Increasingly, standard ADT (with LHRH agonists or antagonists) is combined with other drugs to treat advanced prostate cancer. In recent years, ADT combined with second generation anti-androgens, Zytiga, or taxane chemotherapy has been shown to slow disease progression (assessed by various measures) better than ADT alone for patients with advanced disease. This has raised the question of whether those patients may benefit from treatment with ADT combined with not just one of the newer agents, but two or more.
Researchers in Pennsylvania have now done a massive review of the many clinical trials recently completed or underway that explore this topic. In their review, they ask the following question (although not in these exact words): Are there benefits to going in with all guns blazing for advanced prostate cancer patients and treating them concurrently with ADT plus two or more other agents?
There are some subtleties in the question as many studies have not run long enough to get solid data on overall survival (OS). Typically, the researchers look at short term proxies of disease progression that can be assessed over one to three years. These can be measures like changes in the number of metastases seen radiographically or the need for pain medication.
In the clinical setting, the patients of concern have often been heavily pretreated with the drugs of interest and had their quality of life already diminished by the symptoms of their disease or the side effects of those drugs. When side effects are taken into consideration, highly aggressive, multi-drug treatment clearly means more adverse and severe side effects. The review acknowledges the large side effect burden that can come from these drugs and concludes that there is no strong evidence of OS benefit in advanced patients with castrate resistant, metastatic, symptomatic disease on two or more agents. In their own words, “[N]o improvement in OS was found in the patients with [metastatic, castrate resistant disease] treated with either double or triple therapy. This raises the question if triple therapy is truly beneficial or needed.”
To read the study abstract, see: https://link.springer.com/article/10.1007%2Fs12032-021-01520-y
Reference:
Desai, M.H., Parsi, M. & Potdar, R.R. (2021). Triple-arm androgen blockade for advanced prostate cancer: a review. Med Oncol 38, 75. https://doi.org/10.1007/s12032-021-01520-y