Janssen’s Zytiga Approved for Earlier Use in Prostate Cancer

Excerpt:

“European regulators are allowing earlier use of Janssen’s Zytiga in the treatment pathway for metastatic prostate cancer.

“Zytiga (abiraterone) plus prednisone/prednisolone has been approved to treat newly-diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC) in adult men in combination with androgen deprivation therapy (ADT).

“The drug is already available in Europe for metastatic castration-resistant prostate cancer (mCRPC) in adults who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated and in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.”

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Benefits Vary With Docetaxel and Abiraterone in High-Risk Prostate Cancer

Excerpt:

“The first head-to-head comparison of docetaxel and abiraterone acetate for high-risk prostate cancer patients starting long-term hormone therapy found benefit with both treatments when added to androgen deprivation therapy (ADT). Treatment decisions may come down to specific toxicities, which differ between the treatments.

“The large STAMPEDE trial previously found that both docetaxel and abiraterone improved outcomes when compared with placebo. “Right now, oncologists and urologists want to know which combination is preferable, which is why we conducted this analysis,” said study author Matthew Sydes, MSc, a statistician at University College London.”

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Abiraterone/ADT Combo Increased Prostate Cancer Survival

Excerpt:

“Combined therapy with abiraterone acetate/prednisone plus androgen deprivation therapy (ADT) significantly improved overall survival and radiographic progression-free survival (PFS) among men with metastatic hormone-naive prostate cancer compared with ADT and placebo alone, according to the results of the phase III LATITUDE trial (abstract LBA3) presented at the 2017 ASCO Annual Meeting.

” ‘In my opinion, these findings support the fact that adding abiraterone and prednisone to castration should now be considered the new standard of care for men with newly diagnosed metastatic prostate cancer,’ said researcher Karim Fizazi, MD, PhD, head of the department of cancer medicine at Gustave Roussy, University Paris-Sud, Villejuif, France.”

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Cabazitaxel/Abiraterone Combination Promising in mCRPC

Excerpt:

“The combination of cabazitaxel and abiraterone was well tolerated and showed antitumor activity in previously treated patients with metastatic castration-resistant prostate cancer (mCRPC), according to a new phase I/II study.

” ‘Therapeutic options for men with mCRPC have evolved considerably with the approval of five therapies associated with improved overall survival,’ wrote study authors led by Christophe Massard, MD, PhD, of Gustave Roussy Cancer Campus in Villejuif, France. Still, ‘there is a need to provide robust evidence on how these agents should be used, in sequence or in combination, to achieve optimal medical management.’ ”

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ASCO: Combo Tx Fails in Local High-Risk Prostate Ca

Excerpt:

“Neoadjuvant enzalutamide (ENZA) and abiraterone acetate (AA) plus 5 mg prednisone daily can be given safely for 6 months in men with localized high-risk prostate cancer prior to prostatectomy, a neoadjuvant study showed.

“However, the findings did not favor adding ENZA to augment AA plus leuprolide acetate (LHRHa) efficacy in localized high-risk prostate cancer, Eleni Efstathiou, MD, PhD, of the University of Texas MD Anderson Cancer Center, in Houston, said during a presentation at the American Society of Clinical Oncology.

“Pathologic downstaging (≤ pT2N0) occurred in 30% of patients treated with the combination therapy (AA+ENZA+ LHRHa) versus 52% of patients who received AA plus LHRHa alone (P=0.07), the study showed. Despite universal PSA depletion (≤ 0.1), a wide range of viable tumor was observed (volume 0-8.64 cc, cellularity 0-90%, and a tumor epithelial volume [TEV] 0-5.58 cc). TEV and stage were aligned.”

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Presence of AR-V7 in Circulating Tumor Cells Validated as Predictive Biomarker for Advanced Prostate Cancer Treatment by Memorial Sloan Kettering and Epic Sciences

Excerpt:

“Detecting AR-V7 positive tumor cells circulating in the blood of an advanced prostate cancer patient predicts that he will not only fail the commonly-prescribed androgen receptor signaling inhibitors (ARSI), abiraterone and enzalutamide, but that he will survive significantly longer if treated with a taxane based chemotherapy regimen.

“This discovery, published today in JAMA Oncology, emerged from a study of 161 progressing metastatic castration-resistant prostate cancer (mCRPC) patients about to start an FDA approved ARSIs or taxane as a first, second or third line treatment at Memorial Sloan Kettering Cancer Center (MSK). Blood samples taken along with those routinely collected from the patients were analyzed on the Epic Sciences’ liquid biopsy platform for circulating tumor cells (CTCs) with the AR-V7 biomarker. Overall, almost 20% of patients had AR-V7 positive CTCs.

” ‘The percentage of men that responds to ARSIs is highest in the first line setting, decreasing steadily as more treatments are given. We found that a novel liquid biopsy for AR-V7 was able to identify, with specificity, patients who will not benefit from these therapies and should instead start chemotherapy independent of the line of therapy being administered,’ said Howard Scher, M.D., chief of the genitourinary oncology services at MSK and corresponding author for the study.”

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Steroid Use With Abiraterone Offers Multidimensional Benefits to Patients With mCRPC

Excerpt:

“For decades, the standard of care for men with advanced prostate cancer has been the depletion or inhibition of androgens. While androgen-deprivation therapy (ADT) often results in temporary tumor regression or symptom relief in some patients, disease progression ultimately occurs over time. For patients with metastatic disease, the median overall survival (OS), until very recently, had been less than 2 years after chemotherapy.

“While tumor progression with ADT was previously believed to be hormone-refractory or androgen-independent, a large body of evidence supports that metastatic castration-resistant prostate cancer (mCRPC) is commonly driven by elevated steroid synthesis, increased expression or splice variants of the androgen receptor (AR), or AR ligand promiscuity, indicating the ongoing need for targeted androgen therapies.”

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Video: Dr. Antonarakis on Galeterone for Prostate Cancer

“Emmanuel Antonarakis, MBBCh, associate professor of Oncology, associate professor of Urology at Johns Hopkins Medicine, discusses the use of galeterone in prostate cancer.

“Galeterone is an oral androgen receptor inhibitor which also inhibits the ip17 enzyme, similarly to abiraterone.

“It can also degrade the androgen receptor protein and ARV7. Because of this, galeterone may demonstrate some activity in patients who have tumors that express ARV7.”

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Blood Test Picks out Prostate Cancer Drug Resistance

“Scientists have developed a blood test that can identify key mutations driving resistance to a widely used prostate cancer drug, and identify in advance patients who will not respond to treatment.

“The new research paves the way for information from a  to inform  in future, with only those  whose cancers are free of resistance mutations taking the drug, abiraterone.

“The study is also a proof of principle that tests for cancer DNA in the bloodstream can be used to detect  – allowing patients who will not benefit from one drug to be given an alternative treatment instead.

“Researchers at The Institute of Cancer Research, London, the Royal Marsden NHS Foundation Trust, and the University of Trento, Italy, analysed 274 blood samples from 97 patients using state-of-the-art DNA sequencing techniques.

“They found that mutations in a gene called the androgen receptor (AR) predicted resistance to the prostate cancer drug abiraterone, and that patients with these mutations had poorer survival.”