First-Ever Clinical Trial Testing PSMA-Targeted Antibody and Radioactive Alpha Particles for Treatment of Advanced Prostate Cancer

Radiation is one of the most common treatments for prostate cancer. Using radiation, physicians are able to cure some men with cancer confined to the prostate, as well as improve symptoms for men with metastatic disease. There are many different types of radiation treatments.

One type of treatment includes injecting radioactive isotopes into the blood in order to directly reach the prostate cancer cells regardless of where they are located in the body, including the cells that have spread to the bone and other organs. For example, Radium-223 (Xofigo) is FDA-approved to treat prostate cancer that has metastasized to the bone and has been shown to improve both the quality and duration of the lives of men with advanced prostate cancer.

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Red marker = PSMA, Green = radiation, demonstrating that the drug targets the cancer cell directly.

Radioimmunotherapy or radioligand therapy involves the practice of attaching a radioactive isotope to a cancer-targeting antibody or small molecule that binds only to a specific cancer-related molecule on a tumor cell. This is similar to a “lock and key” scenario, where the antibody or molecule resembles the key that will only recognize a very specific lock (the cancer-related molecule).

Essentially all prostate cancers have a specific “lock” called prostate-specific membrane antigen (PSMA). This “lock” is a protein that sits on the surface of most prostate cancer cells but is absent from most other normal places in the body.

Physicians and scientists have engineered very specific “keys” in the form of monoclonal antibodies and molecules that will bind only to PSMA. When we attach radioactive particles to these keys, we are able to deliver what we call “molecularly targeted” radiotherapy.

For example, J591 is a monoclonal antibody (an engineered protein) that recognizes PSMA. Actinium-225 (225Ac) is a small radioactive particle that emits alpha-particles, a powerful form of radiation requiring fewer particles to cause damage to the cancer cells. When these are attached to one another, we call the compound 225Ac-J591 (a radioactive particle linked with a monoclonal antibody). It is designed so that J591 will recognize the PSMA on the prostate cancer cells and bring the radioactive particle 225Ac with it into prostate cancer cells wherever it goes in the body.

Our physicians and scientists are building on prior laboratory-based research presented at the 2017 Meeting for the Annual Association for Cancer Research (AACR) and are now studying the role this experimental therapy may have for men with advanced prostate cancer that has spread throughout the body. Thanks to generous support from the Prostate Cancer Foundation and the NIH SPORE award, Dr. Scott Tagawa, medical oncologist and Director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, and his team are conducting the first-ever clinical trial testing the PSMA-targeted antibody and radioactive alpha particles (225Ac-J591) for treatment of advanced prostate cancer. This promising new and unique approach has the potential to lead to another treatment option for those patients who are not experiencing the best clinical outcomes possible from standard of care therapies. Some men in Germany have received 225Ac linked to PSMA-617 with a handful of cases published with impressive responses. However, no formal studies have been performed and there are reports of bothersome dry mouth (xerostomia) and the potential for delayed kidney damage (seen in mice).

“We look forward to advancing science and also making this treatment available to men with advanced prostate cancer in the near future, says Dr. Scott Tagawa. “Our goal is to translate the existing knowledge base into true clinical gains for prostate cancer patients and it’s great that in October, 2017, we are able to treat our first patient.”

 

 

 

Prostate Cancer Education Seminar Presented as Part of WCM/NYP Health and Wellness Fall Series

Each fall, Weill Cornell Medicine (WCM) and NewYork-Presbyterian (NYP) host a health and wellness seminar series – one seminar every week for a month – where physicians educate the local community about different types of health issues.

Tagawa and Nanus Prostate TalkLast week, Dr. David Nanus, professor of medicine and urology at Weill Cornell Medicine and Dr. Scott Tagawa, medical oncologist and Director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, presented to and educated people in the local community about prostate cancer. Their presentation was titled, “Your Guide to Prostate Health and What to Know About the Leading Cancer in Men.” Following the presentation, all attendees were invited to ask the physicians questions.

Nanus Prostate Talk
Some of the key topics from Dr. Nanus and Dr. Tagawa’s presentations included the common risk factors for prostate cancer, the importance of screening, the latest treatments and research, as well as utilizing the precision medicine approach.

 

Key highlights from their presentations are outlined below.

 Prostate Cancer Risk Factors

Prostate cancer risk factors include age, ethnicity and inherited genetic conditions. For example, those diagnosed with prostate cancer are predominantly older men. Additionally, new data points towards a surprisingly high percentage with inherited cancer genes. Those with genetic conditions such as BRCA 1 or BRCA 2 or those with prostate cancer in their family history are also more likely to be diagnosed with the disease.

Early Detection and Screening

Dr. Nanus and Dr. Tagawa highlighted the importance of screening and early detection by referencing the recently-updated National Comprehensive Cancer Network (NCCN) prostate cancer screening guidelines. Despite ongoing debate over the value of prostate cancer screening, this past September, NCCN’s guidelines suggest that screening canTagawa Prostate Talk indeed reduce a man’s risk of dying from the disease and that prostate-specific antigen (PSA) testing and digital rectal examination (DRE) should be done. Newer tests are also available to assist in counseling about biopsies and targeted biopsies are now offered at selected centers. Dr. Scott Tagawa addressed the importance of the “shared decision-making” model when it comes to prostate cancer screening. For example, men considering screening are encouraged to discuss with their healthcare team and family members the pros and cons of getting screened and what the best course of action would be if the results lead to a diagnosis.

