Progestin shows therapeutic potential in PR-positive endometrial cancer

Progestin therapy appears to yield high response rates in advanced stage and recurrent endometrial cancer (EC) that is positive for progesterone receptor (PR) expression, while having low toxicity, according to a study.

Researchers conducted a systematic review and meta-analysis to evaluate the response to and toxicity of progestin therapy and stratify response according to PR expression and tumour grade. They searched multiple online databases for studies that involved patients with advanced stage or recurrent EC treated with progestin monotherapy.

The search yielded 26 studies (four randomized controlled trials, 10 prospective studies, and 12 retrospective studies) for inclusion in the meta-analysis. The pooled study population comprised 1,639 patients, with a mean age that ranged 60–79 years. The studies examined different types and dosages of progestins, with 13 studies evaluating treatment with either megestrol acetate or medroxyprogesterone acetate. None of the studies explored adjuvant therapy, had fewer than 10 samples, and included patients with sarcoma histology.

Based on the quality assessment, a moderate risk of bias was detected for 17 studies (65.3 percent) and a high risk of bias for nine studies (34.7 percent).

Pooled data showed that progestin therapy was associated with an objective response rate of 30 percent (95 percent confidence interval [CI], 25–36) and clinical benefit rate of 52 percent (95 percent CI, 42–61). Of note, response was higher among patients with PR-positive vs -negative disease (55 percent vs 12 percent; risk difference, 43 percent, 95 percent CI, 15–71).

Adverse effects to progestin treatment were mostly mild, occurring in 28.8 percent of patients, and these effects were mainly mild. Severe toxicity was documented in 6.5 percent of patients, with the highest toxicities reported for megestrol acetate at a dose of 800 mg/day. Thromboembolic processes were the most common severe adverse effect.