COMMENTARY

Prostate Cancer Preview: ASCO 2017 Data Likely to Change Practice

David L. Graham, MD

Disclosures

May 26, 2017

Those of us who have been doing this long enough remember a great many years where the ASCO Annual Meeting prostate sections were far from exciting. Thankfully, that has changed for the better. The past 5 years have seen a plethora of new drugs showing significant activity against this disease, and the past 2 years have demonstrated the benefit of considering a more aggressive line of therapy upfront in men with metastatic disease. This year we will learn the results of interesting trials looking at an alternative option for upfront treatment in men with metastatic disease, the length of androgen deprivation when used in conjunction with radiotherapy, and a potential new marker of disease response.

In the past 2 years, we have seen the results of two trials, CHAARTED and STAMPEDE, which have shown the benefit of adding docetaxel to androgen deprivation in frontline therapy for men with metastatic disease. Docetaxel can have a number of toxicities associated with its use, and there remains some hesitation in adopting its wider use in the frontline setting. Two abstracts will be presented this year—LBA3[1] and LBA5003[2]—looking at the addition of abiraterone to androgen deprivation in this same population.

LBA3 presents the results of the LATITUDE trial, a double-blind phase 3 trial of the addition of abiraterone to androgen deprivation in men with high-risk, hormone-naive, metastatic prostate cancer. Although the results of the trial will not be publically released until June 3, it should be telling that the scientific committee has chosen it to be one of the plenary abstracts.

Along with this is LBA5003, an additional report of the STAMPEDE trial. Much has been made of reported results showing the benefit of adding docetaxel, but STAMPEDE had multiple arms. LBA5003 reports the results of the arm in which abiraterone was added to androgen deprivation. This will be reported in an oral presentation on June 3 and the details of the results will be made available that morning. If the results of these two trials are in line with what their scheduling at ASCO would suggest, there may be a new option for men with newly diagnosed metastatic prostate cancer who would otherwise not be considered for more aggressive interventions.

For men who are diagnosed with higher-risk disease, adding an extended course of androgen deprivation to radiotherapy has been shown to be beneficial. The optimal length of this therapy is still to be determined. Abstract 5008[3] reports the results of a randomized phase 3 trial comparing 18 months of androgen deprivation with 36 months, each together with radiation, in men with high-risk disease. In this trial of 630 men, survival results were equivalent between the two groups but quality-of-life measures were significantly better in the men who received only 18 months of androgen deprivation therapy. Full results will need to be presented and reviewed, but this has the potential to change daily practices.

One of the difficulties in treating and following men with this disease is having a consistently good marker to follow. It took a good number of years before prostate-specific antigen (PSA) was accepted as an appropriate marker for clinical trials. PSA has its limitations, however, particularly in men with Gleason 9-10 disease or in those whose pathology has evolved during therapy. Abstracts 5006[4] and 5007[5] look at other potential measures of treatment effect.

In abstract 5006, Armstrong and colleagues describe the results of using a computational analytic on bone scan imaging in 730 men with metastatic disease treated in a placebo-controlled phase 3 trial. In their evaluation, this analysis was independently associated with overall survival even after adjustment for treatment, PSA, and a number of other variables.

Abstract 5007 describes the work of Heller and colleagues, who consolidated the circulating tumor cell (CTC) data obtained in five separate phase 3 trials. In their analysis, reduction of CTC from unfavorable to favorable levels (CTC conversion) or, in fact, complete elimination of CTC (CTC0) was found to have a significant discriminatory power for overall survival. Both of these trials, with conformation, raise the possibility of an endpoint that can significantly shorten the time required to have analyzable outcomes data in future trials.

While all of these reports look interesting in abstract form, full data presentation and discussion at ASCO 2017 will affect just how useful and influential they may be in the future of prostate cancer care. I will certainly be at these sessions. I also have no doubt that some other presentations will have an impact that none of us had anticipated.

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