Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies.

BACKGROUND: Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies. METHODS: In this phase 2 trial, patients received selinexor (35 or 50 mg/m2 twice-weekly [BIW] or 50 mg/m2 once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) ≥12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1-11), 2 (1-5), and 3 (1-6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m2 QW had fewer high-grade AEs with similar efficacy as BIW treatment. CONCLUSIONS: Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care.

Symposium on health economics in oncology. Freiburg, Germany, June 1995.

Dr. E. Enghofer (Wien, Austria) summarized the content of the presentations and discussions of the symposium in his concluding remarks. 1. The organizers should be congradulated on their initiative in bringing together at the symposium experts from different disciplines, i.e., medicine, ethics, health economics, jurisprudence, the pharmaceutical industry and, last but not least, cost providers. 2. Health economics as an issue in health care has been around for quite some while. One example can be found in the German Drug Guidelines dating back to 1990, where the following terms have already been defined: therapeutic benefit, medical needs, and achieving therapeutic goals. 3. Health economics serves as a "support function" in the medical decision-making process. It has as yet no decisive role in the application to license a drug nor in questions concerning a physician's liability. Health economics as a discipline, however, was a reminder of, and served as a catalytic function for: a) The differentiation between the benefit of a medical intervention and its pure effectiveness. b) The definition of medical standards as a means to compare the quality of health care between different institutions, to uncover quality deficits and to develop strategies for the optimization of medical quality (quality management). Routine deviation from these standards is unethical. The German Cancer Society has taken on the task of defining such standards in cancer care. c) The difference between rationalising and rationing health care. The spending of the current health-care budget needs to be screened for unnecessary and/or inappropriate diagnostic procedures and treatment modalities as well as for "below-standard" care. The money that can be saved here can then be shifted towards financing "state of the art" medicine or can be used in the decision to substitute certain procedures. 4. The a priori definition of the desired outcome of a medical intervention is of paramount importance for the evaluation of the actual treatment result. Economical evaluations are easier when cure rather than palliation is the aim of a particular treatment and when alternative therapies do exist such that cost comparisons are possible. In any case, therapeutic interventions need to be adapted to the desired treatment goal; only then can the question be answered whether or not the means (cost) are (is) justified. 5. Outcome studies need to take into account every relevant medical aspect (i.e. disease management studies), and they should be accompanied by evaluation studies. The latter must also include unselected patients in daily practice.(ABSTRACT TRUNCATED AT 400 WORDS)