ESMO 2017: Day 1 Recap

ESMO LOGOThe 2017 European Society for Medical Oncology (ESMO) annual meeting has officially kicked off and our team has joined approximately 25,000 cancer researchers from around the world to present and discuss the latest cancer research.

Welcome to ESMO 2017_SignWe’ve outlined some key highlights from the first day of the conference below.

For men with newly diagnosed “hormone sensitive” high risk / advanced prostate cancer, several recent studies have changed the standard of care. Data from the CHAARTED, STAMPEDE, and LATITUDE studies that investigated the addition of docetaxel or abiraterone and low dose prednisone to standard androgen deprivation therapy (ADT) for men with advanced prostate cancer has led to significantly longer and better lives. Updates to this data were presented at ESMO 2017.

The STAMPEDE study included an overlapping period where some men were randomized to ADT + docetaxel chemotherapy and others were randomized to ADT + abiraterone/prednisone. It was comforting to know that whether men received either chemotherapy with docetaxel for 6 cycles or abiraterone and prednisone continuously for at least 2 years that they lived significantly longer compared to men receiving the old standard of ADT alone.

The interesting comparison presented at ESMO 2017 was that men who took abiraterone had longer time to cancer progression (mostly assessed by rising PSA). There were similar overall survival outcomes with either initial treatment strategy. As expected, the types of side effects were different depending upon the type of treatment, but severe toxicity was equally common with either type of treatment.

For the first time, “patient reported outcomes” assessing symptoms and quality of life on the LATITUDE study (including men with high-risk metastatic disease treated with ADT + abiraterone/prednisone or ADT + placebos) were presented. In addition to living significantly longer and having major delays in cancer growth, men taking ADT + abiraterone/prednisone had better pain control and were less likely to have reductions in quality of life, particularly after the initial 4 months on treatment.

Prostate-specific membrane antigen (PSMA) is a protein that is on the cell surface of most prostate cancers and can be used as a treatment target since it is not present many other places in the body. At Weill Cornell Medicine and NewYork-Presbyterian, we have been targeting this protein with radioactive particles for more than a decade. Other institutions have also more recently begun using this approach. Over the past several years, there have been many patients receiving this type of therapy in Europe who may have benefitted from this treatment, but no real prospective clinical trials have been performed. Australian researchers presented data at ESMO in which they enrolled and treated 30 men whose tumors “lit up” on PSMA-PET scans with 177Lu-PSMA-617 in a clinical trial. Patients received up to 4 cycles of therapy. Most patients experienced a significant decrease in PSA, some had tumors shrink on scans, and severe side effects were limited.

We have previously published on the (initially) surprisingly high frequency of inherited “germline” alterations in men with advanced prostate cancer. A Spanish group performed a prospective study of 419 men and found that about 9% had alterations in genes that affect the body’s ability to repair damaged DNA. Among the 6.2% with the most common alterations – BRCA2, ATM, and BRCA1  — overall survival was not significantly shorter compared to men without these genetic mutations. However, when examining just the most common BRCA2 gene, men did not live as long. Whether or not these inherited DNA alterations were present, men could respond to approved therapeutic agents, so if clinical trials are not available men should be encouraged to take standard hormonal or chemotherapy.

AACR 2017

AACR 2017April brings more than just showers – the month kicks off with a very important cancer research conference. Tomorrow we are headed to Washington, DC for the American Association for Cancer Research (AACR) annual meeting held April 1-5, 2017.

Our team will be joining approximately 20,000 cancer researchers from across the country and around the world for this important meeting. Several physicians and scientists from Weill Cornell Medicine, NewYork-Presbyterian, and the Meyer Cancer Center again served on the scientific program committee, including our own Dr. Scott Tagawa.

We’re also proud that Dr. Bishoy Faltas was selected as an AACR NextGen Star, a competitive award that supports professional development and advancement for scientists who are early in their career. Dr. Faltas will be presenting important updates related to bladder cancer, and his NextGen Star talk will take place on Wednesday, April 5, and is titled Genomic dissection of the clonal evolution dynamics of chemotherapy-resistant urothelial carcinoma.

