Digging in to questions that matter for men with prostate cancer

Cancer researchers presented more than 5,200 study findings at the American Society of Clinical Oncology meeting in June. Amid the hubbub, Knight Cancer Institute Deputy Director Tom Beer, M.D., observed, “All of the progress that we see here at ASCO is largely the result of patients who are courageous enough to volunteer for clinical studies.”

With three expert colleagues at the meeting in Chicago, Beer led an online discussion digging in to questions that matter for men with prostate cancer: how shorter courses of radiation therapy can maintain effectiveness but reduce the burden on men with localized prostate cancer; how chemotherapy improves long-term quality of life and life expectancy in patients with advanced disease; how inherited genes may be driving a much larger share of aggressive prostate cancers than anyone assumed.

“There are many good ideas in oncology and those of us that have been in the field for some time have seen many great ideas fail. Some ideas that we thought were mediocre succeed wildly.”

In one of the biggest surprises of the meeting, researchers reported that more than 11 percent of men with advanced, metastatic prostate cancer carry inherited mutations that are associated with a defect in the DNA repair pathways.

“The most famous of these are so-called BRCA genes, BRCA1 and BRCA2,” Beer said. “Eleven percent. That’s a surprise. Should we be offering testing for these inherited defects for our patient with advanced prostate cancer? And what are the implications for their families?”

DNA repair mutations generally promote cancerous growth and resistance to treatment. But at ASCO, researchers described how certain DNA repair defects might make prostate cancer vulnerable to the new class of drugs called PARP inhibitors.

“It offers the potential hope that if we detect these mutations we might be able to target that biology,” said Russell Szmulewitz, M.D., an assistant professor of medicine at the University of Chicago.

In another study, researchers showed that an altered version of the androgen receptor gene, known as AR-V7, may predict resistance to the hormone therapies enzulutimide and abiratirone.  About one-third of patients with castrate resistant prostate cancer have circulating tumor cells with the AR-V7 variant.

“Within the next six months I think that there will be some commercially available biomarkers to test for this abnormality,” Johns Hopkins School of Medicine Assistant Professor Emmanuel Antonarakis, M.D., told Beer.

Negative results in another study should serve as a caution to cancer physicians, Beer said. Researchers reasoned that adding enzalutamide to aberaterone and standard hormonal therapy would boost the effectiveness, but it did not.

“To me it is a reminder that we need to stay humble and do the studies,” Beer said. “There are many good ideas in oncology and those of us that have been in the field for some time have seen many great ideas fail. Some ideas that we thought were mediocre succeed wildly. Evidence really is king. Until we know, we ought to stay humble and make sure that we recognize that things don’t always turn out the way we think they might.”

Watch the full conversation online at the Patient Power website.

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Inherited mutations in DNA repair genes in men with metastatic castration-resistant prostate cancer by Peter Nelson and others, J Clin Oncol 34, 2016 (suppl; abstr 5009)

Co-targeting androgen receptor (AR) and DNA repair: A randomized ETS gene fusion-stratified trial of abiraterone + prednisone (Abi) +/- the PARP1 inhibitor veliparib for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) (NCI9012)—A University of Chicago phase II consortium trial by Maha Hussain and others, J Clin Oncol 34, 2016 (suppl; abstr 5010)

AR-V7 and CTC heterogeneity biomarkers additively to predict patient (pt) outcomes with taxanes relative to approved AR targeted therapy by Howard I. Scher and others, J Clin Oncol 34, 2016 (suppl; abstr 5013)