Tag: Prostate Cancer

Best of ASCO 2016: Prostate Cancer Treatment Updates

Beltran_HeadshotLast weekend, Dr. Himisha Beltran traveled to Washington, D.C. to speak at the “Best of ASCO” meeting. She hosted the session on prostate cancer and summarized some of the most important studies presented at the 2016 American Society of Clinical Oncology (ASCO) meeting in Chicago.

She also represented Weill Cornell Medicine and NewYork-Presbyterian on a panel of the nation’s leading experts. The panel answered questions regarding some of the most challenging cases in genitourinary (GU) cancer care.

What’s new in research and treatment?

For men with advanced (metastatic) prostate cancer, the class of chemotherapy that has consistently proven to improve survival is called “taxanes.”

There are two taxanes that have been FDA-approved to treat prostate cancer, docetaxel (brand name: Taxotere) and cabazitazel (brand name: Jevtana). While these drugs are similar, men whose tumors have grown despite taking one drug often respond to the other.

Much of the important research at this year’s ASCO meeting focused on some key questions related to these two treatment options:

1. What treatment dose is best to maximize response, but minimize side effects?
2. Does the order in which patients receive these treatments matter?
3. When should oncologists switch between treatments if one is not working?
4. What is the impact on quality of life?

Another hot topic was the value and cost of treatments, and the link between treatment cost and access to care, since there can be financial barriers associated with certain treatments.

Below, we’ve outlined some of the key studies and clinical takeaways for prostate cancer treatment that Dr. Beltran discussed at the Best of ASCO meeting:

Chemotherapy Updates
  • For patients with untreated metastatic prostate cancer, large studies have recently demonstrated the improved survival impact of using a combined treatment of both chemotherapy and hormonal therapy as opposed to only hormonal therapy for men with metastatic prostate cancer. A new research study examined the CHAARTED study data and evaluated the quality of life (QOL) of patients treated on the study. This research found that while the QOL was initially worse (at 3 months), there was no long-term negative impact, and QOL was better at 12 months for chemo patients relative to those who only received hormonal therapy. This has important implications for counseling patients, as some are worried about side effects. It is comforting to know that while side effects may occur, they are temporary and the longer-term benefit of cancer control leads to improved QOL in the longer term.
Radiation Updates
  • A randomized trial examined radiation therapy for treating localized prostate cancer that had not spread beyond the prostate gland in men with intermediate risk disease. This study compared the standard eight-week course of treatment with a shorter course of four weeks, called hypofractionation. The shorter course of treatment did not see any reduction in treatment response and did not increase toxicity. The results from this study in combination with two other similar studies (RTOG 0415 and ChIPP) support using hypofractionation as a new standard for men with intermediate risk prostate cancer, as it is more convenient since it requires fewer visits to complete and is potentially less costly for patients.
Genomic Updates
  • In a large multi-institutional study of nearly 700 patients (including Weill Cornell), over 11% of patients with metastatic prostate cancer had inherited mutations in DNA repair genes (such as BRCA2 or ATM). This has important family risk and treatment implications since these genes can be passed down through the family tree and are not only linked with prostate cancer, but other cancer risk, as well. This is practice changing and supports genetic counseling and testing for all men with metastatic prostate cancer. In addition, research is ongoing to utilize drugs that may work especially well in this situation.

Hi-Tech Blood Biomarker Signals When a Strategic Switch in Chemotherapy Will Benefit Prostate Cancer Patients

For men with metastatic prostate cancer that grows despite hormonal therapy (also referred to as castration-resistant prostate cancer), chemotherapy has been a mainstay. The class of chemotherapy that has consistently proved to improve survival for men with advanced prostate cancer is called “taxanes.”

Taxanes target microtubules, which are structures in cells that are involved in cell division, as well as the trafficking of important proteins. In prostate cancer, one of the main ways taxane chemotherapy works to kill the cancer cells involves blocking the movement of the androgen receptor (AR) along the microtubule “tracks” towards the cell nucleus, a mechanism we discovered here at Weill Cornell Medicine.

