial for Patients with mCRPC

Dr. Taplin on the Mechanism of Action of Enzalutamide

Dr. Taplin on Abiraterone Acetate's Mechanism of Action

Dr. Taplin on Neoadjuvant ADT Plus Hormonal Therapy

Dr. Taplin on Neoadjuvant Abiraterone and Leuprolide