ASCO 2017: Genitourinary (GU) Oncology Highlights

ASCO Logo PhotoEach year, the American Society of Clinical Oncology (ASCO) Annual Meeting brings together more than 30,000 oncology professionals. At this year’s meeting in Chicago, physicians and scientists presented the latest research findings in an effort to bring the best cancer treatments to patients across the United States and the world. We’ve outlined some of the genitourinary (GU) oncology highlights, broken down by disease type.

At this year’s meeting, there was also some important research presented related to communication, quality of life and survival. In a study that involved patients with GU cancers, as well as those with other types of tumors, patients were randomized to two groups: 1) a control group of standard care 2) a group to utilize a web-based patient-reported outcome questionnaire between visits. Results from any answers completed in the online system were sent to the treatment team in real time. In this study, the patients that were randomized to the online questionnaire group experienced better quality of life. In addition, these patients lived longer, with a 17% improvement in survival simply by using the online tracker reporting symptoms to their treatment team between visits. While the study was only conducted at a single institution, it underscores the importance of communicating and relaying any symptoms to your treatment team members responsible for your medical care (generally physicians, nurses and advanced practitioners).

Prostate Cancer:

The results from two large phase 3 clinical trials will lead to a change in the standard of care treatment for men with advanced prostate cancer. The LATITUDE and STAMPEDE trials investigated the addition of abiraterone and low dose prednisone to standard androgen deprivation therapy (ADT) for men with advanced prostate cancer. Similar to the unprecedented results presented at ASCO in 2014 (CHAARTED) and 2015 (STAMPEDE) with the use of docetaxel chemotherapy, a major improvement in overall survival was demonstrated, improving length of life by nearly 40%. The results from these studies will provide an additional treatment option for men presenting with advanced prostate cancer.

For men with metastatic castration-resistant prostate cancer (mCRPC), a randomized phase 2 trial demonstrated no significant differences in the efficacy, or effectiveness, of abiraterone or enzalutamide, two of the leading treatments for prostate cancer that is resistant to hormonal therapy. This research finding was consistent with most clinicians’ belief that either drug may be utilized, allowing physician and patient choice. Importantly, the study incorporated a number of interesting biomarkers using circulating tumor cell (CTC) DNA from a liquid biopsy, and the data gleaned from the DNA revealed prognostic insights about disease aggressiveness and biology. Another study showed a lack of utility to continue enzalutamide after disease progression, confirming the current practice of switching treatments after cancer growth.

Interesting data using the PARP inhibitor veliparib was presented. In a randomized phase 2 trial, the combination of veliparib and abiraterone was not better than abiraterone alone overall, but for tumors with DNA damage repair defects, there was a difference. This adds to the anticipation of results from the many ongoing randomized trials that are testing PARP inhibitors in molecularly selected patients.

Additional data was presented on genomic signatures from prostate tissue, which in combination with clinical data, are more powerful in indicating prognosis in men who receive treatment for clinically localized (low stage / early) prostate cancer.

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Dr. Himisha Beltran

Prostate cancer acquires resistance to systemic treatment as a result of tumor evolution and selection, but repeat biopsies to study how cancers evolve are challenging, invasive, and may be confounded by tumor heterogeneity. Dr. Himisha Beltran evaluated a non-invasive approach: whole exome sequencing of circulating tumor DNA in the blood. Additional data utilizing circulating tumor cell (CTC) counts as an early indicator of response may speed drug development. Clinical trials are currently evaluating measuring circulating tumor cell counts as a biomarker for whether or not treatments are working. This may be a better indicator than measuring levels of prostate specific antigen (PSA), the current indicator for response.

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Dr. Scott Tagawa presents an update on the 177Lu-PSMA-617 clinical trial for men with metastatic prostate cancer.

Dr. Scott Tagawa presented a trial-in-progress update about the clinical trial he is leading at Weill Cornell Medicine and NewYork-Presbyterian utilizing the small molecule lutetium 177Lu-PSMA-617 to target prostate-specific membrane antigen (PSMA). PSMA is a protein abundantly expressed in 85-90 percent of metastatic prostate cancer cells, and this is the first U.S. trial of its kind. Learn more about this radionuclide therapy-based clinical trial and the eligibility criteria.

