What Patients with Prostate Cancer Should Know About PSMA Imaging and Therapy

Prostate cancer begins when cells in the prostate gland start to grow out of control. These cancerous cells may remain in the prostate or metastasize and spread to other parts of the body such as the bones, lymph nodes, liver, or lungs. 

Prostate-specific membrane antigen (PSMA) is a protein found on the surface of prostate cancer cells. PSMA-targeting can be used to locate, identify, or treat cancerous cells in both the prostate as well as cancerous cells that have metastasized in other organs. This targeting can involve attaching a radionuclide, a particle that gives off radiation, to different molecular agents, most often monoclonal antibodies or small molecule targeting agents (also known as peptides, ligands, or inhibitors). This combination attaches to the PSMA receptors located in the cancer cells. 

PSMA positron emission tomography (PET) scans are an imaging technique approved by the U.S. Food and Drug Administration (FDA). PSMA PET is able to precisely locate prostate cancer cells using a radioactive imaging agent that binds to prostate cancer cells to help localize them. This drug is injected into the body and attaches itself to PSMA proteins expressed by prostate cancer patients. The PET scan is then able to detect and pinpoint the prostate cancer tumors.

Weill Cornell Medicine was one of the first centers in the United States offering this technology for patients. PSMA PET is able to identify whether the cancer has spread beyond the prostate gland with higher accuracy than other imaging methods. 

The team at the Weill Cornell Medicine Genitourinary (GU) Oncology Program has been a pioneer for PSMA-targeted therapies for many years. PSMA-targeted radionuclide therapies lead the combination of radionuclide and molecular agents directly to the PSMA cell receptors. The ability for the targeting agents and the PSMA receptors to join together provides this therapy the ability to precisely target prostate cancer cells.  

In March 2022, the FDA approved 177Lu-PSMA-617 (also known as Lu 177 vipivotide tetraxetan or Pluvicto) for the treatment of patients with metastatic castration-resistant prostate cancer. Dr. Scott Tagawa, director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program, was a member of the steering committee for the trial evaluating this treatment that led to the approval. 

“The first availability of tumor-targeted radionuclide therapy on a commercial basis will allow patients with more limited resources that might not have been able to travel for a clinical trial or overseas to receive the benefit of this treatment. The first successful phase 3 trial allows us in research to optimize the treatment, study it in earlier disease states, and explore combinations with other therapies with scientific merit. Even after this approval, I encourage clinical trial participation and/or referrals.”

Scott Tagawa, MD, MS

Weill Cornell Medicine will be one of the first centers able to offer this therapy to patients immediately for both our existing patients and those who may be referred to us if their local provider doesn’t immediately have access to this therapy.  

Our team continues to lead and participate in a number of clinical trials aimed at ongoing testing and research for additional PSMA-targeted imaging and treatment. We are one of few centers in the world currently able to provide treatment plans that involve both PSMA-PET imaging and multiple PSMA-targeted therapies for our patients, as well as the opportunity to participate in these types of clinical trials in order to further develop PSMA technology.  

The Weill Cornell Medicine Genitourinary (GU) Oncology Program provides top-notch care, knowledge, and expertise for our patients. We offer new patient appointments, second opinions, and ongoing care for people with genitourinary cancers, including prostate cancer. To learn more or to make an appointment with one of our physicians, please call us at 646-962-2072. If interested in a clinical trial, please email us at guonc@med.cornell.edu.

New Team Member: Dr. Cora Sternberg

We are very excited to welcome Cora Sternberg, MD, to the Genitourinary (GU) Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian Hospital.Sternberg Welcome_Facebook

Dr. Sternberg is a leading international researcher and world expert in the field of medical oncology, genitourinary (GU) cancers, and drug development. She is known for her influential work in developing novel therapies and targeted agents for the treatment of prostate, renal and bladder cancers.

In her new role, Dr. Sternberg will facilitate the continued growth and development of clinical and translational research programs in genitourinary (GU) malignancies. She will also serve as Clinical Director of the Englander Institute for Precision Medicine (EIPM), developing strategies to incorporate genomic sequencing and precision medicine throughout the Weill Cornell Medicine and NewYork-Presbyterian healthcare network, including Lower Manhattan, Brooklyn and Queens.

Visit Dr. Sternberg’s profile to learn more about her medical experience and accomplishments.

 

ESMO: Day 3 Recap

At ESMO 2017, Sunday, September 10th was the day with the largest number of genitourinary (GU) cancer presentations, including two kidney cancer and urothelial cancer highlights in the Presidential Symposium, many poster presentations, and two poster discussion sessions. We’ve broken down the full day of research updates by cancer type.

