Blog

More than one year in to the COVID-19 pandemic, cancer researchers and clinicians are now accustomed to presenting and discussing their findings virtually. From across the globe, thousands of experts logged in to the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting to share cutting-edge research, with the ultimate goal of moving the needle towards cures for patients.

PCF-funded investigators were well-represented among the prostate cancer studies. There were more than 60 abstracts authored by PCF Young Investigators and/or PCF Challenge Award winners. Over 10 total studies were funded by PCF.

Here are some highlights from the prostate cancer presentations. Key themes included PSMA-targeted therapies, combination treatments for metastatic disease, and disparities in treatment for Black men with prostate cancer.

The Big News: PSMA-Targeted Therapy

PSMA stands for prostate specific membrane antigen. It’s been in the news a lot recently, as decades of research are coming to fruition. This protein is found in large amounts on the surface of prostate cancer cells, and can be used as a target to deliver a radioactive, cancer-killing payload to even the smallest bits of cancer anywhere in the body.

A Promising Phase 3 Clinical Trial: PCF-funded researcher Dr. Michael Morris presented results of the large, international VISION trial. This trial randomized patients with metastatic castration-resistant prostate cancer (mCRPC) to treatment with a PSMA-targeting radionuclide therapy called ¹⁷⁷Lu-PSMA-617 + best standard of care or best standard of care alone. Patients treated with ¹⁷⁷Lu-PSMA-617 were approximately 40% less likely to die and 60% less likely to have disease progression on scans. This data will be used as part of an application for FDA approval of this new therapy. Read more on the VISION trial here.

Early Evidence For Another PSMA-Targeted Treatment: Other approaches—using different types of PSMA-seeking “arrows” and radioactive payloads—can be used to target PSMA on prostate cancer cells. A PCF-funded phase 1 trial presented by Dr. Scott Tagawa showed that the investigational drug ²²⁵Ac-J591 was well-tolerated, and nearly 70% of patients showed a decreased PSA. A follow-up study is underway.

Combining Immunotherapy with PSMA-Targeted Treatment: To date, immunotherapy (with pembrolizumab) has had limited use in prostate cancer. A PCF-funded phase 1 trial demonstrated that a single dose of ¹⁷⁷Lu-PSMA-617 combined with pembrolizumab is well-tolerated and can lead to durable responses in some patients with mCRPC.

Long-Term Side Effects of PSMA-Targeted Treatments: It’s crucial to understand potential long-term effects of these investigational therapies. PCF Young Investigator Dr. Scott Tagawa and colleagues combined data from several trials with at least 6 months of follow-up that were conducted at Weill Cornell Medicine, and found that long-term side effects related to PSMA radionuclide treatments were infrequent. It’s important to note that there are other agents under investigation for use as PSMA-targeted treatments that may have more (or less) side effects, that were not included in this study.

What this means for patients: A growing body of evidence suggests that PSMA-targeted therapy may become the “fifth pillar” of treatment for prostate cancer (joining surgery, radiation, chemotherapy, and immunotherapy). ¹⁷⁷Lu-PSMA-617 is furthest along, with other agents being studied. Such an option is urgently needed, especially for patients who have exhausted other approaches. Read more on the history of PSMA science here.

Other Promising Results

PCF-funded researcher Dr. Julie Graff showed that adding pembrolizumab to enzalutamide has a manageable safety profile and anti-tumor activity in some patients with mCRPC that has become resistant to enzalutamide. The treatment combination is being further studied an ongoing phase 3 trial. What this could mean for patients: A potential new approach to overcoming resistance to androgen receptor-directed therapy.

For metastatic hormone-sensitive prostate cancer (mHSPC), combination therapy is standard of care: ADT with either docetaxel, radiation to the primary tumor, or a novel hormonal agent. Now, results from the PEACE-1 phase 3 trial showed that adding abiraterone to ADT + docetaxel significantly improves time to progression on scans in men with mHSPC by 2.5 years, with little additional short-term toxicity. What this could mean for patients: 3 medications may be better than 2 in mHSPC.

Bipolar androgen therapy (BAT) is an experimental treatment which rapidly cycles testosterone levels from extremely high to extremely low. In a PCF-funded phase 2 trial of patients with mCRPC, Dr. Mark Markowski and team found that treatment with BAT plus the checkpoint immunotherapy nivolumab is a promising combination, with some patients having durable responses. Most side effects were low-grade. What this could mean for patients: A new treatment option for men with mCRPC.

Fractures can be a side effect of treatments for mCRPC. The phase 3 PEACE-3 trial found that bone-protecting agents such as denosumab or zoledronic acid strongly protect against fractures in patients receiving enzalutamide alone or enzalutamide + radium-223. What this means for patients: If you’re being treated with enzalutamide or another androgen receptor-directed therapy, or radium-223, talk to your doctor about whether a bone health agent is right for you.

Black men are more than 2x more likely to die of prostate cancer vs Caucasian men. Two things that can help save lives in prostate cancer are 1) knowing about gene mutations in the tumor, and 2) clinical trials. PCF Young Investigator Dr. Brandon Mahal compared use of these approaches in men with prostate cancer of African descent vs men of European descent. Men of African descent had a similar frequency of gene mutations that can affect choice of treatment. However, men of African descent were more likely have tumor gene testing performed later in their treatment course, and were less likely to be treated on clinical trials. What this means for patients: There is disparity in use of biomarker testing and in treatment for Black men with prostate cancer, which may explain some of the disparities in outcomes.

Adding docetaxel or androgen receptor-directed therapy to ADT improves survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC). These “intensified” treatments options have been recognized as standard of care starting in 2015. PCF-funded investigator Dr. Stephen Freedland explored real-world use of such combination therapy and found that in 2018, less than 1/3 of men with mHSPC received intensified treatment. Black patients were less likely to receive intensified treatment vs white patients. What this means for patients: Despite several new life-extending treatments since 2015, most men diagnosed with mHSPC continue to receive ADT alone as first-line treatment. Moreover, there are disparities in treatment along racial lines.

Newer androgen receptor-directed therapies have improved outcomes in mCRPC. However, the cancer eventually becomes resistant, commonly driven by changes in the androgen receptor.  PCF-funded investigator Dr. Johann de Bono presented results from a first-in-human study of a novel oral treatment called TAS3681 that can inhibit the androgen receptor and altered receptors called AR-SVs. What this could mean for patients: A new treatment for mCRPC that overcomes cancer’s resistance to hormone therapy. 

Certain proteins on the surface of cancer cells may serve as new drug targets and/or “biomarkers” that provide information about disease burden or response to treatment. A PCF-funded study found that a protein called TROP-2 in men with mCRPC shows promise as a therapeutic target and biomarker. What this could mean for patients: A new approach to treating mCRPC.