There are two taxanes FDA-approved to treat prostate cancer, docetaxel (brand name: Taxotere) and cabazitazel (brand name: Jevtana). While the drugs are similar, men whose tumors have grown despite taking one drug often respond to the other. The challenge for oncologists has been pinpointing when exactly to switch treatments.

ScottTagawa_ASCO2016_TAXYNERGYDr. Scott Tagawa presented exciting results from a phase II clinical trial at the 2016 American Society for Clinical Oncology (ASCO) annual meeting demonstrating the power of this treatment switch, and when to make the switch.

This research came to be because we thought that we might be able to increase the number of men who respond to taxane chemotherapy with an early assessment and by changing the drug for those who have a sub-optimal response. Simply put, those with no response or only an initial minor response had their drug changed at a much earlier time point then standard practice. This resulted in a higher response rate for the patients in the study.

Top Boxes_Taxynergy
In the photos from a sub optimally responding patient, almost all of the androgen receptor (AR, labeled in green) is in the nucleus (indicated by the arrow which is overlayed in blue on the right), meaning that the taxane chemotherapy treatment was unable to block AR from moving to the nucleus and thus unable to kill the prostate cancer cells.

In addition, it’s very exciting that we can examine cancer cells from a simple blood test, a process also referred to as collecting circulating tumor cells or CTCs. This allows us to assess the ability of a drug to target the pathway in real time and to tell us whether there is a positive tumor response or resistance.

These circulating tumor cells provide an opportunity for real-time molecular analysis of taxane chemotherapy and at Weill Cornell Medicine we’ve pioneered a way to examine the AR pathway with a simple blood test.

To do this we use an extremely specialized technology that captures the very small fragments or rare circulating tumor cells on a “chip.” From this chip we are able to determine which cells are responding to treatment.

Bottom Boxes_Taxynergy
In real time, we can see taxane chemotherapy kept the (green) AR out of the (blue) nucleus area in cells from a responding patient. 

In cancer care, we are always trying to maximize treatment response rates by targeting the right cells at the right time. This promising precision medicine approach offers us one more tool to better personalize treatment and improve outcomes.

 

Dr. Tagawa Presents Updated Results of ATL101 at AACR

At the annual American Association for Cancer Research in Washington, DC last week, Dr. Scott Tagawa presented updated combined analysis of 4 Phase I and Phase II studies involving 114 patients treated with ATL101. The analysis demonstrated that PSMA imaging might be used to predict the response to ATL101 radioimmunotherapy.ATL101 is a new targeted radiotherapy experimental drug for treating prostate cancer. ATL101 combines the humanized J591 monoclonal antibody targeting prostate-specific membrane antigen (PSMA) plus the Lutetium-177 radioisotope, creating the first tumor-specific delivery system able to target radiation to radio-sensitive prostate cancer cells wherever they are in the body.

From the sponsor’s press release:

14 patients were evaluable for semi-quantitative analysis of planar gamma images acquired after injection of ATL101 (35 patients from phase I at dose of 10-75 mCi/m²; 47 patients from Phase II at dose of 65-70 mCi/m² and 39 patients from phase I with a fractionated schedule at dose of 40-90 mCi/m²). 22 patients were also evaluable after injection of Indium-111 labeled J591 and treatment by Yttrium-90 labeled J591 at dose of 5-20mCi/m². Patients were sorted into 3 groups: low PSMA expression group included one third of patients, with no uptake (18%) or with weakly positive images (16%); high PSMA expression group included one half of patients, with tumor image as intense (26%) or more intense (24%) than liver. The 16 % remaining patients had intermediate uptake.

Significant correlation was found between higher PSMA expression (high vs. low) and higher response rates (RR) to treatment defined as >30% decline in PSA (RR=32% vs. 12.5%, p=0.01). RR was itself significantly correlated to longer survival. An association between PSMA expression by imaging and reduction in circulating tumor cell counts was also found (p=0.07). Further studies will examine quantitative molecular imaging with anti-PSMA PET/CT as recently published in animal models (Morris et al, 2013 ASCO Genitourinary Cancers Symposium).

Click here to read the complete press release.