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Abstract
Background Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41).
Primary Objective To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.
Study Hypothesis Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo.
Trial Design This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.
Major Inclusion/Exclusion Criteria Eligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse.
Primary Endpoint The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population.
Sample Size A total of 220 patients will be enrolled.
Estimated Dates for Completing Accrual and Presenting Results Accrual is expected to be completed in 2024 with presentation of results in 2025.
Trial Registration NCT05611931
- Uterine Cancer
Data availability statement
There are no data in this work.
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Introduction
Endometrial cancer is the sixth most commonly diagnosed cancer in women globally with alarming increases in incidence across all age groups in middle- to high-income countries.1 For patients with advanced/recurrent endometrial cancer, current treatment options include surgery, systemic, hormonal, or targeted therapies, as well as radiation, with a combination of the chemotherapy drugs carboplatin and paclitaxel as standard front-line treatment.
Molecular characterization has become an instrumental part of informed treatment decisions in patients with endometrial cancer given their prognostic and, in some cases, predictive, value.1 In combination with histopathological classification, biomarker-driven treatments can lead to improved patient management and clinical outcomes. Access to full molecular profiling is uncommon and the use in routine clinics is scant. While The Cancer Genome Atlas (TCGA) classifications were developed from a genome-wide analysis,2 the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) was derived from data integrating features of molecular and histological subtypes. The following four risk categories have emerged from ProMisE: (1) polymerase epsilon exonuclease domain mutated (POLE EDM); (2) mismatch repair deficient (dMMR); (3) tumor protein 53 abnormal (TP53abn), and (4) TP53 wild type (wt).3 According to the TCGA molecular categories, TP53wt endometrial cancer is often also characterized as NSMP (no specific molecular profile), encompassing endometrial cancer that does not exhibit features of the POLE, dMMR, or TP53abn molecular subgroups and therefore does not have a surrogate marker. This combination of assessments by immunohistochemical expression for mismatch repair proteins together with sequencing for POLE mutations allows subgroups to be defined in order to allocate risk, inform prognosis, and potentially identify novel treatment strategies.
Tumor protein 53 (TP53) is a well-recognized, prognostic, genetic biomarker for endometrial cancer, with tumors with mutations in TP53 resulting in poor outcomes.1 Approximately 25% of patients with endometrial cancer have mutations in TP53 at diagnosis and approximately 50% of advanced/recurrent endometrial cancer tumors are TP53wt, of which 40–55% are also mismatch repair proficient (pMMR) or microsatellite stable (MSS).4–6 POLE, TP53wt, and pMMR subgroups are found in approximately 36% of advanced or recurrent endometrial cancer.7 Patients with TP53wt tumors have a paucity of options and limited evidence of beneficial treatment that leaves a notable unmet need. In addition, patients with advanced/recurrent endometrial cancer who need second-line treatment commonly develop chemoresistance, have poor response to treatment, and experience substantial toxicity.8
Selinexor is an investigational oral exportin 1 (XPO1) inhibitor that prevents the XPO1-mediated export of several tumor suppressor proteins (TSPs), including wt p53 (Figure 1). Aberrant XPO1-mediated nuclear export of p53 is a mechanism by which cancer cells can inhibit regulatory and functional activities of TP53, which is a tumor suppressor gene. Overexpression of XPO1 is associated with a poor endometrial cancer prognosis and 57% of endometrial cancer tumors have a high expression of XPO1.9 Selinexor is currently approved for use in relapsed/refractory multiple myeloma and has received accelerated approval for relapsed/refractory diffuse large B cell lymphoma.10 Inhibition of XPO1 leads to nuclear accumulation of p53 across various cancer types, including endometrial cancer, as observed in cell lines and patient samples.9 While there are several mechanisms by which selinexor induces cancer cell death, the primary mechanism in endometrial cancer is presumed to be through the nuclear retention and reactivation of TP53. Promising single-agent activity of selinexor was observed in gynecological malignancies, including endometrial cancer, in the phase II SIGN study.11 In the primary analysis of the ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance therapy after first-line chemotherapy for advanced/recurrent endometrial cancer, the improvements in median progression-free