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Dr. Loredana Puca

Additionally, there were many research updates presented in the area of neuroendocrine prostate cancer (NEPC), an aggressive subtype of prostate cancer that is resistant to many traditional treatment types. Dr. Loredana Puca received a Merit Award from the Conquer Cancer Foundation for her research examining the potential use of antibody-drug conjugate rovalpituzumab tesirine for treatment of NEPC. View the abstract and learn more about our open clinical trial using this antibody-drug conjugate. Dr. Himisha Beltran highlighted the significance of the loss of tumor suppressor ZFP36 in prostate cancer patients.

Prostate cancer was the first tumor type to have a cancer vaccine (sipuleucel-T) lead to longer survival, but the drug’s activity may be limited on its own. In a randomized phase 2 trial, receiving sipuleucel-T in combination with indoximod – a drug with the potential to improve immune response – kept the cancer at bay more than twice as long compared to those who received sipuleucel-T plus a placebo. This was an exciting research update showing promise for patients with prostate cancer.

New research using tumor and liquid (blood-based) biopsies demonstrated that a majority of tumors and circulating tumor cells in men with metastatic castration-resistant prostate cancer express a protein called Trop-2, justifying a targeted treatment approach. With this knowledge, we are now evaluating the safety and efficacy of IMMU-132, an immunotherapy-based drug that targets Trop-2, in an open clinical trial for men with prostate cancer.

Bladder Cancer and Other Urothelial Cancers:

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Dr. Bishoy Faltas presents on “Unlocking the Genome: Insights Into Risk and Response in Bladder Cancer” at the ASCO 2017 Clinical Science Symposium.

Dr. Bishoy Faltas was invited to present at the ASCO Clinical Science Symposium entitled “Expanding the Actionable Landscape: Bladder Cancer Genomics — Unlocking the Genome: Insights Into Risk and Response in Bladder Cancer.”

During this session, Dr. Faltas discussed the genomics of urothelial cancer, and highlighted the latest research describing new data on the frequency of inherited (germline) mutations as well as tumor (somatic) genomics and relationship to response to chemotherapy and immunotherapy. Patients with “upper tract” urothelial cancer (tumors arising in the kidney or ureter) in particular have a higher chance of harboring an inherited mutation. Different genomic alterations in the tumors may be separated into groups that are associated with better responses to chemotherapy and immunotherapy. This is becoming more clinically relevant as we can test for these genes and the number of treatment options is expanding.

Additionally, updated results of the KEYNOTE-045 study confirmed the overall survival benefit of the anti-PD1 immune checkpoint inhibitor pembrolizumab (Keytruda) compared to second-line chemotherapy in patients with prior platinum-based chemotherapy. Importantly, this was the first head-to-head trial to demonstrate the superiority of immunotherapy over chemotherapy in urothelial cancer.

Dr. Scott Tagawa contributed to the investigation of a novel oral targeted chemotherapeutic agent called RX-3117 in advanced bladder cancer patients. Learn more about our open clinical trial with RX-3117.

Kidney Cancer (Renal Cell Carcinoma):

Several different combination studies for the treatment of advanced renal cell carcinoma (RCC) were presented at the 2017 ASCO Annual Meeting. While some studies demonstrated promising response data, significant toxicity of some combinations underscored the importance of clinical trials and the recommendation to avoid combinations outside of the research setting, which is regulated and in which these types of side effects can be monitored. Several randomized phase III trials testing combination therapy are ongoing with results anticipated to lead to changes in standard of care.

Unfortunately, despite imaging that indicates no evidence of cancer metastases (spread), many patients are not cured with surgery alone. Treatment of many cancers incorporate the use of systemic (medical) therapy in addition to surgery to increase cure rates. For the most part, this strategy has not been overwhelmingly successful in the setting of renal cell carcinoma (RCC). Unfortunately, another “negative” phase III trial showed that the addition of pazopanib (Votrient) to surgery did not improve cure rates for patients with RCC. Additional data was presented utilizing either clinical or genomic biomarkers that may assist physicians in choosing patients that might benefit from the addition of the oral drugs following surgery. We continue to await the results of additional completed studies and some currently enrolling studies utilizing immunotherapy before/after surgery.

