Success of Abiraterone Trials Prompts ‘Mind Shift’ in Prostate Cancer Treatment

The below has been adapted and excerpted from an article in Healio in which Dr. David Nanus HeadshotNanus comments on The LATITUDE and STAMPEDE trials — results of which were presented at this year’s ASCO Annual Meeting and subsequently published in The New England Journal of Medicine. Read the full story here.

Abiraterone acetate is poised to challenge docetaxel as the standard addition to androgen deprivation therapy for treatment of newly diagnosed, metastatic castration-resistant prostate cancer. The LATITUDE and STAMPEDE trials showed the addition of abiraterone acetate and prednisone to androgen deprivation therapy (ADT) reduced risk for death by nearly 40%.

Docetaxel — an IV chemotherapy — can cause nausea, constipation, diarrhea, neutropenia or fatigue during its 18-week dosing schedule. Abiraterone, an oral adrenal inhibitor traditionally used in later-line therapy, is administered until disease progression and has relatively few side effects.

Docetaxel became the standard of care in patients with metastatic hormone-resistant prostate cancer following results from the CHAARTED study, published in 2015 in The New England Journal of Medicine. The results, based on median follow-up of 28.9 months, showed docetaxel improved median overall survival (OS) from 44 months to 57.6 months.

Abiraterone typically has been reserved as second-line therapy for men resistant to ADT. The LATITUDE and STAMPEDE trials — both supported by Janssen, the manufacturer of abiraterone — evaluated whether abiraterone would be more beneficial if used earlier.

Although abiraterone conferred unprecedented survival benefits and is better tolerated, not all oncologists agree it should replace docetaxel in the absence of a head-to-head comparative trial.

HemOnc Today asked urologic oncologists and researchers about the promise of abiraterone; the potential impact of its long-term use; if its cost in comparison with docetaxel is prohibitive; and whether abiraterone soon will be challenged by other therapies for the treatment of metastatic hormone-resistant prostate cancer.

“Abiraterone is a whole new paradigm because your patient is not coming in for an infusion every few weeks for six cycles,” David M. Nanus, MD, professor of medicine and urology at Weill Cornell Medicine, told HemOnc Today. “With six cycles of docetaxel, patients are often wiped out by the time they’re done, and it might take a few months to recover afterward.”

Based on the findings of the LATITUDE and STAMPEDE trials and the potential of targeted therapy, oncologists with whom HemOnc Today spoke agreed researchers are on the precipice of significantly extending the lives of men with prostate cancer.

In addition to the enthusiasm surrounding abiraterone and its potential to be the new standard of care in the treatment of metastatic, castration-resistant prostate cancer, several ongoing clinical trials are investigating other strategies to reduce androgen exposure. Results of those trials also could be practice changing, and again raise questions about the standard of care.

 

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.

Get Ready for ESMO 2017

The start of fall is here and with the foliage comes a very busy conference season. Up first, we are headed across the ocean to Madrid, Spain for the European Society for Medical Oncology (ESMO) annual meeting from September 8 – September 12.

ESMO LOGO

Our team will be joining nearly 23,000 cancer researchers from 131 countries for this important meeting highlighting the groundbreaking research in cancer. Some of our physicians and scientists from Weill Cornell Medicine and NewYork-Presbyterian will be attending and presenting their research in prostate, bladder, and kidney cancer.

We have a lot to share at ESMO 2017, so please follow along on our social media channels and blog for more updates throughout the weekend and next week.