survival for the intent-to-treat population were not clinically meaningful.5 In the long-term follow-up of the pre-specified TP53wt subgroup as of September 1, 2023, there were progression-free survival improvements in patients receiving selinexor maintenance therapy (80 mg oral once-weekly) compared with placebo (27.4 months vs 5.2 months, HR=0.41; median follow-up of 28.9 months). Further analysis suggests benefit is regardless of microsatellite stability status.12 An increase in progression-free survival was observed particularly in the TP53wt/pMMR (MSS) subgroup with selinexor maintenance therapy (not reached) compared with 4.9 months with placebo, HR: 0.32, median follow-up of 31.6 months). The TP53wt/dMMR (MSI-H) subgroup reached a median progression-free survival of 13.1 months with selinexor versus 3.7 months with placebo (HR=0.45).12 The safety profile for selinexor in the TP53wt subgroup was generally manageable with nausea, vomiting, and diarrhea as the most common adverse events.12 The complete safety profile of the ENGOT-EN5/GOG-3055/SIENDO study where patients received 80 mg selinexor dose has been published.5 The ENGOT-EN5/GOG-3055/SIENDO study showed that TP53wt and TP53wt/pMMR status may represent a robust predictive biomarker for selinexor efficacy in endometrial cancer, in addition to its role as an important prognostic marker.12 Based on the efficacy and safety of selinexor monotherapy from existing data, the ENGOT-EN20/GOG-3083/XPORT-EC-042 study will evaluate the safety and efficacy of once-weekly selinexor (60 mg) versus placebo to prolong progression-free survival in patients with TP53wt endometrial cancer, especially in patients with TP53wt/pMMR (MSS) tumors.5
Selinexor mechanism of action. Selinexor is an oral exportin 1 (XPO1) inhibitor. XPO1 inhibition by selinexor results in the retention/reactivation of tumor suppressor proteins such as p53. The retention of wild type p53 and other tumor suppressor protein leads to the selective killing of cancer cells while largely sparing normal cells. Export of mRNA is prevented, which inhibits oncoprotein translation. Inhibition of mRNA export of select oncogenes decreases subsequent translation and synthesis of oncoproteins, while simultaneously targeting several oncogenic pathways involved in cancer development, maintenance, and progression.
Methods
Trial Design
ENGOT-EN20/GOG-3083/XPORT-EC-042 (NCT05611931) is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with TP53wt advanced or recurrent endometrial cancer, who have achieved a partial response or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after completing at least 12 weeks of platinum-based therapy (Figure 2). For this study, the primary objective is to evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.
Trial design. BICR, blinded independent central review; CR, complete response; EC, endometrial cancer; EQ-5D-5L, Quality of Life Questionnaire EuroQol-5 Dimensions-5 Levels; NGS, next-generation sequencing; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PFS2, progression-free survival after consecutive treatment; PK, pharmacokinetics; P.O., per oral; PR, partial response; R, randomized; RECIST, Response Evaluation Criteria in Solid Tumors; TFST, time to tirst subsequent therapy; TSST, time to second subsequent therapy; QoL, quality of life; QW, once-weekly.14
A total of 220 patients will be enrolled globally across approximately 140 sites in the United States, Europe, Israel, Australia, and Canada. Eligible patients will be randomized 1:1 to maintenance therapy with either 60 mg oral once-weekly selinexor or placebo administered in 28-day cycles on Days 1, 8, 15, and 22. Exposure/response modeling from the ENGOT-EN5/GOG-3055/SIENDO study observed pharmacokinetic analyses predicts that a 60 mg dose would provide a manageable safety profile while maintaining efficacy. The following stratification factors will be applied: primary Stage IV versus recurrent disease at the time of platinum-based therapy, along with disease status after chemotherapy (partial response vs complete response). Treatment will be continued until documented disease progression per RECIST v1.1, unacceptable adverse events, withdrawal of consent, or other reasons requiring treatment discontinuation. A blinded independent central review will be formed to review disease assessment data and independently assess disease response and time of progressive disease.
Participants
Select eligibility criteria are the following: patients 18 years of age or older, histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completion of at least 12 weeks of platinum-based therapy with or without immunotherapy, and confirmed partial response or complete response at primary Stage IV disease or at first relapse. Patients cannot have uterine sarcomas, previous treatment with an XPO1 inhibitor, and cannot have received concurrent systemic anti-cancer therapy including investigational agents ≤3 weeks prior to Cycle 1 Day 1. Table 1 contains a complete list of inclusion and exclusion criteria.
