Novel Drug Combo Induces Encouraging Results in Patients With Heavily Pretreated Breast Cancer

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The use of Faslodex plus the investigational drug samuraciclib was considered safe in individuals with heavily pretreated hormone receptor-positive breast cancer.

Patients with hormone receptor (HR)-positive breast cancer who were previously heavily pretreated with CDK4/6 inhibitors achieved encouraging responses after receiving Faslodex (fulvestrant) plus the novel CDK7 inhibitor samuraciclib, according to recent study results.

Moreover, the data, which were presented at the 2021 San Antonio Breast Cancer Symposium, suggested that TP53 mutational status was predictive of outcomes with samuraciclib.

Historically, patients with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses following disease progression after treatment with CDK4/6 inhibitors.

“On average, we get about a two-month progression-free survival with (Faslodex) in patients who’ve become resistant to CDK4/6 inhibitors,” lead study author Dr. Charles Coombes, director of Cancer Research at Cancer Research UK Imperial Centre in London, said during a presentation of the data.

Additionally, Coombes noted that although patients tolerate hormonal therapy well, efficacy is limited after CDK4/6 inhibitor therapy.

A once-daily, oral, small molecule selective inhibitor of CDK7, samuraciclib has shown synergistic activity with hormonal therapy in HR-positive breast cancer models. In particular, the drug shows activity when combined with the estrogen modulator tamoxifen or Faslodex.

The aim of this study was to identify the appropriate dosing regimen of the samuraciclib plus Faslodex combination and to investigate signs of preliminary activity and biomarkers.

The study comprised 31 patients (median age, 60 years; range, 41 to 81). The study participants received either 240 milligrams (mg) of samuraciclib by mouth once daily plus 500 mg of Faslodex every four weeks (6 patients) or 360 mg of samuraciclib by mouth once daily plus 500 mg of Faslodex every four weeks (25 patients).

Enrolled patients must have been aged at least 18 years, had a confirmed histology of metastatic or locally advanced ER-positive and/or PGR-positive, HER2-negative breast cancer. Patients must also have received prior treatment with CDK4/6 inhibitors, at most one line of chemotherapy or at most two lines of endocrine therapy and have had no prior exposure to Faslodex.

At 24 weeks, the study authors observed a clinical benefit rate (percentage of patients who achieve a complete response, partial response or have stable disease for at least six months) in 36% of patients. The results also showed that patients without liver metastases achieved a clinical benefit rate of 55%. Coombes noted that the clinical benefit rate rose from 36% to 53% when excluding patients with a TP53 mutation.

Of the 25 evaluable patients, 72% achieved tumor shrinkage. Additionally, in 19 patients expressing the TP53 wild type and six patients expressing TP53 mutant type, the median progression-free survival (or the time during and after treatment when the patient lives without disease progression) was 32 weeks and 7.9 weeks, respectively.

After arranging patients based on some of their clinical characteristics, the investigators observed that a median progression-free survival was not yet reached in the 17 patients who had no liver metastases; in the 14 patients with liver metastases, the median progression-free survival was 11.9 weeks.

Liver metastasis is a known risk factor for poor prognosis in HR-positive breast cancer. Future studies are planned to evaluate whether the presence of liver metastases is predictive for samuraciclib-based therapy.

The most common side effects were reversible, low-grade gastrointestinal (GI) events. The most common side effects were diarrhea (90%), nausea (81%), vomiting (74%) and fatigue (36%). The most common serious or severe side effects included diarrhea (19%) and nausea (10%).

The Food and Drug Administration, according to Coombes, has granted this combination fast-track status. Drugs given fast track status are treatments that may address unmet medical needs in serious or life-threatening conditions and may be given expedited reviews.

Future clinical studies are expected to evaluate samuraciclib in combination with oral selective estrogen receptor degraders to extend the limited progression-free survival of a single–agent endocrine therapy.

This article originally appeared on OncLive as "Samuraciclib Plus Fulvestrant Improves PFS in Heavily Pretreated HR+ Breast Cancer."

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