Mehmood Hashmi, MD, discusses the newly defined landscape of nonmetastatic castration-resistant prostate cancer, the potential with immunotherapy, and emerging imaging modalities.
Mehmood Hashmi, MD
Recent approvals in the setting of nonmetastatic castration-resistant prostate cancer (CRPC) continue to advance the field, explained Mehmood Hashmi, MD.
In July 2018, the FDA approved enzalutamide (Xtandi) for the treatment of patients with nonmetastatic CRPC. The decision was based on data from the double-blind phase III PROSPER trial, in which the combination of enzalutamide and androgen deprivation therapy (ADT) reduced the risk of metastases or death by 71% compared with ADT alone.1 Median metastasis-free survival (MFS) was 36.6 months with enzalutamide plus ADT versus 14.7 months with ADT alone (HR, 0.29; 95% CI, 0.24-0.35; P <.0001).
In February 2018, the FDA approved apalutamide (Erleada) as the first drug to be authorized for use in nonmetastatic CRPC. The approval followed results of the phase III SPARTAN trial, which showed a 72% decrease in the risk of metastases or death with apalutamide versus placebo. Median MFS was 40.5 months versus 16.2 months in the apalutamide and placebo arms, respectively (HR, 0.28; 95% CI, 0.23-0.35; P <.0001).2
These approvals have in many ways fulfilled an unmet need for patients with nonmetastatic CRPC, said Hashmi. Moreover, improvements in imaging modalities will help close the gap by identifying those who can receive aggressive treatment upfront and those who can avoid unnecessary therapy, he added.
In an interview during the 2018 OncLive® State of the Science Summit™, A Summer of Progress: Updates from ASCO 2018, Hashmi, an assistant professor of Medicine at University of Kansas Medical Center, discussed the newly defined landscape of nometastatic CRPC, the potential with immunotherapy, and emerging imaging modalities.Hashmi: Prostate cancer is the most common cancer in men and the second-leading cause of cancer death. In the last 10 years, we saw major improvements in cancer survival, specifically due to [improvements in the treatment of patients with] prostate cancer. 2018 has been a very fruitful year, as well. Several studies were presented, specifically the SPARTAN and PROSPER trials. These trials were [conducted] in patients with nonmetastatic CRPC, which is a group of patients whose needs had never been met before.
Apalutamide, which is one of the newer androgen receptor¬—signaling inhibitors, showed improvement in MFS. Similarly, enzalutamide showed benefit in multiple outcomes in the PROSPER trial. Apalutamide has changed the standard of care. There are several other ongoing studies that were presented at the 2018 ASCO Annual Meeting that addressed treatment intensification, early-stage prostate cancer, combinations, the role of immunotherapy, and some of the new PARP inhibitors that might have a role in prostate cancer.The SPARTAN study was a very exciting 2-arm trial. The trial [tested] standard ADT plus apalutamide versus placebo with ADT, and investigators looked at MFS. There was a difference of about 24 months between arms. Metastasis can lead to significant morbidity and [impair] quality of life. This trial was very promising and has changed our practices.
Although several trials were presented at the 2018 ASCO Annual Meeting, some newer technologies or imaging modalities [were discussed, as well]. The data with prostate-specific membrane antigen (PSMA) scans are very promising. PSMA scans will further help identify a patient’s disease earlier in time.
We also looked at the role of immunotherapy. Although some trials were negative, they paved the way for combination treatments with PD-1 inhibitors, which are showing a lot of benefit in many other cancers. There is a lingering question of how we are going to use [immunotherapy] in prostate cancer. There is a specific subset of patients who are going to benefit from [immunotherapy].
Additionally, a phase II study combined abiraterone acetate (Zytiga) with olaparib (Lynparza) in heavily pretreated patients. Composite results have led to phase III trials.Prostate cancer is a very immunogenic cancer. It produces neoantigens that can be targeted. As in many other cancers, immunotherapy is another available pillar of treatment. As a monotherapy, response rates are not that high. [They hover] around 10%. We have to enhance this response rate. It appears that the combination therapies will have more of a synergistic effect—either dual immunotherapies or immune therapies along with androgen suppression.
We also have to identify some of the particular genes through genomic-based testing to identify and specifically personalize those treatments. However, even with these advances, immunotherapy will be restricted to a certain subset of patients.We always compare which data addressed the most specific needs of the patient. [These were] not head-to-head trials, so we can't scientifically compare them. The safety of the drugs [is also a] major thing we look at. Thirdly, although it doesn't [immediately] affect our clinical decision making, financial toxicity is a major issue these days. We also have to compare prices and look at copay availability for patients. Traditionally, the drug that comes in that particular setting first gets a head start, but we have to compare it scientifically.Traditionally, we’ve done CT scans or bone scans in patients with prostate cancer. Although [these modalities help] us identify a patient’s disease, their sensitivity is not that high. It hovers around 60% to 65%. There was always an unmet need in improving imaging modalities to [identify] patients who can receive more aggressive treatment upfront and those who can avoid unnecessary treatment.
Although carbon-11 PET scan is a modality that is included in the NCCN guidelines and has approximately 80% sensitivity, it is not readily available at all centers. There are specific institutes that can provide it. Although it is scientifically very helpful, there are certain logistical issues.
PSMA-PET scan is another approach that is becoming more common over time. PSMA scans show higher sensitivity and higher positive predictive values at around 80% or so. When all of these modalities become readily available, they will help us identify patients who can be treated aggressively in the beginning, as well as those who can avoid unnecessary aggressive surgeries and radiotherapy toxicities.