Patient eligibility criteria
Primary Endpoints
The primary endpoint is investigator-assessed progression-free survival per RECIST v1.1 in the intent-to-treat population. The key secondary endpoint is overall survival. Other secondary endpoints include safety and tolerability, time to first subsequent therapy, time to second subsequent therapy, time from randomization until the second progression event, progression-free survival assessed by blinded independent central review, and health-related quality-of-life (HR-QoL) outcomes. Exploratory endpoints include progression-free survival per histology and molecular features, complete response rate for patients who entered as partial response, duration of complete response, tumor biomarkers, and pharmacokinetics.
During pre-screening, patients will be required to provide tumor biopsies (fresh or archival) for mandatory central molecular characterization/next-generation sequencing validated testing. If all other eligibilities are met, patients known to have TP53wt endometrial cancer will be enrolled. Tumor response will be evaluated according to RECIST v1.1 by the investigator and independently by a blinded independent central review.
Adverse events will be graded by the Investigator according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grading Scale v.5.0. This includes clinically significant findings in vital signs, physical examinations, laboratory, and investigation results, including hematology and serum biochemistry.
HR-QoL outcomes will be measured by the Quality-of-Life Questionnaire EuroQol-5 Dimensions-5 Levels (EQ-5D-5L).
Sample Size
To observe up to 120 progression-free survival events (ie, progression or death due to any cause), a total of up to 220 patients will be enrolled and randomized, which provides 90% power to detect a hazard ratio (HR) with a two-sided alpha of 0.05. To compare progression-free survival of selinexor versus placebo, a two-sided stratified log-rank test adjusting for stratification factors will be performed (primary Stage IV vs recurrent disease at the time of platinum-based therapy and disease status after chemotherapy (partial response vs complete response). When approximately 36 progression-free survival events are reached throughout both treatment arms, an interim analysis (futility of progression-free survival) will be performed.
Randomization and Blinding
Randomization will occur in a double-blind fashion in a 1:1 ratio of 60 mg selinexor or placebo maintenance therapy. Patients will be stratified according to the following two factors: (1) primary Stage IV versus recurrent disease at the time of platinum-based therapy and (2) disease status after chemotherapy (partial response vs complete response). Patient treatment assignments will be blinded to all staff including blinded administration during blinded study period.
Statistical Analysis
The primary endpoint of progression-free survival is defined as the time from randomization until progressive disease or death due to any cause or whichever occurs first. To compare progression-free survival and secondary time to event endpoints between treatment groups, a two-sided stratified log-rank test adjusted for stratification factors will be used. A stratified Cox proportional hazards model will be used to estimate the hazard ratio and corresponding two-sided 95% confidence intervals. The Kaplan–Meier method will be used to plot the progression-free survival and secondary time to event endpoints by treatment group. Raw scores for HR-QoL measures for both multi- and single-item measures will be linearly transformed to a score ranging from 0 to 100.
Discussion
Standard treatments for patients with advanced or recurrent endometrial cancer have limited disease control especially in those who relapse after first-line therapy.1 8 Maintenance therapy following first-line systemic chemotherapy could potentially prolong intervals between treatments with fewer disease symptoms and treatment-related toxicities, therefore providing the added benefit of improved quality of life. The lack of effective treatment has resulted in an interest in using molecular classification as not only a prognostic marker in endometrial cancer, but also as a means to direct therapy, placing an emphasis on biomarker-driven targeted therapy to maximize therapeutic strategies.1 For endometrial cancer, this could lead to an individualized treatment approach using selinexor specifically for tumors that are TP53wt and TP53wt/pMMR (MSS).
The overall frequency of TP53wt tumors in endometrial cancer and lack of specific therapy highlights this unmet need. While immune checkpoint inhibitors such as dostarlimab have shown significant benefit compared with placebo in patients with dMMR (MSI-H) endometrial cancer, less evidence of benefit was seen in patients with pMMR (MSS) endometrial cancer.13 Relatedly, in February 2023, the US Food and Drug Administration (FDA) approved dostarlimab concomitantly with chemotherapy and as maintenance therapy for patients with dMMR advanced or recurrent endometrial cancer. This emphasizes the further need to consider molecular profiles to develop agents for tumors with classifications such as TP53wt/pMMR (MSS). The ENGOT-EN5/GOG-3055/SIENDO study suggests that selinexor maintenance therapy may provide survival benefit in TP53wt endometrial cancer tumors, including those that are TP53wt/pMMR. Building on these data, the ENGOT-EN20/GOG-3083/XPORT-EC-042 will further investigate the potential role for a TP53wt-directed approach in strategically selecting the most suitable maintenance therapy for patients with advanced/recurrent endometrial cancer.