Mini Organs: What Organoids Can Tell Us

Historically, cancer research has been conducted using cell lines that grow in a petri dish. We’ve been able to learn a lot and make much progress in the fight against cancer using this approach, but it also has some limitations, as the environment is not truly reflective of the way cancer cells grow and metastasize within the human body – a three-dimensional (3-D) environment. Additionally, cell lines can mutate over time and then sometimes no longer reflect the genetic and molecular variants of cancer cells.

Over the past 10-15 years, medical research has evolved and grown (literally and figuratively) – what used to only be possible in sci-fi movies and imaginations is now a reality as we create mini-models of bodily organs in the laboratory. These 3-D structures are also known as organoids, and an exciting area of this research is related to cancerous tumors.

Cancer biopsies remove tumor cells directly from the body. Often these biopsies are conducted when a primary tumor is found and removed, and sometimes also if the cancer has grown and spread to other locations throughout the body. This is because tumor cells evolve and change over time, especially as they try to develop workarounds in response to treatment. From the tumor cells that are removed in a biopsy, we’re analyzing the pathology and learning about the cancer on the molecular and genetic level, including any mutations we may be able to target.

Another way we’re able to use these tumor cells is to grow organoids in order to replicate the tumor outside of the body. This 3-D representation of the tumor allows us to conduct research in a way that better addresses the complex structure of the cancer. It is a form of precision medicine or personalized medicine, and allows us to test how an individual patient’s cancer cells may respond to a wide range of treatments.

This video created by the Englander Institute for Precision Medicine provides an overview of how this process works:

Top 5 Diet and Cancer Myths

By Shayne Robinson, RD, CSO, CDN and Jackie Topol, MS, RD, CSO, CDN

RefrigeratorWe know that there is a great deal of conflicting information about nutrition that patients may receive from various sources. As Registered Dietitians who are board certified in oncology nutrition, we are here to clear up some of the confusion. Here are some of the most common nutrition myths we hear from patients:

Myth # 1 – Sugar feeds cancer.

Within the body, all carbohydrates break down to sugar which both healthy and cancer cells use for fuel. Research shows that the body responds to a high sugar intake by making more insulin and related growth factors, which influence cancer cell growth. However insulin levels also depend on genetic factors, physical activity, BMI (body mass index), metabolic syndrome (a group of medical conditions linked to insulin resistance) and the type of sugar you eat. Therefore just avoiding sugar is not the right plan for everybody. It’s important to maintain healthy blood sugar and insulin levels during cancer treatment and in general. In prostate cancer, hormonal therapy is associated with weight gain and the way the body processes sugar, so it’s important to be mindful of this when making dietary choices. Ongoing research is looking to target some of these pathways.

The key question to ask is “How much and what type of carbohydrates should I eat?” A Registered Dietitian who is specially certified in oncology nutrition (RD, CSO) can help you design a well-balanced eating plan that best fits your needs.

Reference: https://www.oncologynutrition.org/erfc/healthy-nutrition-now/sugar-and-cancer/

Myth #2 – I need to avoid raw fruits and vegetables.

Raw fruits and vegetables that have been washed can be eaten while you are receiving chemotherapy and/or radiation. If you have a very low neutrophil count (known as “neutropenia”) or a recent bone marrow transplant, your doctor or dietitian may recommend a low microbial diet. On the low microbial diet, you can eat most raw vegetables and most raw fruits that have a smooth skin or a thick peel. The fruits and vegetables we advise not consuming on the low microbial diet are the ones you cannot wash thoroughly or those that may have mold such as raw mushrooms, sprouts, strawberries, blueberries, raspberries, grapes, peaches, and plums. In the current era of treatment for genitourinary cancers, most targeted therapies do not suppress the immune system or require a low microbial diet. Not all cancer patients will have to follow these guidelines since they are specifically for leukemia and bone marrow transplant patients. If you are not sure whether you should be following a low microbial diet or how long you should follow it for, we encourage you to speak to your doctor or dietitian. Additionally, there are certain oral treatments for kidney cancer that are linked with gastrointestinal side effects such as diarrhea. There are ways to include fruits and vegetables in the diet while taking these factors into account. There are many health benefits that go hand-in-hand with eating fruits and vegetables, so make sure to include them in your diet! If you are concerned that you may not be meeting your nutritional needs, you can make an appointment with one of our dietitians who can help.

