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The addition of the CDK7 inhibitor, samuraciclib, to fulvestrant demonstrated antitumor activity with an acceptable safety profile among patients with hormone receptor (HR)-positive advanced breast cancer, according to a small cohort study presented at the 2021 San Antonio Breast Cancer Symposium (SABCS).
“For this reason, 6 weeks ago the US FDA granted the drug fast-track status,” Charles Coombes, MD, of the Imperial College in London, United Kingdom, and lead author of the study, said.
The single-arm cohort study treated 31 patients with metastatic or locally advanced estrogen receptor (ER)-positive and/or progesterone receptor (PGR)-positive, HER2-negative breast cancer with 2 different doses of samuraciclib plus the standard dose of fulvestrant. Prior CDK4/6 inhibitor, but not fulvestrant, was allowed. The aim of the study was to determine the appropriate dosing regimen for a phase 2 trial and preliminary efficacy signals.
At baseline, the median age was 60. The most common site of metastasis was visceral, followed by bone, liver, and lymph node. All patients had previously received a CDK4/6 inhibitor and 23% had received chemotherapy in the metastatic setting, 32% in the adjuvant, and 10% in the neoadjuvant settings.
Of the 25 evaluable patients, 72% experienced tumor shrinkage. Twelve percent of patients achieved a partial response, including one that lasted for approximately 1 year. The proportion of patients with stable disease was 52%.
The 24-week clinical benefit rate was 36% overall, 55% among patients with no liver metastases, and 53% among patients whose disease was TP53 wild-type.
Progression-free survival (PFS) differed according to TP53 status. Patients whose disease was wild-type for TP53 demonstrated a median PFS of 32 weeks compared with 7.9 weeks for patients with mutated TP53 (hazard ratio [HR], 0.17; 95% CI, 0.05-0.53; P =.0008). A similar difference was observed when the results were stratified by liver metastases. PFS was significantly longer for patients who had no liver metastases compared with those with metastases at 48 weeks or longer and 11.9 weeks, respectively (HR, 0.16; 95% CI, 0.05-0.59; P =.0021).
The most common grade 3 or higher adverse events were nausea, vomiting, diarrhea, and fatigue. There were 6 patients who discontinued treatment as a result of gastrointestinal events. There were no reports of neutropenia or substantial myelosuppression.
Given the frequency of nausea, ondansetron prophylaxis is now standard-of-care for patients treated with samuraciclib. “We are also developing a tablet form of the medication, which I think is going to improve matters,” Dr Coombes said.
Dr Coombes concluded that although “it is early days here, the combination appears effective, particularly in patients with wild-type TP53 status measured by ctDNA.”