Treating Advanced Prostate Cancer and Kidney Cancer: Research from the 2019 Genitourinary Cancers Symposium

Genitourinary Cancers Symposium
February 11, 2019
Greg Guthrie, ASCO Staff

The 2019 Genitourinary Cancers Symposium will be held February 14 to 16 in San Francisco, California. This multidisciplinary conference draws experts from all over the world to discuss new ways to improve the lives of people with genitourinary cancers, such as kidney cancer and prostate cancer.share on twitter

You can learn more about research from this symposium by following the #GU19 hashtag on Twitter.

Below are summaries of 3 studies that will be presented at the symposium:

  • African-American men with advanced prostate cancer live longer than white men when treated with newer hormone therapies

  • Metastatic castration-resistant prostate cancer has a high response rate to radiolabeled targeted drug

  • Combined pembrolizumab and axitinib helps people with advanced kidney cancer live longer

African-American men with advanced prostate cancer live longer than white men when treated with newer hormone therapies

An analysis of 5 years of data from the U.S. Veterans Health Administration (VHA) found that African-American men with metastatic castration-resistant prostate cancer (mCRPC) lived about 4 months longer than white men if they had not been treated with chemotherapy and received either abiraterone acetate (Zytiga) or enzalutamide (Xtandi).share on twitter Both of these drugs are a type of hormone therapy called an anti-androgen. mCRPC is advanced prostate cancer that has continued to grow and spread despite treatment to lower testosterone levels.

The researchers analyzed data from the VHA database from April 2013 to March 2018. They studied men who had only been treated with androgen-deprivation therapy (ADT), also called hormone therapy or castration. ADT can involve surgery to remove the testicles, which is called bilateral orchiectomy. Or it can involve treatment with medicine, such as luteinizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists, and anti-androgens. Among the men with prostate cancer that progressed after ADT, the researchers then further searched for men who received abiraterone acetate or enzalutamide. This analysis included data from 2,123 white men and 787 African-American men with mCRPC, with average ages of 74 for white men and 71 for African-American men. The African-American men had more high blood pressure, type 2 diabetes, and liver problems than the white men.

In this study, the data showed that African-American men who were treated with either abiraterone acetate or enzalutamide lived for a median of 30 months, about 2.5 years. The median is the midpoint, meaning that half of the men lived less than 30 months and the other half lived longer than that. For white men treated with either of the drugs, the median survival was 26 months, which is a little over 2 years. These results were adjusted for demographic and clinical characteristics found in the VHA database.

Recent studies presented at the 2018 ASCO Annual Meeting also showed that African-American men with prostate cancer lived longer than white men if they were treated with docetaxel (Taxotere) and abiraterone acetate. African-American men are more likely to develop the disease when they are younger and the tumors may be more aggressive. In general, African-American men are also more likely to die from prostate cancer than white men. Research is ongoing to find out more about the biology that drives these racial differences in prostate cancer, with the goal of improving treatments and understanding why African-American men have a higher incidence of the disease.

What does this mean? The anti-androgens abiraterone acetate and enzalutamide work better in African-American men, even though they are known to be at a greater risk of dying from prostate cancer. There are unknown biological reasons for these racial differences in prostate cancer, and researchers are working to learn more.  

“We’ve historically seen that prostate cancer is more common, more aggressive, and more lethal in African Americans, compared with men of other racial groups. Despite having more non-cancer related health complications, we found that treatment with newer hormonal medicines led to a significantly greater survival for African-American men in this analysis, compared with white men.”

—   lead study author Megan McNamara, MD
Duke University School of Medicine
Durham, North Carolina

Metastatic castration-resistant prostate cancer has a high response rate to radiolabeled targeted drug

A study of 50 men with mCRPC found that treatment with a radioactive targeted drug was very effective and lengthened lives for a median of around 13 months. A median is the midpoint, meaning that half of the results are on each side of the median. All of the men in this clinical trial had mCRPC that had prostate specific membrane antigen (PSMA) on the surface of the cancer cells. PSMA can indicate the aggressiveness of the prostate cancer. PSMA can be detected using positron emission tomography (PET) scans.

The drug in this clinical trial is called lutetium-177 PSMA-617 (LuPSMA). LuPSMA seeks out cancer cells with high levels of PSMA on the surface and then delivers radiation to those cells in order to destroy them. The radiation is delivered by the lutetium-177, a radioisotope that releases beta radiation, which can destroy cancer cells, and gamma rays, which can be seen using PET scans. During treatment, PET scans can be used to find out if the treatment is stopping or shrinking tumors. With this approach, LuPSMA delivers high doses of radiation directly to the cancer cells and lessens the potential damage to normal cells. A broader term to describe this type of treatment is peptide receptor radionuclide therapy (PRRT).