This phase III trial offers a potential option for an oral-only maintenance therapy to delay the next recurrence of disease (or in rare cases to prevent recurrence), allowing patients to have a longer disease-free period thereby improving quality of life. Based on the exploratory analysis in the ENGOT-EN5/GOG-3055/SIENDO study, there appears to be benefit of selinexor treatment for patients with pMMR (MSS) and TP53wt endometrial cancer.5 The data from this trial will provide important information about the safety, efficacy, and quality of life of selinexor as a maintenance strategy for patients with TP53wt endometrial cancer that may ultimately lead to the use of TP53 as marker for clinical decision-making.
In summary, the ENGOT-EN20/GOG-3083/XPORT-EC-042 trial may influence current practice by providing clinicians with an option of a convenient and safe oral maintenance therapy for patients with advanced/recurrent TP53wt endometrial cancer. ENGOT-EN20/GOG-3083/XPORT-EC-042 is actively enrolling patients with TP53wt advanced/recurrent endometrial cancer.
Data availability statement
There are no data in this work.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and will be conducted in accordance with the ethical principles that originate from the Declaration of Helsinki and that are consistent with International Council for Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and regulatory requirements, as applicable. This study will be conducted in collaboration with the European Network of Gynaecological Oncological Trial groups (ENGOT) and the Belgium and Luxembourg Gynaecological Oncology Group (BGOG) and the Gynecologic Oncology Group-Foundation (GOG-F) according to the ENGOT-GOG model C. Participants will give informed consent to participate in the study before taking part.
Footnotes
X @DebbieRic23, @mccarthymt7, @gyncancermd, @rcoledude
Contributors IV: conceptualization, data curation, formal analysis, investigation, validation, writing - original draft, writing - review and editing, guarantor. APF: investigation, methodology, writing - review and editing. GV: investigation, methodology, writing - review and editing. BJM: investigation, methodology, writing - review and editing.TH: investigation, methodology, writing - review and editing. DC: investigation, methodology, writing - review and editing. NC: investigation, methodology, writing - review and editing. BP: investigation, methodology, writing - review and editing. JS: investigation, methodology, writing - review and editing. JK: investigation, methodology, writing - review and editing. JB: investigation, methodology, writing - review and editing. CAP: investigation, methodology, writing - review and editing.TvG: investigation, methodology, writing - review and editing. DR: investigation, methodology, writing - review and editing. MMC: investigation, methodology, writing - review and editing. YA: investigation, methodology, writing - review and editing. MRM: investigation, methodology, writing - review and editing. KL: investigation, formal analysis, methodology, writing - review and editing. PK: investigation, formal analysis, methodology, writing - review and editing. BS: investigation, methodology, writing - review and editing. RLC: investigation, methodology, writing - review and editing.
Funding This study is sponsored by Karyopharm Therapeutics, Inc. JetPub Scientific Communications LLC, funded by Karyopharm Therapeutics, Inc., assisted in the preparation of this manuscript.
