乌鸦传媒

A recent with intermittent relacorilant and nab-paclitaxel in resistant/refractory ovarian cancer showed signs of improvement in progression-free survival (PFS), duration of response (DOR), and overall survival, compared with nab-paclitaxel alone.

There remains an unmet need for efficacious and well-tolerated therapies for women with platinum-resistant ovarian cancer. Currently, the standard of care is sequential single-agent chemotherapies, with poor results. Recently an antibody drug conjugate, mirvetuximab, was approved for platinum-resistant ovarian cancer that expressed folate receptor alpha by >75%.

This was the first drug approved since 2014 for platinum-resistant ovarian cancer. Unfortunately, only 35% of ovarian tumors are high expressors of FOLR1. The majority of platinum-resistant ovarian cancer still does not have a good therapeutic option.

Cortisol modulation is emerging as a promising novel treatment platform in cancer care. Cortisol has been shown to contribute to chemotherapy resistance by suppressing the apoptotic pathway that cytotoxic agents utilize.

Relacorilant is a selective glucocorticoid receptor modulator. Intermittent relacorilant when combined with nab-paclitaxel suppressed more glucocorticoid receptor target genes than nab-paclitaxel alone.

The phase II study by Colombo et al. was a three-arm randomized, open-label trial that enrolled patients with recurrent platinum-resistant/refractory ovarian, fallopian tube, or primary peritoneal cancer who had received up to four prior lines of therapy.

A total of 178 women (median age 61; 36.5% of whom were platinum refractory) were randomly assigned 1:1:1 to receive either intermittent relacorilant at 150 mg with nab-paclitaxel at 80 mg/m² (n=60), continuous relacorilant at 100 mg with nab-paclitaxel at 80 mg/m² (n=58), or nab-paclitaxel alone at 100 mg/m² (n=60).

Nab-paclitaxel was administered on days 1, 8, and 15 to participants in each arm. For patients in the intermittent arm, relacorilant was administered on the day before, the day of, and the day after each dose of nab-paclitaxel.

The median number of prior therapies was 3 (range 1-5); 99.4% of patients had prior taxane therapy, 59.0% had prior bevacizumab, and 36.5% had prior PARP-inhibition therapy. A total of 12.1% had a BRCA1 mutation, and 6.1% had a BRCA2 mutation.

The primary endpoint was PFS, by investigator assessment per RECIST 1.1 criteria. Secondary endpoint was objective response rate, DOR, overall survival (OS), and safety.

The results showed an improved PFS, DOR, and OS with intermittent relacorilant + nab-paclitaxel compared with nab-paclitaxel alone.

These are very exciting results, opening up a new option for patients with refractory/resistant disease. A study showing improvement in OS is always welcomed, especially in a heavily treated population.

Nab-paclitaxel has been around for a while and clinicians are familiar with this drug. The study did not show any new concerning adverse effects. There is a phase III study currently ongoing and we will look forward to the results.

This combination will be a game changer for this population of ovarian cancer patients.

Veena John, MD, is system head in Gynecologic Medical Oncology at Northwell Cancer Institute and Associate Professor at Zucker School of Medicine at Hofstra/Northwell Zuckerberg Cancer Center in Lake Success, New York.

Read the study here and an interview about it here.