ASCO Issues New Metastatic Prostate Cancer Treatment Guide

Liam Davenport

April 18, 2018

Men with metastatic noncastrate prostrate cancer (NCPC) experience a survival benefit with the addition of docetaxel (Taxotere, Pfizer) chemotherapy or abiraterone acetate (Zytiga, Janssen) to androgen deprivation therapy (ADT), conclude clinical practice guidelines that described both options as a standard of care.

Examining evidence from recently published phase 3 randomized controlled trials (RCTs), an expert panel convened by the American Society of Clinical Oncology found that both drugs offered significant survival advantages when offered in combination with ADT for metastatic NCPC.

However, the guideline, which was published online in the Journal of Clinical Oncology on April 2, cautioned that the two drugs have not been compared directly, and so it is not known whether some men would benefit more from one vs the other.

Lead author, Michael J. Morris, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News that for clinicians choosing between docetaxel and abiraterone, the considerations range "from the practical to the very cerebral."

He said that "on the practical side, six doses of chemotherapy takes about 18 weeks to achieve." On the other hand, abiraterone is taken continuously.

Patients who want to finish their treatment quickly may prefer docetaxel, said Morris.

The second consideration is financial, "depending on the healthcare system in which you are receiving your care."

He explained: "For patients who don't have drug coverage, the chemotherapy option could be quite a bit cheaper than the abiraterone option."

As reported by Medscape Medical News, 10 cycles of generic docetaxel plus ancillary cost $14,839, whereas 6 months of abiraterone plus prednisolone costs $30,000.

Morris continued: "From a scientific standpoint, we don't actually know which is better, but there are some patients who have disease which may not be entirely driven by the androgen receptor; that is, patients may have quite a bit of metastatic disease, in which case chemotherapy might be the more biologically appropriate option."

He added: "We don't know that for certain, but for patients who either have very high-grade disease, are poor prostate-specific antigen producers, have a neuroendocrine component or a small cell component, they may do better with chemotherapy than with abiraterone."

On the other side of the coin, Morris said that the "major force that is in favor of abiraterone is that it's really well tolerated. It's easy to take."

"You just take four tablets a day and its side effect profile is really, for many, more favorable than chemotherapy."

He summarized: "There are practical concerns, quality-of-life concerns, financial concerns, and biological concerns why a doctor and a patient might put their heads together and decide on one option vs another."

To determine whether there is an overall survival (OS) advantage with the addition docetaxel or abiraterone to ADT in men with metastatic NCPC, a multidisciplinary expert panel, including a patient representative, was convened.

They conducted a systematic review of the available evidence, restricting the search to phase 3 RCTs published in English between 2015 and 2017.

From this, they identified four relevant trials: GETUG-15, CHAARTED (ECOG 3805), STAMPEDE, and LATITUDE.

GETUG-15, STAMPEDE, and CHAARTED looked at OS with adding docetaxel to ADT.

STAMPEDE and CHAARTED indicated that, in comparison with ADT alone, docetaxel was associated with a significant survival benefit, at hazard ratios of 0.78 (n = 2962) and 0.73 (n = 790), respectively. In contrast, GETUG-15 was negative.

LATITUDE and STAMPEDE assessed the addition of abiraterone to ADT, with both studies finding a survival advantage vs ADT alone, at hazard ratios of 0.62 (n = 1198) and 0.63 (n = 1917), respectively.

The panel therefore recommended that both treatment options represent separate standards of care for metastatic NCPC, underlining that their use "in combination or in series has not been assessed and therefore cannot be recommended."

They say that docetaxel plus ADT "should be offered" to men with metastatic NCPC who have high-volume disease and are candidates for chemotherapy, while it "may be offered" to men with low-volume disease who are chemotherapy candidates.

They note that while the strongest evidence of a benefit with docetaxel is in men with de novo metastatic or high-volume disease, other patients may be offered the drug, although the evidence is "less compelling."

The panel adds: "The criteria are agnostic to the presence or absence of nodal disease."

The combination of abiraterone and ADT "should be offered" to men with high-risk de novo metastatic NCPC, the panel says, and "may be offered" to men with lower-risk de novo disease.

High-risk factors associated with a poor prognosis among men treated with abiraterone identified in LATITUDE include a Gleason score of 8 or greater, at least three bone lesions, and measurable visceral disease.

For choosing between the two drugs, the panel writes: "In the absence of randomized data comparing the addition of docetaxel versus abiraterone to ADT in men with metastatic non-castrate disease, additional variables including patient comorbidities, toxicity, QOL [quality of life] considerations, drug availability, and cost will ultimately be taken into consideration."

All funding for the administration of the project was provided by ASCO. Morris reports consulting or advisory roles with Astellas Pharma, Bayer HealthCare Pharmaceuticals, Endocyte, and Advanced Accelerator Applications; research funding from Bayer HealthCare Pharmaceuticals (institutional), Sanofi (institutional), Endocyte (institutional), and Progenics (institutional); and travel/accommodations/expenses from Bayer HealthCare Pharmaceuticals and Endocyte. Other authors declare numerous other potential conflicts of interest.

J Clin Oncol. Published online April 2, 2018. Abstract

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