Selinexor (KPT-330) May Be Safe in Patients With Advanced Solid Tumors
Selinexor (KPT-330) may be a safe therapeutic option with broad antitumor activity in patients with advanced solid tumors.
Selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), may be a safe therapeutic option with broad antitumor activity in patients with advanced solid tumors, according to a study published in the Journal of Clinical Oncology.1
Researchers led by Albiruni Abdul Razak, MD, of the Princess Margaret Cancer Centre in Toronto, Ontario, looked at 189 patients with advanced solid tumors who had received KPT-330 in 21- or 28-day cycles.
They determined pre- and post-treatment levels of XPO1 mRNA in patient-derived leukocytes through reverse transcriptase quantitative polymerase chain reaction, and examined tumor biopsies through immunohistochemistry for any changes in markers consistent with XPO1 inhibition. Antitumor response was assessed through Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
The study found that the most common treatment-related adverse events were fatigue (70%), nausea (70%), anorexia (66%), and vomiting (49%), which were generally grade 1 or 2. The most commonly reported grade 3 or 4 toxicities were thrombocytopenia (16%), fatigue (15%), and hyponatremia (13%).
Maximum tolerated dose was defined as 65 mg/m2 using a twice-a-week dosing schedule. The recommended phase 2 dose of 35 mg/m2 administered twice a week was chosen based on better patient tolerability and no demonstrable improvement in radiologic response or disease stabilization compared to higher doses.
Dose-dependent elevations in XPO1 mRNA in leukocytes were demonstrated up to a dose level of 28 mg/m2 before plateauing, and paired tumor biopsies showed a nuclear accumulation of key tumor-suppressor proteins, reduction of cell proliferation, and induction of apoptosis.
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In total, among 157 patients who were evaluable for response, 1 had a complete response and 6 had partial responses, with 27 patients achieving stable disease after at least 4 months.
“Selinexor is a novel and safe therapeutic with broad antitumor activity,” the authors concluded.
- Abdul Razak AR, Mau-Soerensen M, Gabrail NY, et al. First-in-class, first-in-human phase I study of selinexor, a selective inhibitor of nuclear export, in patients with advanced solid tumors [published online ahead of print February 29, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.3949.