Gomella Discusses Apalutamide Approval and Other Progress in Prostate Cancer


Leonard Gomella, MD, shares his insight on the recent FDA approvals and other ongoing progress in the treatment of patients with prostate cancer.

Leonard G. Gomella, MD

The recent FDA approval of apalutamide (Erleada) for the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC) is a tremendous therapeutic breakthrough, according to Leonard Gomella, MD.

Apalutamide was approved based on the phase III SPARTAN trial, in which the androgen receptor (AR) inhibitor reduced the risk of metastasis or death by 72% in patients with nonmetastatic CRPC.1 The median metastasis-free survival was 40.5 months in the apalutamide arm versus 16.2 months in the placebo arm (HR, 0.28; 95% CI, 0.23-0.35; P <.0001).

Although apalutamide is the first approved treatment in this setting, other agents, such as the AR inhibitor enzalutamide (Xtandi), are showing promise in this population, as well. The phase III PROSPER trial showed that treatment with the combination of enzalutamide and androgen deprivation therapy (ADT) reduced the risk of metastases or death by 71% compared with ADT alone for patients with nonmetastatic CRPC.2

A few weeks prior to the approval of apalutamide, the FDA announced the approval of abiraterone acetate (Zytiga) in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer. This approval was based on findings from the phase III LATITUDE trial, which showed that there was a 38% reduction in the risk of death with the addition of abiraterone acetate and prednisone to ADT compared with ADT alone.3

OncLive: Please provide some insight on the recent approval of apalutamide.

There were some interesting data with enzalutamide out of the 2018 Genitourinary Cancers Symposium. Is there potential for this agent in this population?

There was a recent approval with abiraterone acetate for the treatment of patients with high-risk prostate cancer. Could you provide some insight on this regulatory decision?

Are there any recent developments in immunotherapy for prostate cancer?

What would you like see achieved with immunotherapy in prostate cancer in the next 5 to 10 years?

Is there anything else that you would like to mention about the treatment landscape of prostate cancer?

What work being done at Sidney Kimmel Cancer Center would you like to highlight?

In an interview with OncLive, Leonard Gomella, MD, professor and chair, Department of Urology, and director, Kimmel Cancer Center Network, Thomas Jefferson University, shared his insight on the recent FDA approvals and other ongoing progress in the treatment of patients with prostate cancer.Gomella: Based on the SPARTAN trial we now have apalutamide, a novel antiandrogen therapy that is available for a group of patients that previously had not much available regarding treatment, except waiting for their disease to manifest and become metastatic. This new drug allows us to treat someone in the “so-called” M0 space with a rising prostate-specific antigen, no evidence of metastatic disease, and castrate levels of testosterone, and now potentially extend life by over 2 years in some cases. This has been a tremendous breakthrough, and this is an area in urologic oncology which we needed something other than just watching these patients go on to progress. We now can offer them hope and extend their overall survival by delaying metastases. We have some agents that are not yet FDA approved, and we have some interesting data with the antiandrogen therapy enzalutamide from the PROSPER trial that may offer a similar benefit [as apalutamide]. This trial included similar groups of men with rising PSAs and castrate level of testosterone, but no evidence of metastatic disease. I would imagine that, at some point in the future, enzalutamide might also be able to achieve an approval in this area. Although it is not yet available in this particular setting, it is available for more advanced cases of prostate cancer.Having all of these drugs moved earlier and earlier in the treatment course of prostate cancer is very exciting. Now having abiraterone available to us for patients who have high-risk prostate cancer who are likely to progress can delay that progression and the development of metastases, which is a very exciting development. We have had these drugs available now to us for the last 4 or 5 years, so we are becoming very familiar with them. The opportunity to use them earlier in the course will hopefully extend the survival of these men and delay their development of systematic metastases.The customized immunotherapy that was approved almost 8 years ago, sipuleucel-T (Provenge), continues to be one of the mainstays of treatment for patients with advanced prostate cancer. Some institutional trials and other large national trials are now looking at combining sipuleucel-T with other agents, such as enzalutamide. An immuno-oncology drug with a novel antiandrogen treatment like enzalutamide may prove to be a benefit to patients with prostate cancer. Taking these advanced drugs and using them together in a long-term sequential fashion may prove to be beneficial. Immunotherapy in prostate cancer continues to be something that we are looking to do better with. Bladder and kidney cancer have been the highlights of the immune-oncology activity in urologic oncology over the last couple of years. Furthering our understanding on how to optimize the use of immune-oncology in prostate cancer will continue to warrant a lot of attention. Hopefully we will be able to replicate some of the significant advances that we are seeing in other genitourinary tumors. What we are starting to see is an increasing recognition of precision medicine in urology. This is an area of doing more targeted therapies. We are certainly not talking about just the tumor anymore, but there is a vested interest in germline mutations like BRCA1/2, ATM, and CHEK2 gene germline abnormalities. These are going to give us some directionality for how we treat patients with prostate cancer across the board. Most of the attention in this area is focused on advanced CRPC, maybe giving us some clue as to what are the best agents to use. However, the future is going to be in screening and defining who the best patients to be screened are to give them the best outcome in the long term.We continue to work with some novel agents and hope to have some of the first-in-human studies of new drugs that we have shown in the lab to have tremendous activity in the setting of metastatic CRPC. One of our highlights over the last year was a major symposium and consensus meeting that we had that was just published in the Journal of Clinical Oncology. We brought a very unique group of individuals together—clinicians specializing in all of the subspecialties of prostate cancer, bioethicists, researchers, and patient advocates&mdash;who sat and spoke as a group with over 70 individuals on the best approaches to using genetic testing for inherited prostate cancer risk.

This is an area that we continue to be actively involved with, and we are working with several large studies such as the Genetic Evaluation of Men (GEM) study, which is trying to further refine how to optimize genetic testing. It is well known how to approach it in women with breast and ovarian cancer, and we are kind of finding our way with prostate cancer. We are realizing there are a lot of similarities between breast and ovarian cancer, as well as other malignancies.


  1. Small EJ, Saad F, Chowdhury S et al. SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol. 2018;36 (suppl 6s; abstr161).
  2. Hussain M, Fizazi K, Saad F, et al. PROSPER: a phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC). J Clin Oncol. 2018;36 (suppl 6S; abstr 3).
  3. Fizazi K, Tran N, Fein LE, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate Cancer. N Engl J Med. 2017;377:352-360. doi: 10.1056/NEJMoa1704174.
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