Competing interests IV reports consulting for Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Regeneron, Seagen, Sotio, Verastem Oncology, Zentalis. APF has received grants/research support from AstraZeneca, Pharmamar, GSK (paid to the institution); participation in a company-sponsored speaker’s bureau for AstraZeneca, MSD, Eisai, GSK, Clovis, Pharmamar, Pharma&; and honoraria or consultation fees from GSK, Clovis, AstraZeneca, Pharmamar, Roche, MSD, Ability Pharma. BJM has received honorarium and consulting fees from Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna Health Care, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL, Verastem, Zentalis; and speaker/consultant fees from AstraZeneca, Clovis, Easai, Merck, Roche/Genentech, TESARO/GSK. TH reports scientific advisory board participation: Aadi, AZ, Caris, Clovis, Corcept, Epsilogen, Eisai, Genentech, GSK, J&J, Merck, Seagen. GV reports grants or contracts from advisory boards of AZ, MSD, Clovis, GSK Pharmamar, Eisai. Consulting fees, honoraria, and support for attending meetings from advisory boards of AZ, MSD, Clovis, GSK, Pharmamar, Eisai. DC has nothing to disclose. NC reports fees for advisory board membership for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Oncxerna, Pieris, Roche, Novocure; fees as an invited speaker for AstraZeneca, Clovis Oncology, GSK, MSD/Merck, Eisai; institutional research grants from AstraZeneca, Roche, GSK; non-remunerated activities as member of the ESMO Guidelines Steering Committee and chair of the Scientific Committee of ACTO (Alleanza contro il tumore Ovarico). BP reports grants, advisory board, and consultant fees; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genetech/Roche, Celsion, Karyopharm, Mersana, Takeda Pharmaceuticals, Toray, Imab, Sutro, SeaGen, Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, Lily, Mersana, Onconova, Merck, Clovis Oncology, Eisai, Toray, Sutro, Deciphera, Imab, SeaGen, GOG Foundation. JS reports research funding: Institution: AZ, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. Consulting/advisory boards: AZ, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, J&J, Roche, Ingress Health, Riemser, Sobi, GSK, Novartis; honoraria: AZ, Eisai, Clovis Oncology, Olympus Medical Systems, J&J, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, Bayer. Travel, accommodation, expenses: AZ, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus. JK has nothing to disclose. JB reports participation on advisory boards for AstraZeneca, Clovis, Mersana, OncoC4, Immingen. Speaker's bureau for AstraZeneca, Merck. CP reports honoraria from Novartis, Astra Zeneca, Genesis, MSD Oncology, Servier, WinMedica; has received fees for consulting or advisory role from Amgen, Astellas, BioPharma, Roche Hellas, Astra Zeneca; and research funding from Roche Hellas, WinMedica, Servier. TvG has received grants/research supports (all paid to institution) from Amgen, AstraZeneca, Roche; advisory board (all paid to institution): AstraZeneca, BioNTech, Eisai, GSK, ImmunoGen, Incyte, Karyopharm, MSD, OncXerna, Seagen, Tubulis, Zentalis; participation in a company sponsored speaker’s bureau (all paid to institution): GSK, ImmunoGen, MSD. DR has received fees for advisory boards from Mersana, GlaxoSmithKline, AstraZeneca, ProfoundBio, Eisai, Immunogen. Grants/research supports paid to institution from GlaxoSmithKline, Lilly, Celsion, Mersana, Hookipa, Syros, AstraZeneca, Shattuck Labs, ProfoundBio, CanariaBio, Immunogen, Karyopharm. MMC has nothing to disclose. YA has received grants/research supports from AstraZeneca; honoraria or consultation fees from AstraZeneca; MSD, Eisai, GSK. Consulting or advisory role with AstraZeneca, Eisai, MSD, GSK, Pfizer. MRM has received grants/research supports from AstraZeneca (institution); Boehringer Ingelheim (institution); Pfizer (institution); Tesaro (institution); honoraria or consultation fees from honoraria: Advaxis, AstraZeneca, Cerulean Pharma, Clovis Oncology, Novocure, Pfizer, Roche, Tesaro; consulting or advisory role: AstraZeneca, BioCad, Cerulean Pharma, Clovis Oncology, Genmab, Karyopharm Therapeutics, Novocure, Pfizer, Tesaro; stock shareholder: Karyopharm Therapeutics, SeraCare; and leadership: Karyopharm Therapeutics. KL is an employee of Karyopharm Therapeutics. PK is an employee of Karyopharm Therapeutics. BS reports consulting or advisory roles for Genentech, Eisai, AstraZeneca, Karyopharm Therapeutics, Incyte, Clovis Oncology, Myriad Genetic Laboratories Inc., GlaxoSmithKline LLC, AbbVie Inc., Seagen Inc., Novocure Inc., Novartis, Immunogen, Agenus, Merck Sharp & Dohme, GOG Foundation. RLC has received grant/research support from AstraZeneca/MedImmune (institution), Clovis Oncology (institution), Merck (institution), Roche/Genentech (an immediate family member), Immunogen (institution), Mirati Therapeutics (institution), Amgen (institution), Pfizer (institution), Lilly (institution), Regeneron (institution); honoraria or consulting fees from Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, OncoMed, Immunogen, AbbVie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, GlaxoSmithKline, Eisai, GOG Foundation, Karyopharm Therapeutics; stock shareholder from McKesson; and is employed by US Oncology. Leadership: Onxeo. Travel, accommodation, expenses: Merck, AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG Foundation, Clovis Oncology, Sotio, Vaniam Group.
Provenance and peer review Not commissioned; internally peer reviewed.