The pharmaceutical company Exelixis has announced that their experimental treatment, cabozantinib has failed the Phase III clinical trial for men with metastatic castration-resistant prostate cancer (mCRPC). In the trial the experimental treatment cabozantinib was compared to the drug prednisone.
In the trial known as COMET-1, Cabozantinib, a tyrosine kinase inhibitor, did not meet its primary endpoint of demonstrating a statistically significant increase in overall survival (OS) for men compared to prednisone. The trial compared the effectiveness of cabozantinib and prednisone in 960 men with mCRPC whose disease progressed after treatment with docetaxel as well as abiraterone and/or enzalutamide.
Men were randomized 2:1 to receive cabozantinib (60 mg daily) or prednisone (5 mg twice daily). COMET-1 yielded a median overall survival (OS) for men treated with cabozantinib of 11 months, compared with 9.8 months for the prednisone arm, which was not statically significant. Median progression-free survival (PFS) was 5.5 months for the cabozantinib arm.
Joel T. Nowak, M.A., M.S.W.
I recently was informed that I am the co-recipient of the Harry Pinchot Award from the Prostate Cancer Research Institute. The award recognizes outstanding dedication and support to the prostate cancer community and I am pleased and very flattered to be one of this year’s receptients.
I have been told that one reason I have received this award is because of the overwhelming support that many of my blog readers demonstrated in support of my nomination. I wanted to take this opportunity to thank all of you who actively supported my nomination.
The award will be formally presented to me in Los Angeles on Saturday, September 6th at the Gala Ball during the upcoming PCRI patient conference.
I want to thank all of you for supporting me in my efforts and more importantly for continuing to support each other as we go on this journey together.
I have written a very special “call to action” as a brief acceptance speech and I will publish it on the blog after the 6th.
Again, thank you for your support.
Advanced prostate cancer and its treatments has significant impacts on a man’s quality of life (QOL) as well as their perception of their health. It is important to better understand these concerns, especially those currently not captured by the currently available health-related quality of life (HRQL) instruments.
In the quest to better understand these concerns researchers conducted interviews with prostate cancer survivors who had either a biochemical failure or metastatic cancer. Their goal was to understand the impacts of disease and treatments on these survivor’s perceptions of their lives. They conducted open-ended one-on-one interviews with 25 survivors (7 biochemical failure and 18 metastatic).
Survivor responses were analyzed to assess whether currently available QOL instruments adequately measured the survivor’s concerns. The data informed the development of a comprehensive conceptual model illustrating the impacts of advanced disease and treatments.
The interviewed survivors reported many of the key symptoms already captured by current measures such as bone pain, urinary functioning, bowel functioning, and fatigue. However, a number of impacts reported as bothersome by the survivors were identified that are not fully captured by existing measures. Specific examples include genital atrophy, muscle atrophy, stamina, body image, and emotional well-being.
Increasing clinicians are becoming aware of the importance of survivorship care for cancer survivors. This is one step n many needed steps in helping our treating physicians understand our concerns so they might be able to better help us get the treatments and therapies we need to improve our time as survivors.
Oliver Sartor, Emuella Flood, Kathleen Beusterien, Josephine Park, Iain Webb, David MacLean, Bruce J.O. Wong, H. Mark Lin
Joel T. Nowak, M.A., M.S,W.
Abiraterone acetate (AA) or Zytiga has demonstrated a survival benefit in the pre-chemotherapy setting for men with advanced prostate cancer that has become castrate resistant (mCRPC). As a result it is in widespread clinical use in the United States prior to the use of chemotherapy with docetaxel. Since its FDA approval post chemotherapy there has developed increasing interest in utilizing enzalutamide (Xtandi) in this same space, prior to chemotherapy.
However, there remains a lack of data on what might be the impact of therapy with Zytiga have on the efficacy of Xtandi or docetaxel if later given. Considering that Xtandi will probably also receive FDA approval in this prechemotherapy space as well as the developing trend to use it off lable in this space there is a very real need to know this information.
Researchers at Duke University looked at this issue. They took a sampling of men with mCRPC treated Zytiga prior to chemotherapy or Xtandi, either on a trial or in standard practice. Clinical and demographic information, laboratory values, response, and progression and overall survival-based outcomes were also abstracted.
The men were separated into two main groups: group A, who were treated with Zytiga followed by Xtandi and group B, who were treated with Zytiga followed by docetaxel-based chemotherapy.
The primary objective was to describe response and progression free survival to subsequent therapy after progression on Zytiga.
Group A (Zytiga then Xtandi, n=8), and group B (Zytiga then docetaxel, n=12) had similar clinical characteristics at progression, including pain and patterns of spread. However, group A had higher baseline circulating tumor cell (CTC) and prostate specific antigen (PSA) levels then , group B, who were younger (mean 65 vs 73 yrs).
The research found a clear cross-resistance in the majority of men with mCRPC, while docetaxel provided a greater probability of PSA decline and radiographic/clinical benefit then the Xtandi group after Zytiga exposure. If you have had Zytiga discuss with your doctor the possible advantage of next using chemotherapy as opposed to Xtandi.
These data may help to inform on the complex treatment decisions facing men with mCRPC progressing on first line Zytiga and should be explored in larger multicenter registries and controlled trials.
J Clin Oncol 32, 2014:Tian Zhang, Mallika S. Dhawan, Patrick Healy, Daniel J. George, Jorge Oldan, Bennett Chin, Andrew J. Armstrong
Joel T Nowak, M.A., M.S.W.
Clouded in the murkiness of the debate surrounding the use of the PSA test is an increasing escalation of younger men (under the age of 50 years) being diagnosed with advanced prostate cancer. We know that there has been escalating incidence rate (IR) of prostate cancer PC noted in the last two decades. Many have attributed this IR to the more common use of PSA testing for early PC detection.
Researchers performed a study to compare the relative and absolute rates of detection of early and advanced PC in younger males under the age of 50 and to examine if early cancer was the only contributor to the change in this group.
They used frequency and rate sessions on demographics and PC characteristics comparing among Non-Hispanic White (NHW), African-American (AA), Hispanic (H), US Asian/Pacific Islanders (A/PI) and American Indians/Alaskan Natives (AI/AN) using SEER*Stat. They then used the IR and stage at diagnosis trends of subjects diagnosed under the age of 50 years.
They found that a total of 22,227 cases of PC were reported under the age of 50 years at diagnosis in SEER database from 1973-2010. About 77% were in NHW, 12% in AA, 6% in Hispanics, 4% in A/PI and less than 1% in AI/AN. Table below reflects our results.
They found that IR of PC increased significantly in men under the age of 50 years in the last decade. However stage breakdown did not change significantly. This implies that incidence of advanced stages prostate cancer escalated in parallel with early stages.
This increase can’t be fully explained by the use of PSA screening.
The question then becomes why have we seen this increase? Possibly there are some unknown epigenetic, environmental or socioeconomic factors contributing to this increased risk of advanced prostate cancer in younger men. . Relative increase in IR was especially high in S Asian/Pacific Islander population (by 125%) with a trend towards increase of advanced stage cancer share (by 3%). Further studies into PC risk factors are warranted.
J Clin Oncol 32, 2014 (suppl; abstr e16030); Uladzislau Naidzionak, Katsiaryna Ivanova, Akm Mosharraf Hossain
Joel T. Nowak, M.A., M.S.W.