Treatments

The presentation also addressed the different treatment approaches. As a first step, the most important factor in choosing the best way to treat prostate cancer is knowing what stage the cancer is in. Prostate cancer has been traditionally staged and “risk-stratified” based on the extent of the cancer (using T, N, and M categories) and the PSA level and Gleason score at the time of diagnosis.

We now have additional molecular tests to add prognostic value. In certain circumstances, these tests assist in the decision for “radical treatment” which has been traditionally performed with surgery and/or radiation versus active surveillance (which entails regular monitoring visits in addition to repeat imaging/biopsy). It is important to note that most men diagnosed with prostate cancer, including some that have recurrence after surgery or radiation, will never die of the disease.

Novel molecular imaging techniques have assisted in telling physicians and researchers about the location of previously unseen cancer and also providing information about the biology of certain tumors. A number of therapeutic advances have occurred over the last several years resulting in men with incurable cancer living longer with a better quality of life.

Precision Medicine

Dr. Tagawa emphasized the great strides and therapeutic advances over the years in prostate cancer treatments, but that more work still needs to be done. There are now many options for therapies that make men live longer while also making them feel better. One of the reasons for this advancement is the use of precision medicine, which means that physicians are treating each individual based on their own genetic makeup without using a “one size fits all” type of approach. A key factor in making this method successful is through clinical trials. We often interrogate a patient’s tumor from surgery or an image-guided needle biopsy. In addition, liquid biopsies are now increasingly valuable.

View this FOX 5 clip featuring Dr. David Nanus and Dr. Scott Tagawa with their patient, Alex Sarmiento, who was diagnosed with prostate cancer and tested with a liquid biopsy.

Research

Data shows that most adults with cancer do not participate in clinical trials. It is through clinical trials that new treatments and combinations of treatments can be identified. Clinical trials pave the way toward further scientific advances that could potentially help to find a cure for prostate cancer, and other cancers as well. These trials also have the ability to offer therapies to patients that they otherwise would not have access to. The most common reason that patients do not enroll in clinical trials is because they were not told that this was an option. We suggest asking your physician about access to clinical trials at each stage of the disease and/or seeking out centers that have trials available.

Weill Cornell Medicine and NewYork-Presbyterian offers many prostate cancer-specific trials that you can search for here.

Success of Abiraterone Trials Prompts ‘Mind Shift’ in Prostate Cancer Treatment

The below has been adapted and excerpted from an article in Healio in which Dr. David Nanus HeadshotNanus comments on The LATITUDE and STAMPEDE trials — results of which were presented at this year’s ASCO Annual Meeting and subsequently published in The New England Journal of Medicine. Read the full story here.

Abiraterone acetate is poised to challenge docetaxel as the standard addition to androgen deprivation therapy for treatment of newly diagnosed, metastatic castration-resistant prostate cancer. The LATITUDE and STAMPEDE trials showed the addition of abiraterone acetate and prednisone to androgen deprivation therapy (ADT) reduced risk for death by nearly 40%.

Docetaxel — an IV chemotherapy — can cause nausea, constipation, diarrhea, neutropenia or fatigue during its 18-week dosing schedule. Abiraterone, an oral adrenal inhibitor traditionally used in later-line therapy, is administered until disease progression and has relatively few side effects.

Docetaxel became the standard of care in patients with metastatic hormone-resistant prostate cancer following results from the CHAARTED study, published in 2015 in The New England Journal of Medicine. The results, based on median follow-up of 28.9 months, showed docetaxel improved median overall survival (OS) from 44 months to 57.6 months.

Abiraterone typically has been reserved as second-line therapy for men resistant to ADT. The LATITUDE and STAMPEDE trials — both supported by Janssen, the manufacturer of abiraterone — evaluated whether abiraterone would be more beneficial if used earlier.

Although abiraterone conferred unprecedented survival benefits and is better tolerated, not all oncologists agree it should replace docetaxel in the absence of a head-to-head comparative trial.

HemOnc Today asked urologic oncologists and researchers about the promise of abiraterone; the potential impact of its long-term use; if its cost in comparison with docetaxel is prohibitive; and whether abiraterone soon will be challenged by other therapies for the treatment of metastatic hormone-resistant prostate cancer.

“Abiraterone is a whole new paradigm because your patient is not coming in for an infusion every few weeks for six cycles,” David M. Nanus, MD, professor of medicine and urology at Weill Cornell Medicine, told HemOnc Today. “With six cycles of docetaxel, patients are often wiped out by the time they’re done, and it might take a few months to recover afterward.”

Based on the findings of the LATITUDE and STAMPEDE trials and the potential of targeted therapy, oncologists with whom HemOnc Today spoke agreed researchers are on the precipice of significantly extending the lives of men with prostate cancer.

In addition to the enthusiasm surrounding abiraterone and its potential to be the new standard of care in the treatment of metastatic, castration-resistant prostate cancer, several ongoing clinical trials are investigating other strategies to reduce androgen exposure. Results of those trials also could be practice changing, and again raise questions about the standard of care.