Ahmad S. Halwani, MD — George E. Wahlen VA Medical Center — Salt Lake City, UT

SALT LAKE CITY — Accounting for nearly a third of all cancer diagnoses, prostate cancer is the most frequently diagnosed cancer in the VHA, where past research has suggested that the malignancy is caught earlier than in other healthcare systems.

Those patients generally can anticipate a long life—the 15-year survival rate in that situation is 96%.
For veterans whose disease is caught at a later point, however, the prognosis is not as good: Just 29% live five years or more after diagnosis of metastatic disease.

Standard treatment for metastatic disease involves androgen deprivation therapy (ADT), which leads to a sharp drop in prostate-specific antigen response and clinical improvements in virtually all patients. The majority eventually develop castration-resistant prostate cancer, and many will subsequently experience further metastasis.

Until recently, the primary treatment for metastatic castration-resistant prostate cancer (mCRPC) was immediate use of systemic chemotherapy, but the field has changed radically since 2010. “Over the past decade, no less than six non-chemotherapy treatments have been approved for prostate cancer by the FDA. These include abiraterone, enzalutamide, cabazitaxel, sipuleucel-T, denosumab, and radium-223,” said Ahmad S. Halwani, MD, of the George E. Wahlen VA Medical Center in Salt Lake City.

Those therapies have delayed chemotherapy and added survival time. For example, enzalutamide combined with gonadotropin-releasing hormone analogue (GnRH-a) therapy has been shown to significantly delay time to cytotoxic chemotherapy initiation by a median of 28.0 months vs. 10.8 months with placebo.1

In a study presented at the European Society for Medical Oncology annual meeting and published in the Annals of Oncology, Halwani and his colleagues linked information in the VA Clinical Cancer Registry to the VA Corporate Data Warehouse to evaluate the impact of the new agents on treatment for mCRPC at the VA.2

The study team identified 120,374 veterans with prostate cancer who received treatment at the VA between 2006 and 2015, of whom 3,637 had mCRPC. They found that the approval of newer agents not only changed how patients were treated, they changed who received treatment.

Patients diagnosed with mCRPC between 2011 and 2016 received cytotoxic therapy at much lower rates than patients diagnosed between 2006 and 2010, 22% vs. 37%. Prior to 2011, the majority of veterans with mCRPC did not receive any treatment (56%). After the approval of the new drugs, 62% received treatment and more than a third of patients (37%) had more than one line of therapy, up from 20% in the earlier period.

“We hypothesize that newer agents have a more favorable utility profile that facilitates their use in real-world settings in the first line and subsequent lines,” Halwani told U.S. Medicine. “This allows treatment of patients who would not have been candidates for chemotherapy in the past, and the utilization of more lines of therapy over the disease course.”

The researchers also looked at which of the antineoplastic agents physicians used and in what order. From 2011-2016, the most common first-line agent was abiraterone, which 29% of patients received. In the second-line setting abiraterone (15%) and enzalutamide (14%) were used about equally. As a third-line therapy, enzalutamide was the most common.

“Oncology as a field is moving away from chemotherapy and increasingly adopting more targeted therapy due to their overall favorable efficacy and safety compared to chemotherapy. In our study of treatment practices in mCRPC, we found evidence for both of these trends,” Halwani said.

With the growing number of therapies available, more research and guidance on their use is needed, he added. “Going forward, there remains a need to understand the optimal timing and sequence for the use of these agents to both improve mortality and morbidity (such as primary or secondary prevention of skeletal-related events),” he said.

Racial differences in mCRPC

The study also sought to understand more about differences in the incidence and course of prostate cancer between non-Hispanic white men and black men. “Black men have an increased incidence of prostate cancer, are diagnosed at an earlier age than white men with similar demographic and disease characteristics and experience worse clinical outcomes,” Halwani explained.

While other researchers have suggested that prostate cancer has a more aggressive course in black men, other factors could contribute to differences in incidence and outcomes. “It is typically challenging to isolate biological factors from non-biological factors that can lead to disparities in access and treatment practices,” Halwani noted. A significant underrepresentation of black men in clinical trials for mCRPC drugs further complicates the picture, he said.

“We hypothesized that the VA provides an important setting for the study of practices and outcomes of black men with prostate cancer, especially that our prior work suggested good representation of black men in the veteran population, at about 11%, comparable to the national average, and the VA has social support mechanisms that can compensate for decreased access,” Halwani said.

The researchers found that black veterans were younger on average when diagnosed with metastatic CRPC and had higher prostate-specific antigen values at diagnosis. Within the VA, “their treatment patterns were similar to other groups,” and they had similar rates of use of the newer antineoplastic agents, Halwani said.

Understanding the differences in how prostate cancer progresses is just one factor in gaining the upper hand against the disease. “Prostate cancer is an extremely heterogeneous disease with some patients having an indolent course where the toxicity of treatments outweighs their benefit,” Halwani noted.

“Differentiating patients with aggressive disease who will therefore benefit from treatment vs those with indolent disease that are better off with watch-and-wait strategies remains one of the most important challenges in this space.”

1Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, et. Al. PREVAIL
Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33. doi: 10.1056/NEJMoa1405095. Epub 2014 Jun 1. PubMed PMID: 24881730; PubMed Central PMCID: PMC4418931.

2Halwani A, Burningham Z, Rasmussen KM, Patil V, Narayanan S, Lin S-W, Carroll S, Hsu L-I, Graff J, Dreicer R, Gupta S, Low C, Sauer BC. 804P: Practice patterns in metastatic castration-resistant prostate cancer (mCRPC): Evidence from the veterans health administration. Annals of Onc. 1 Sept 2017; 28(S5).