Reference: https://www.foodsafety.gov/risk/cancer/index.html and NewYork-Presbyterian’s “Guidelines for the Low Microbial Diet”

Myth # 3 –  Certain foods will increase my white blood cell count.

Chemotherapy drugs, radiation therapy, and cancers of the blood and bone marrow can damage bone marrow and lower white blood cell counts. These cells recover with time.  Blood counts are low because the bone marrow isn’t working properly, not because the body lacks the nutrients to make blood cells.

No specific foods or nutrients increase production of white blood cells, but if you have low blood counts it is very important that you eat well because a well-nourished person recovers quicker from treatment than a malnourished person. Specific foods or nutrients won’t speed up the recovery of your bone marrow, but you do want to eat well so that when your bone marrow recovers all the nutrients that are the building blocks for cells are available for your body to make the white blood cells. A Registered Dietitian specially certified in oncology nutrition (RD CSO) can help you ensure you are eating well and in turn optimize your white blood counts.

Reference: http://www.oncologynutrition.org/erfc/eating-well-when-unwell/white-blood-count-diet/

Myth # 4 – Cancer survivors must eat only organic produce.

Organically grown produce have lower pesticide residues and synthetic (man-made) food additives, but following an organic diet does not guarantee a healthy diet. In fact, avoiding conventionally grown produce may eliminate some healthy food options. In a study looking at 50 years of scientific articles about the nutrient content of organic and conventionally grown foods, the researchers concluded that organic and conventionally grown foods are not significantly different in their nutrient content. There have not been any direct studies on humans to show that organically grown produce can prevent cancer or other diseases any more effectively than conventionally grown foods.

What does this mean in terms of your grocery list? If you go into the market to buy a fresh organic apple, and they only have conventionally grown produce, don’t walk out with a bag of processed organic chips or cookies… A conventionally grown apple is a better choice than organic processed foods.

References:  www.mayoclinic.com/health/organic-food/NU00255
www.foodnews.org  (from the Environmental Working Group)

Myth # 5 – I need to avoid soy foods.

It is safe to eat soy! Research has shown that moderate consumption is safe for women with a history of breast cancer, including women previously diagnosed with estrogen receptor positive breast cancer, and that soy consumption may even decrease the likelihood of breast cancer recurrence. Confusion about soy arises from the term “phytoestrogens.” Some soy nutrients have a chemical structure that look a bit like the estrogen found in a woman’s body. This is where the term phytoestrogen originated. However, phytoestrogens are not the same thing as female estrogens. Soy foods do not contain estrogen. Men with prostate cancer who are taking hormonal therapies also commonly inquire about the impact of eating soy, but again, soy is okay to eat. If you consume soy products, we recommend choosing whole soy foods such as such as soymilk, tofu, tempeh, edamame, soy nuts, and miso. You can have up to two servings per day.  One serving would be 1 cup of soymilk; ½ cup of tofu, tempeh, or edamame; ¼ cup of soy nuts; or 1 tablespoon of miso paste. It is best to get soy directly from foods sources; we do not recommend taking a soy isoflavones supplement.

References: http://www.oncologynutrition.org/erfc/hot-topics/soy-and-breast-cancer/; http://www.oncologynutrition.org/erfc/hot-topics/soy-and-hormone-related-cancers/

Nothing replaces the individualized counseling you will receive from working with an RD on a one-on-one basis. We’re here to help you.

shayne Robinson_head shot 2Shayne Robinson RD, CSO, CDN is an oncology dietitian at New York-Presbyterian.  To make an appointment, call the Outpatient Nutrition Practice at (212) 746-0838 (physician referral required). 

Jackie Topol RD_Headshot_jgt9003
Jackie Topol, MS, RD, CSO, CDN is an integrative dietitian at
Integrative Health at NYP – Weill Cornell Medicine, located at 211 East 80th Street. To make an appointment, please call: 646-962-8690.