Patients with Advanced Ovarian Cancer Seen to Benefit from Oral Therapy in Phase 2 Trial

Patients with Advanced Ovarian Cancer Seen to Benefit from Oral Therapy in Phase 2 Trial

Ovarian cancer patients who are refractory to platinum-based chemotherapy may significantly benefit from the investigative treatment selinexor, according to the results of a Phase 2 clinical trial recently presented at the European Society for Medical Oncology (ESMO) 2016 Congress, held in Copenhagen.

The trial also showed promising response rates in patients with endometrial cancer who had received at least one prior line of chemotherapy, but those with cervical cancer did not benefit as much as patients in the other two groups.

Selinexor, being developed by Karyopharm Therapeutics, is a first-in-class oral inhibitor of the nuclear export protein XPO1. Some cancer cells thrive by getting rid of tumor suppressor proteins (proteins that protect the cells from turning cancerous). By preventing these proteins from leaving the nucleus, selinexor induces the death of cancer cells, while sparing healthy cells.

The randomized, open-label Phase 2 study (NCT02025985), co-led by Ignace B. Vergote, MD, PhD, head of the department of obstetrics and gynecology, and gynecologic oncology, at Catholic University of Leuven in Belgium, was designed to assess the safety and efficacy of selinexor in patients with advanced gynecologic malignancies, including ovarian, endometrial, and cervical cancers.

The study enrolled 66 ovarian cancer patients (median age 62) who were refractory to platinum-based chemotherapy, as well as 23 patients with endometrial cancer (median age 67) and 25 patients with cervical cancer (median age 53) who had received at least one prior line of chemotherapy.

Most patients had been through extensive treatment, with the median number of prior treatment regimens for ovarian, endometrial, and cervical cancers being six, two, and three, respectively.

Patients with endometrial and cervical cancer received selinexor 50 mg/m2 twice weekly in four-week cycles, while those with ovarian cancer were randomized to three distinct treatment schedules: 50 mg/m2 twice weekly, 35 mg/m2 twice weekly, or 50 mg/m2 every week.

Results revealed that the 12-week disease control rate (incidence of complete and partial response, and stable disease) was 49 percent and 45 percent in ovarian cancer and endometrial cancer patients, respectively, but only 6 percent in those with cervical cancer. Disease control rates were comparable across all ovarian cancer treatment regimens.

“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.

Similarly, overall response, progression-free survival, and overall survival rates were comparable and promising among ovarian and endometrial cancer patients, but not among patients with cervical cancer. Indeed, median overall survival was 7 months for treated patients with ovarian cancer and 8 months for treated patients with endometrial cancer, but only 5 months for those with cervical cancer.

The researchers report that 15 patients received treatment for more than six months, and four were treated for more than one year, which they believe to be an important outcome, considering that all patients were already heavily treated.

The most common adverse events of selinexor treatment was nausea, anorexia, weight loss, and fatigue; treatment-related grade 3 adverse events included fatigue, anemia, nausea, and a reduction of platelet numbers.

The researchers noted that ovarian cancer patients receiving the once-weekly 50 mg/mdosing had lower grade 3 and 4 toxicities than those with the twice-weekly dosing schedule.

Based on these results, a Phase 1 study (NCT02269293) evaluating selinexor in combination with platinum-based chemotherapies in patients with advanced ovarian and endometrial cancers is currently recruiting participants. This study, taking place at two Memorial Sloan Kettering Cancer Center sites in New York, plans to enroll about 48 people. More information, including patient eligibility criteria, is available on the study’s clinical webpage or by clicking on the trial’s identification number, above.