Highlights of GU-ASCO 2021: Prostate-Targeting Radionuclide Treatment, Oral Docetaxel, and More
The American Society of Clinical Oncology (ASCO) recently held its 2021 Genitourinary Cancers Symposium virtually. These meetings provide opportunities for clinicians and researchers to share and discuss the latest clinical research findings in prostate and other GU cancers, with the ultimate goal of improving diagnostic approaches and therapies for patients.
Dr. Andrea Miyahira, PCF’s Director of Global Research & Scientific Communications, has compiled 5 Key Highlights in Prostate Cancer Research from this year’s meeting. These include:
- Promising trial results of a radionuclide treatment that targets PSMA on prostate cancer cells
- Combining 2 next-generation androgen directed therapies in patients with castration-resistant cancer
- A strategy to find patients who may better respond to treatment with bipolar androgen therapy
- An oral alternative to IV docetaxel
- A possible combination treatment approach for mCRPC, focusing on bone metastases
Read on for more details.
- New prostate-cancer-specific treatment continues to show promise in patients with mCRPC
Prostate-specific membrane antigen (PSMA) is a protein that is present at high levels on prostate cancer cells. It can already be used in PSMA PET scanning, which was FDA-approved in December 2020, and a promising next step is to use PSMA as a target to deliver radioactive therapies (such as Lu-PSMA) straight to prostate cancer cells wherever they are in the body.
TheraP is the first randomized phase 2 clinical trial comparing Lu-PSMA to a standard of care option, cabazitaxel, in patients who have previously been treated with anti-androgen therapies and docetaxel. Initial results from the TheraP trial showed that many more patients treated with Lu-PSMA saw their PSA drop compared to patients treated with cabazitaxel.
Now, researchers report more promising results for Lu-PSMA, including better progression-free survival (19% vs 3% at 1 year) and overall response rate (49% vs 28%). Among men who reported having pain at the beginning of the study, pain outcomes improved in 60% in the Lu-PSMA arm vs 43% for cabazitaxel. Overall, these results continue to suggest Lu-PSMA is a promising alternative to cabazitaxel.
Lu-PSMA is currently being tested in the randomized phase 3 trial called VISION, which may report results later this year. If the results of this trial are favorable, Lu-PSMA may become a new standard of care treatment option for mCRPC.
- Treatment with two androgen directed therapies shows modest benefit in patients with mCRPC
In castration resistant prostate cancer (CRPC), tumors have become resistant to standard androgen deprivation therapy (ADT), and/or stronger, next-generation androgen directed therapies. New treatment approaches are urgently needed for such patients. Researchers aimed to determine whether two androgen directed medications, with different mechanisms, could better overcome this resistance in patients with mCRPC.
In a phase 3 clinical trial, patients were randomized to receive abiraterone + apalutamide or abiraterone + placebo. Patients on the combination treatment had a significantly longer time (6 months) to worsening disease on scans or death, and more patients had at least a 50% drop in PSA. Overall survival (OS) was not significantly different, although a trend to better OS in the combination arm was noted in certain patient subgroups. More information is needed before doctors can recommend this combination of androgen directed medications in patients with mCRPC.
- Identifying patients who may respond to bipolar androgen therapy
One key goal of precision oncology is to identify patients who are more likely to respond to a particular therapy. Bipolar androgen therapy (BAT) is an emerging treatment strategy for men with mCRPC, whereby testosterone levels are cycled between extremely high to low (castrate) levels each month. BAT has been shown to be safe, and some patients (19% in this study) have shown exceptional clinical responses. This team looked at the tumor DNA of 15 mCRPC patients that had achieved deep PSA responses on BAT. 93% of these patients had a mutation in a specific tumor suppressor gene or a gene involved in repairing damaged DNA. Taken together with other recent findings, BAT appears to hold significant promise, particularly in patients with certain tumor alterations.
- An oral alternative to IV chemotherapy in patients with mCRPC
Docetaxel is part of the standard of care for patients with mCRPC and is currently given as an intravenous (IV) infusion. An oral form of this medication may be more convenient, eliminate infusion-related reactions, and avoid the need for prophylactic steroids, as well as offer safety benefits. During the COVID-19 pandemic, an oral alternative would have decreased the need for regular clinic visits as well.
ModraDoc006/r is a novel, oral tablet version of docetaxel. 90 patients were randomized to the oral or IV form. Preliminary results suggest that ModraDoc006/r may have similar efficacy as IV docetaxel, with lower adverse events of reduced blood cell counts and hair loss. The trial is ongoing to evaluate the data over a longer timeframe, but ModraDoc006/r may be a promising oral option for patients with mCRPC undergoing chemotherapy.
- Combining treatments for mCRPC, with a focus on bone metastases
Enzalutamide and radium-223 are both treatments for mCRPC that improve survival when given on their own. A clinical trial tested whether combining these treatments is safe and a more effective option. In 47 patients with progressive mCRPC, treatment with enzalutamide + radium-223 was associated with lower bone metabolism markers (suggesting less bone metastasis) compared to enzalutamide alone. Two other measures of efficacy were significantly better in patients given the combination treatment. In terms of side effects, two patients in the combination arm developed fractures 15-31 months after the last radium-223 dose, which were asymptomatic and required no intervention.
Overall, this small study found that enzalutamide + radium-223 resulted in significant long-term benefit vs enzalutamide alone in patients with mCRPC without compromising safety. The safety and efficacy of this combination is also being evaluated in the ongoing phase 3 PEACE III study.