Kidney Cancer

ESMO_CheckMate 214In the Presidential Presentation on kidney cancer, results were presented from the CheckMate-214 trial. Nivolumab is an anti-PD1 antibody approved for patients with advanced renal cell carcinoma (RCC) previously treated with a VEGF-targeted therapy based upon a randomized trial demonstrating an overall survival benefit. The combination of using immune checkpoint inhibitors transitioned from laboratory science to safety studies to full approval in melanoma based upon randomized trials. The CheckMate 214 study tested the efficacy of the combination of nivolumab plus ipilimumab versus one of the most standard VEGF multikinase inhibitors, sunitinib, in previously untreated patients with advanced RCC. The study focused on the intermediate/poor risk population, but also enrolled patients with good risk disease. The study met its endpoints in an impressive fashion. In the target intermediate/poor risk population, the immune checkpoint inhibitor combination led to an improved response rate and overall survival benefit versus the active drug sunitinib. Nine percent of patients had a “complete response” with the combination immunotherapy (meaning complete disappearance of all evidence of cancer on scans). In addition, the entire patient population (with patients in all prognostic groups combined) experienced an improvement in both response and overall survival with immunotherapy.  There were some interesting exploratory analyses of subgroups and the PD-L1 expression status that will lead to additional investigation, but the study will lead to a paradigm shift and create a new standard of care for patients with advanced RCC.

In the Alliance-led A031203 “CaboSun” study, patients with intermediate and poor-risk advanced renal cell carcinoma (RCC) were randomized to receive either cabozantinib or sunitinib. The initial results of the study as assessed by the investigative team showed a benefit of cabozantinib over sunitinib in terms of the trial’s primary endpoint of overall survival. One previous caveat of the study was that interpretation of scans by investigators who are also the treating physicians can be biased. An updated analysis added independent review of scans as well as longer follow up. The progression-free survival benefit of cabozantinib was confirmed by independent review and the magnitude of benefit was increased with longer follow up.

Approximately a third of patients with advanced RCC have bone metastases and this may be a negative indicator of prognosis (also known as a “negative prognostic factor”). Radium-223 is an FDA approved agent for men with metastatic castration-resistant prostate cancer and predominant bone metastases that has been shown to benefit overall survival. A team of investigators from Boston assessed whether adding radium-223 to standard sunitinib or pazopanib would also benefit patients with kidney cancer. The combined treatment was determined to be safe and and markers in the blood and urine indicating that the bone is breaking down – a measure of bone metastases – improved with treatment. Additional randomized trials are needed to assess the true effect of this combination on overall survival.

Bladder and Urothelial Cancer

ESMO_RANGEDuring the ESMO Presidential Presentation on urothelial cancer, results from the RANGE clinical trial were presented. The utility of chemotherapy is limited in patients with advanced urothelial carcinoma whose cancer has progressed after initial platinum-based chemotherapy. Ramicurimab is a monoclonal antibody against the angiogenic factor receptor VEGF-R2. We performed a randomized phase II trial pointing towards a response and progression-free survival benefit with the addition of ramicurimab to docetaxel chemotherapy in this patient population. The RANGE study is a phase III study in which patients with advanced platinum-resistant urothelial carcinoma, with or without treatment with an immune checkpoint inhibitor, were randomized to docetaxel with ramicurimab or placebo. This phase III trial confirmed the benefit of ramicurimab when added to docetaxel in improving progression-free survival and response rate. In addition, there was no significant additional toxicity with the combination, also referred to as a doublet. We await the final overall survival results and additional analyses to assess the place of this combination in our growing treatment armamentarium for urothelial carcinoma.

Several studies examined the genetic material (genome) of tumors in patients with urothelial carcinoma. In a large clinical trial including more than 2000 patients with advanced urothelial carcinoma, investigators utilized the FoundationOne platform to assess the tumor genome of a mix of primary and metastatic tumors arising from the bladder, renal pelvis, and ureters. The study described the landscape of this disease using the targeted sequencing platform, showing a relationship between some common alterations (such as genes for Her2 and PI3K) and a higher rate of overall mutations or “tumor mutational burden” (also referred to as “TMB”).  An analysis of the Checkmate-275 study which led to the approval of nivolumab in patients with progressive urothelial carcinoma after chemotherapy looked at tumor mutational burden and survival outcomes. Higher tumor mutational burden was associated with both better response and survival in patients treated with nivolumab, a form of immunotherapy called an anti-PD1 checkpoint inhibitor. This result was independent of PDL1 status – a specific measure of this a type of mutational burden–  but perhaps stronger in PDL1 low tumors.

