Single-agent selinexor demonstrated antitumor activity in heavily pretreated patients with ovarian or endometrial cancers, according to phase 2 study results presented at the European Society for Medical Oncology Congress.
However, patients with cervical cancer did not demonstrate as much benefit as the other cohorts, results showed.
Selinexor (KPT-330, Karyopharm Therapeutics) is a first-in-class inhibitor of XPO1, a nuclear export protein that is expressed in aggressive ovarian cancers and is linked to poor outcomes. Further, data from The Cancer Genome Atlas indicates XPO1 is common in patients with endometrial cancer.
Ignace B. Vergote, MD, PhD, head of the department of obstetrics and gynecology and of gynecologic oncology at Catholic University of Leuven in Belgium, and colleagues evaluated the safety and efficacy of selinexor in 66 patients (median age, 62 years) with ovarian cancer, 23 patients (median age, 67 years) with endometrial cancer and 25 patients (median age 53 years) with cervical cancer. All patients with ovarian cancer were refractory to platinum chemotherapy, and all patients with endometrial and cervical cancers had received at least one prior line of chemotherapy.
The median number of prior treatment regimens were six (range, 1-11) inpatients with ovarian cancer, two (range, 1-5) in patients with endometrial cancer and three (range, 1-8) in patients with cervical cancer.
Researchers randomly assigned patients with ovarian cancer to one of three treatment schedules: 50 mg/m2 twice weekly, 35 mg/m2 twice weekly or 50 mg/m2 every week in 4-week cycles. All other patients received selinexor 50 mg/m2 twice weekly.
Disease control rate — or the incidence of complete response, partial response and stable disease at week 12 — served as the study’s primary endpoint. Secondary endpoints included overall response rate, PFS, duration of response, safety and tolerability.
The 12-week disease control rate was 49% in patients with ovarian cancer and appeared comparable across dosing schedules. Patients with endometrial cancer demonstrated a disease control rate of 45%, and patients with cervical cancer had a 6% disease control rate.
“We were quite surprised we saw the worst disease control rate in patients with cervical cancer, despite the fact that this is an HPV–induced tumor, where we expected more responses than in the two other cohorts,” Vergote said during his presentation.
The overall response rate was 14% among both patients with ovarian cancer, 15% among patients with endometrial cancer, and 4% among patients with cervical cancer.
Median PFS was 3 months among patients with ovarian and endometrial cancers, and 1 month among patients with cervical cancer. Median OS was 7 months in patients with ovarian cancer, 8 months in patients with endometrial cancer and 5 months in patients with cervical cancer.
Fifteen patients received treatment for more than 6 months, including four patients who have been treated for more than 1 year.
“The most important outcomes were the disease control rate, and that so many patients could tolerate treatment for longer periods despite having been heavily pretreated,” Vergote said.
Researchers also analyzed patients’ blood samples for circulating tumor cells (CTCs). Results showed that patients with CTCs prior to treatment tended to have shorter PFS.
Common grade 1 and grade 2 drug-related adverse events that occurred in all patients included nausea (56%), anorexia (47%), weight loss (44%) and fatigue (42%). Grade 3 drug-related events included thrombocytopenia (11%), fatigue (10%), anemia (9%) and nausea (8%).
One patient each experienced grade 4 cataract and hyponatremia.
Grade 3 to grade 4 toxicities were reduced in the once-weekly 50 mg/m2 dosing compared with twice-weekly dosing, Vergote said.
Based on these results, phase 3 trials are planned to evaluate selinexor in patients with ovarian and endometrial cancers.
“Single-agent selinexor has interesting antitumor activity in heavily pretreated ovarian and endometrial cancers,” Vergote said. “With this data, cervical cancer will not be a priority for future research, but endometrial cancer will be.”
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