The men in this study were between 50 and 87 years old and had rapidly doubling prostate-specific antigen (PSA) levels, a sign of aggressive disease. The prostate cancer was not stopped by treatment with chemotherapy or anti-androgens. LuPSMA was given intravenously (into the veins of patients) for up to 4 cycles every 6 weeks. Researchers used PSA levels and PET scans to check whether the treatment was working. If the cancer continued to grow and spread, more cycles of LuPSMA were given.

In 32 of the 50 men, PSA levels were lowered by 50% or more. In 22 men, the PSA level reduction was 80% or more. PSA levels did not increase in these men for a median of nearly 7 months, indicating that the treatment had stopped the cancer. For 14 men, the cancer continued to grow and spread after treatment, and they received a median of 2 more cycles of LuPSMA. Of those 14, 9 men saw their PSA levels lower by 50% or more. Those 9 men who received additional treatment lived for a median of 33 months. 

The most common side effects were dry mouth, nausea, and fatigue. This is because PSMA is also found on cells in the salivary and tear glands. About 10% of the men had more serious side effects, including anemia and low blood platelet counts, also called thrombocytopenia.

What does this mean? Delivering radiation precisely to specific cells is an effective way to target cancer and limit damage to normal cells, especially for difficult-to-treat mCRPC. For people with prostate cancer cells that express PSMA, LuPSMA may become a new treatment option.share on twitter

“It’s exciting to see that LuPSMA can potentially offer benefits for many men with these very aggressive cancers, with few side effects and significant improvements in quality of life. Importantly, we saw continued benefits with LuPSMA treatment in some men whose cancer progressed.”

—   lead study author Michael Hofman, MD
Peter MacCallum Cancer Centre
Melbourne, Australia 

Combined pembrolizumab and axitinib helps people with advanced kidney cancer live longer

Results from the phase III KEYNOTE-426 global clinical trial found that pembrolizumab (Keytruda) plus axitinib (Inlyta) may be more effective than sunitinib (Sutent) as a first treatment for kidney cancer that has spread to distant sites, called metastatic. The type of kidney cancer studied in this clinical trial was clear cell renal cell carcinoma (RCC), which is the most common type of kidney cancer. Pembrolizumab is a type of immunotherapy called an immune checkpoint inhibitor that targets a protein called PD-L1. Axitinib and sunitinib are a type of targeted therapy for kidney cancer called tyrosine kinase inhibitors that block a protein called VEGF.

Combining immunotherapy with targeted therapy is a new approach to treatment for this type of cancer.share on twitter When given alone, targeted therapy and immunotherapy tend to work in about a third of people with kidney cancer. In an earlier phase of this clinical trial, researchers saw that a combination of targeted therapy and immunotherapy caused tumors to stop growing or shrink in 70% of patients. The goal of this phase III clinical trial was to see if the combination treatment helped people live longer and was safe to use.

This study included 861 people with metastatic clear cell RCC who had not received any previous systemic treatment, with 432 receiving pembrolizumab plus axitinib and 429 receiving sunitinib alone. The average age of the people was 62 years, and 70% of them were men.

After a median of about 13 months of follow-up, nearly 60% of patients were still receiving the combination treatment, compared with about 43% of patients still receiving sunitinib alone. At 1 year, nearly 90% of the patients taking the combination treatment were still alive, compared with about 78% of the patients taking sunitinib. Those taking the combination treatment had their disease stopped for a median of 15 months, compared with a median of 11 months for those taking sunitinib alone.

All of these drugs come with risks of serious side effects. This study only included people whose health was measured to be strong enough to receive the drugs. Serious side effects developed in nearly 63% of those taking the combination and 58% of those taking sunitinib.  And, 6% had to stop the combination treatment because of side effects and 10% had to stop taking sunitinib.

What does this mean? This combination of immunotherapy and targeted therapy may offer a new approach to initially treating metastatic clear cell renal cell carcinoma. Patients should talk with their doctor about the risk of side effects before starting immunotherapy or targeted therapy.

By adding pembrolizumab to a VEGF-targeted therapy, we are seeing powerful anticancer responses, including improved survival—and importantly, the results are seen in broad groups of patients.

—   co-lead study author Thomas Powles, MD
Barts Cancer Institute
London, United Kingdom

 

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