We have a lot to share at AACR 2017, so please check back frequently as we’ll be updating the blog regularly throughout the week.

Here are some additional highlights of what’s to come:

  • Updates regarding circulating tumor cells (CTCs) and the role of biomarkers in non-invasive diagnostics and treatments
  • How organoids may help us better treat neuroendocrine prostate cancer (NEPC)
  • The different types of radiation used to treat prostate cancer and how we’re targeting PSMA – a marker on the surface of most prostate cancer cells – with radioimmunotherapy to kill cancer cells
  • The latest updates in bladder cancer research, including updates in genomics and targeting molecular pathways

Using Radiation, Radioimmunotherapy and Radioactive Isotopes such as Lutetium 177 to Treat Prostate Cancer

Radiation is a mainstay in the treatment of prostate cancer. In men with localized prostate cancer (confined to the prostate gland), using radiation can help cure the cancer. In men with advanced disease, radiation can improve survival and help to manage pain.

Radiation can be delivered a variety of different ways. For example, there are external beams that can be used to deliver radiation from an external machine into the prostate, radioactive “seeds” that can be implanted, or ways to inject special radioactive isotopes directly into the bloodstream.

In the United States (U.S.), there are older FDA-approved treatments utilizing radioactive isotopes for men with prostate cancer that has spread to the bones to decrease pain, called samarium-153 (brand name Quadramet) and strontium-89 (Metastron). More recently, a bone-targeted alpha particle called radium-223 (brand name Xofigo®) was approved because it leads to longer overall survival in men with symptomatic metastatic castration-resistant bone metastases. These bone-targeted radioisotopes have been useful because prostate cancer commonly spreads to bone. However, those drugs cannot treat other sites of tumors such as in the prostate, lymph nodes, or lung.

We are also able to use parts of the immune system as a way to deliver radioactive particles or other targeted cancer treatments to the prostate cancer. We have engineered very specific monoclonal antibodies and molecules that will bind only to PSMA, leading to the opportunity for “molecularly targeted” radiotherapy for prostate cancer. When we combine immunotherapy with monoclonal antibodies with radioactive isotopes, we call the treatment approach radioimmunotherapy. Radioimmunotherapy involves attaching a radioactive isotope (such as Lutetium 177) 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 serves as a key that will only recognize a very specific lock (the cancer-related molecule). In prostate cancer, nearly all cells have a specific “lock” that lives on the surface of each cell called prostate-specific membrane antigen (PSMA).

j591_psmaFor nearly 15 years, we have been utilizing a monoclonal antibody known as J591, which is a version of a specific key that will only recognize and enter cells with the specific lock PSMA. We successfully utilized this antibody tagged with small radioactive particles to either visualize or treat prostate cancer tumors within the prostate, bone, lymph nodes, and other sites in the body. Our initial studies demonstrated safety and signaled anti-tumor efficacy. In addition, we showed that the antibody went to virtually all sites of tumors (sometimes discovering new ones) and did not target other normal organs (with the exception of the liver which helps clear the drug from the body). Subsequently, our larger studies have shown responses in larger numbers of patients. In Europe, physicians picked up on our results and Lutetium 177 (also known as Lu-177, 177-Lu or 177 Lutetium) has become a very popular radioactive particle that can be directed to prostate cancer via PSMA. It has been used to kill prostate cancer cells and treat hundreds of prostate cancer patients. This commonly-used approach uses a small molecule which recognizes PSMA to deliver Lu-177 to prostate cancer cells (termed radioligand therapy or radioimmunotherapy therapy).

Lutetium-177 PSMA therapy is associated with a good prostate cancer response and many men travel from all over the world to Europe in order to access this treatment. In the U.S. it is only available via clinical trials, and for more than 10 years, Weill Cornell Medicine and NewYork-Presbyterian have been one of the few centers in the U.S. to offer Lutetium 177 and other targeted treatments using radioactive particles.

Learn more about how this treatment works in this video: