“Men with advanced prostate cancer who respond poorly to one taxane-based chemotherapy regimen may benefit from switching to another, a small randomized trial reported.
“Nearly half of the men who did not achieve a ≥30% decline in prostate-specific antigen (PSA) level while receiving either docetaxel or cabazitaxel achieved a ≥50% decline when they switched to the other drug, said Emmanuel Antonarakis, MBBCh, of Johns Hopkins University in Baltimore, and colleagues.”
“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.’ ”
“Adding custirsen to cabazitaxel (Jevtana) and prednisone in the second-line setting failed to improve overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) in the phase III AFFINITY trial, according to OncoGenex, the company developing the drug.
“The open-label AFFINITY trial included 634 men with mCRPC who progressed on docetaxel. Patients were randomized to cabazitaxel plus prednisone with or without weekly custirsen. Treatment was administered until progression, unacceptable toxicity, or the completion of 10 cycles. The study was conducted at 95 locations in North America, Europe, Russia, and Australia.”
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This year’s American Society of Clinical Oncology (ASCO) annual meeting was short on any truly exciting developments in prostate cancer treatment. In stark contrast to other cancers, such as lung, breast, kidney, and melanoma, there were no reports of note on targeted and immunotherapies in prostate cancer. The two presentations summarized here offered new strategies in chemotherapy. Continue reading…
“For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel. For example, docetaxel is commonly used as the ‘first-line’ therapy, while cabazitaxel is used as the ‘second-line’ therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied. This week, however, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Center may change the perspective on a role for combination chemotherapy in advanced disease.
“The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin – a type of platinum chemotherapy—in patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, 160 men have been randomized to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.
“In a new study reported by de Leeuw et al in Clinical Cancer Research, researchers found that the novel taxane cabazitaxel (Jevtana) has properties that could make it more effective than docetaxel in some patients with advanced prostate cancer. This hypothesis is currently being tested in a phase II clinical trial. Researchers have also found a genomic marker that could help physicians identify which patients might benefit most from cabazitaxel.
“ ‘It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they’re both taxanes,’ said senior author and Professor of Cancer Biology at the Sidney Kimmel Medical College at Thomas Jefferson University. ‘It shows that we may not be taking full advantage of this next-generation taxane in the clinic.’
“For years, docetaxel has been the only effective chemotherapy for men whose prostate cancer was no longer responding to hormone treatments. The next-generation drug in the taxane family, cabazitaxel, was approved by the U.S. Food and Drug Administration (FDA) in 2010, but only for patients whose prostate cancer no longer responded to hormone therapy or docetaxel treatment.
“Dr. Knudsen and colleagues explored how cabazitaxel worked and demonstrated that it might be more effective sooner in treatment. The researchers showed that cabazitaxel worked better than docetaxel in human prostate cancer cells lines that were resistant to hormone treatment, both in terms of slowing growth of cancer cells and in its ability to kill cancer cells.”
“Prostate cancer is the second leading cause of cancer for men in the United States. Only one class of chemotherapy called taxanes is effective against the disease. A study published online this week (January 17th) in Clinical Cancer Research, researchers have found that a newer member of the taxane family called cabazitaxel, an FDA approved drug, has properties that could make it more effective for some patients – a hypothesis currently being tested in clinical trials. Researchers also found a genomic marker that could help physicians identify which patients might benefit most from cabazitaxel.
” ‘It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they’re both taxanes,’ says senior author Karen Knudsen, Ph.D., Interim Director of the Sidney Kimmel Cancer Center and a professor of cancer biology at the Sidney Kimmel Medical College at Thomas Jefferson University. ‘It shows that we may not be taking full advantage of this next generation taxane in the clinic.’
“For years, docetaxel has been the only effective chemotherapy for men whose cancer was no longer responding to hormone treatments. The next generation drug in the taxane family, cabazitaxel, was approved in 2010, but only for patients whose cancer no longer responded to hormone therapy or docetaxel treatment.”
The gist: A clinical trial is currently testing a drug called custirsen in men with metastatic, castration-resistant prostate cancer (CRPC). The patients are receiving custirsen along with the chemotherapy drug cabazitaxel. The trial recently underwent a “futility analysis” to ensure it could continue as planned. Final results will be announced later this year or in 2016.
“OncoGenex Pharmaceuticals, Inc. (OGXI) today announced that the AFFINITY trial is continuing as planned based upon completion of the interim futility analysis and the recommendation of the Independent Data Monitoring Committee (IDMC).
“The Phase 3 AFFINITY trial is designed to evaluate a survival benefit for custirsen in combination with second-line cabazitaxel chemotherapy in 635 men with metastatic castrate-resistant prostate cancer (CRPC). AFFINITY is being conducted at 95 global clinical trial sites and final survival results are expected to be announced in late 2015 or early 2016.
” ‘While the results remain blinded to OncoGenex, we are very pleased that the AFFINITY trial has passed this interim futility analysis and we remain confident in the potential value of custirsen in treating cancer, particularly in patients who have advancing disease despite previous treatments,’ said Scott Cormack, President and CEO of OncoGenex.”
“Cabazitaxel failed to meet a primary endpoint of showing superior progression-free survival (PFS) and additionally showed less favourable median overall survival (OS) compared to topotecan in an international, randomised open-label phase II trial performed in patients with small-cell lung cancer (SCLC), who had progressed during or after first-line platinum-based chemotherapy. The results were presented by Dr Tracey Evans of the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, USA in a proffered papers session at the 4th European Lung Cancer Conference (26-29 March 2014, Geneva, Switzerland).”
Editor’s note: This trial found disappointing results for the drug cabazitaxel in treating small cell lung cancer (SCLC). To read about promising SCLC treatments, see this blog feature.