Dr. Scott Tagawa, Medical Director of the WCM/NYP Genitourinary Oncology Program, presented a research update regarding patients with advanced urothelial carcinoma who were treated with sacituzumab govitecan (IMMU-132)  after prior chemotherapy. This drug, which links an antibody against Trop2 (which is usually present to a high degree in urothelial carcinoma compared to normal cells) to a potent chemotherapy metabolite, was administered to 41 patients with cancer progression despite an average of three prior treatment regimens. Significant tumor shrinkage (i.e. partial or complete responses) occurred in 34% of patients. In addition, median progression free survival of approximately 7 months and overall survival of approximately 16 months was impressive compared to the expected rates for this patient population.

Prostate Cancer

Prior prostate cancer research has demonstrated strong links within family trees, and as a result, there has been a large push for research to identify where exactly in the genetic profile this risk comes from and whether these genes are passed down through ancestry. In the UK Genetic Prostate Cancer Study (UKGPCS), investigators performed a case-control study of men with and without germline (inherited) DNA damage response and repair genes (those responsible for repairing the DNA of cells in the body) identified in their 167 gene panel. Like in other studies, those with germline alterations had worse cancer-specific outcomes and overall survival rates. Notably across studies, the presence of these inherited genes is not limited to men diagnosed at an early age, so a discussion with physicians about the risks/benefits of genetic testing should be considered.

Our collaborator Dr. Armstrong of Duke University presented research analyzing PSA changes in the PREVAIL trial which led to the FDA-label expansion of enzalutamide for men with mCRPC and no prior chemotherapy. As he and others have previously demonstrated with other drugs such as docetaxel and abiraterone, a lack of PSA decline while on treatment was associated with a poor outcome.

ESMO_ValeTwo presentations focused on men with hormone-sensitive high risk and advanced prostate cancer.

Dr. CL Vale from the UK presented an analysis of data available from randomized trials which pointed towards abiraterone + androgen deprivation therapy (ADT) having a large early relative survival benefit of 37% after 3 years, and docetaxel + ADT having a smaller, but still large and significant 23% survival impact after additional follow up for 4 years.

In prostate cancer, there is a “TNM” staging system that indicates the size range of the primary tumor (T), whether the cancer has spread to the lymph nodes (N), whether there are signs that the cancer is metastatic and has spread elsewhere in the body (M). When there are no signs of distant metastases, the corresponding staging is “M0” which translates to M zero, or no metastases. ESMO_M0_ProstateCancer

Dr. Nicholas James from the UK presented data on the “M0” population of 915 men without distant metastatic disease receiving abiraterone + ADT versus ADT with or without radiation as part of the STAMPEDE study. In the overall group with M0 disease, so far there have not yet been any detectable differences in survival, which is not surprising since this subset of men tend to live for a long time while on therapy. There were though, important improvements in the amount of time to cancer growth or the development of metastatic disease. In those men with clinically evident lymph node metastases at diagnosis (corresponding to the symbol “N”), the combination of all three treatments — abiraterone, ADT, and radiation — demonstrated a significantly better survival benefit than those treated with ADT + radiation, which was in turn better than ADT alone.

Additionally, new information on interesting early phase clinical trials was also presented at ESMO.

At Weill Cornell Medicine and NewYork-Presbyterian, we participated in a clinical trial utilizing INO-5150, a DNA vaccine against PSA and PSMA. This vaccine was administered with electroporation (essentially a small electric shock at the injection site) and with or without INO-9012 (an IL-12 vaccine) designed as an adjuvant treatment to improve immune responses to the INO-5150 treatment. Men who received either one or both vaccines had few side effects other than skin reactions at the injection site and many developed immune responses. Additional study is warranted to test anti-tumor efficacy.

EC1169 is comprised of a small molecule PSMA ligand linked to a tubulysin drug. Updated data were presented in this trial where men with metastatic castration resistant prostate cancer (mCRPC) who had both received and not received prior chemotherapy were treated with EC1169. As more men were treated on trial, researchers were able to document safety and tolerability of the drug, while demonstrating the drug’s ability to control the cancer, particularly in men who had previously received docetaxel chemotherapy.

In prostate cancer, one of the mechanisms of resistance to hormonal therapy is activation of the PI3K/AKT pathway. GSK2636771 is a PI3K inhibitor that was tested in a phase I study by adding the drug to enzalutamide in men with mCRPC who had experienced some cancer progression while taking enzalutamide alone. Importantly, the trial demonstrated that GSK2636771 was safe and a signal of efficacy was present in the small trial. Additional studies are planned which will be adding the drug to enzalutamide to truly test its ability to control cancer growth. Of note, the PI3K pathway is indicated in the formation and growth of numerous cancers and was discovered by our cancer center director, Lewis Cantley, PhD.

Check out our prior ESMO 2017 Day 1 and Day 2 Recaps.

%d bloggers like this: