Uterine Corpus Cancer

Rising colorectal cancer incidence has rapidly shifted mortality patterns in adults under 50 years of age; colorectal cancer has moved up from being the fourth leading cause of cancer death in both younger men and women two decades ago to first in men and second in women. Cancer deaths in the United States are falling, with more than 4 million fewer deaths since 1991. The mortality rate has dropped as a result of less smoking, earlier detection for some cancers and improved treatment, according to Rebecca Siegel, senior scientific director, surveillance research at the American Cancer Society and lead author of ACS's new annual report. But, this progress is jeopardized by increasing incidence for 6 of the top 10 cancers as the projected number of new diagnoses now tops 2 million for the first time, according to new data. In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States.  “As a nation, we’ve dropped the ball on cancer prevention as incidence continues to increase for many common cancers—like breast, prostate and endometrial, as well as colorectal and cervical cancers in some young adults," Siegel said. For the report, ACS researchers compiled the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). Rising colorectal cancer incidence has rapidly shifted mortality patterns in adults under 50 years of age; colorectal cancer has moved up from being the fourth leading cause of cancer death in both younger men and women two decades ago to first in men and second in women. Breast cancer leads in women under 50 with 2,251 deaths in 2021. “The continuous sharp increase in colorectal cancer in younger Americans is alarming,” said Dr. Ahmedin Jemal, senior vice president, surveillance and health equity science at the American Cancer Society and senior author of the study, in a statement. “We need to halt and reverse this trend by increasing uptake of screening, including awareness of non-invasive stool tests with follow-up care, in people 45-49 years. Up to one-third of people diagnosed before 50 have a family history or genetic predisposition and should begin screening before age 45 years. We also need to increase investment to elucidate the underlying reasons for the rising incidence to uncover additional preventive measures.” Cancer patients are getting younger, according to the new ACS data. The proportion of diagnoses in people who are middle-aged (50-64 years) increased from 25% in 1995 to 30% in 2019-2020, whereas the proportion 65 years and older decreased from 61% to 58%, despite both age groups growing in the general population (from 13% to 19% for ages 50-64 years and from 13% to 17% for ages 65 and older). In addition to changes in the population age distribution, this shift reflects steep decreases in the incidence of prostate cancer and smoking-related cancers in older adults, as well as increased cancer incidence in people born after the 1950s because of higher obesity and other yet unknown factors. Other key findings from the report include: Cervical cancer incidence rates are decreasing steeply in women in their 20s, who were first to receive the HPV vaccine, but are increased in women 30-44 years old by 1.7% per year from 2012 through 2019, highlighting the need for more emphasis on screening in young women, as well as broader uptake of the vaccine.  In 2021, HPV vaccination coverage in adolescents 13-17 years ranged from 33% in Mississippi to 79% in the District of Columbia. After decades of increase, cancer incidence in children has finally leveled off, although rates continue to increase among adolescents (ages 15-19 years), including a greater than 4% per year rise in thyroid cancer, much of which is likely overdiagnosis; the 15-year survival rate for thyroid cancer in adolescents is 99%. Mortality rates continue to increase by 2% per year for uterine corpus (endometrial) cancer, one of the few cancers with increasing mortality. Steeper increases in women of color are widening racial disparities, with the death rate now two times higher in Black women (9.1 per 100,000) than in White women (4.6 per 100,000). The report also showed progress against cancer is hampered by wide static cancer disparities. Compared to White people, mortality rates are twofold higher for prostate, stomach, and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. “This report underscores the need for public policy interventions to help reduce these cancer disparities and save more lives,” said Lisa A. Lacasse, president of ACS’s advocacy affiliate, the American Cancer Society Cancer Action Network, in a statement. “We urge lawmakers at all levels of government to advance policies that ensure more people have health insurance coverage as well as improved access to and affordability of care, such as increased funding for cancer research and screening programs. Doing so will bring us closer to our vision of ending cancer as we know it, for everyone.” All of the data in the ASC reports can be accessed from the Cancer Statistics Center. 

The annual American Cancer Society report also shows colorectal cancer is now the leading cause of cancer death in men and the second in women under 50 years old. ATLANTA, Jan. 17, 2024 /PRNewswire/ -- The American Cancer Society (ACS) today released Cancer Statistics, 2024, the organization's annual report on cancer facts and trends. The new data show overall cancer mortality has continued to decline, resulting in over 4 million fewer deaths in the United States since 1991. However, this progress is jeopardized by increasing incidence for 6 of the top 10 cancers as the projected number of new diagnoses now tops 2 million (2,001,140) for the first time. These important findings are published today in CA: A Cancer Journal for Clinicians, alongside its consumer-friendly companion, Cancer Facts & Figures 2024, available on cancer.org. Continue Reading Cancer Facts & Figures 2024 Infographic "We're encouraged by the steady drop in cancer mortality as a result of less smoking, earlier detection for some cancers, and improved treatment," said Rebecca Siegel, senior scientific director, surveillance research at the American Cancer Society and lead author of the report. "But as a nation, we've dropped the ball on cancer prevention as incidence continues to increase for many common cancers – like breast, prostate, and endometrial, as well as colorectal and cervical cancers in some young adults." For the report, ACS researchers compiled the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). Rising colorectal cancer incidence has rapidly shifted mortality patterns in adults under 50 years of age; colorectal cancer has moved up from being the fourth leading cause of cancer death in both younger men and women two decades ago to first in men and second in women. Breast cancer leads in women under 50 with 2,251 deaths in 2021. "The continuous sharp increase in colorectal cancer in younger Americans is alarming," said Dr. Ahmedin Jemal, senior vice president, surveillance and health equity science at the American Cancer Society and senior author of the study. "We need to halt and reverse this trend by increasing uptake of screening, including awareness of non-invasive stool tests with follow-up care, in people 45-49 years. Up to one-third of people diagnosed before 50 have a family history or genetic predisposition and should begin screening before age 45 years. We also need to increase investment to elucidate the underlying reasons for the rising incidence to uncover additional preventive measures." "The 2024 ACS cancer report underscores the importance of cancer prevention, and illuminates priority areas to address cancers whose incidence and/or mortality rates are inexplicably rising," said Dr. Karen E. Knudsen, chief executive officer at the American Cancer Society. "These observations highlight the critical need to invest in equitable application of proven cancer control interventions, and in discovery for new therapies -- especially for advanced-stage cancers. Both endeavors will be essential to accelerate progress against the 200 diseases we call cancer, and to save lives." Other highlights from the report include: Cervical cancer incidence rates are decreasing steeply in women in their 20s, who were first to receive the HPV vaccine, but are increased in women 30-44 years old by 1.7% per year from 2012 through 2019, highlighting the need for more emphasis on screening in young women, as well as broader uptake of the vaccine. In 2021, HPV vaccination coverage in adolescents 13-17 years ranged from 33% in Mississippi to 79% in the District of Columbia. After decades of increase, cancer incidence in children has finally leveled off, although rates continue to increase among adolescents (ages 15-19 years), including a greater than 4% per year rise in thyroid cancer, much of which is likely overdiagnosis; the 15-year survival rate for thyroid cancer in adolescents is 99%. Mortality rates continue to increase by 2% per year for uterine corpus (endometrial) cancer, one of the few cancers with increasing mortality. Steeper increases in women of color are widening racial disparities, with the death rate now two times higher in Black women (9.1 per 100,000) than in White women (4.6 per 100,000). Cancer patients are getting younger: the proportion of diagnoses in people who are middle-aged (50-64 years) increased from 25% in 1995 to 30% in 2019-2020, whereas the proportion 65 years and older decreased from 61% to 58%, despite both age groups growing in the general population (from 13% to 19% for ages 50-64 years and from 13% to 17% for ages 65 and older). In addition to changes in the population age distribution, this shift reflects steep decreases in incidence of prostate cancer and smoking-related cancers in older adults, as well as increased cancer incidence in people born after the 1950s because of higher obesity and other yet unknown factors. "People younger than 65 are less likely to have health insurance and more likely to be juggling family and careers," explained Dr. William Dahut, chief scientific officer at the American Cancer Society. "Also, men and women diagnosed younger have a longer life expectancy in which to suffer treatment-related side effects, such as second cancers." The report also showed progress against cancer is hampered by wide static cancer disparities. Compared to White people, mortality rates are two‐fold higher for prostate, stomach, and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. "This report underscores the need for public policy interventions to help reduce these cancer disparities and save more lives," said Lisa A. Lacasse, president of ACS's advocacy affiliate, the American Cancer Society Cancer Action Network. "We urge lawmakers at all levels of government to advance policies that ensure more people have health insurance coverage as well as improved access to and affordability of care, such as increased funding for cancer research and screening programs. Doing so will bring us closer to our vision of ending cancer as we know it, for everyone." All of the data in these reports can be accessed from the newly designed Cancer Statistics Center where you can view and download custom maps and graphs, such as a state-level comparison of smoking prevalence and lung cancer rates. This year's report also includes a special section: Cancer in People Who Identify as Lesbian, Gay, Bisexual, Transgender, Queer or Gender-nonconforming (LGBTQ+). The section is a summary of the latest information on the prevalence of major modifiable cancer risk factors and preventive measures, including screening in the LGBTQ+ populations, as well as challenges faced by LGBTQ+ individuals with cancer-based on current data. ACS author Angela Giaquinto also participated in the study. Cancer statistics 2024: All hands-on deck (editorial by Dr. Arif Kamal and Dr. Don Dizon, CA Editor-in-Chief and Editor) can be found here. About the American Cancer Society The American Cancer Society is a leading cancer-fighting organization with a vision to end cancer as we know it, for everyone. For more than 100 years, we have been improving the lives of people with cancer and their families as the only organization combating cancer through advocacy, research, and patient support. We are committed to ensuring everyone has an opportunity to prevent, detect, treat, and survive cancer. To learn more, visit cancer.org or call our 24/7 helpline at 1-800-227-2345. Connect with us on Facebook, Twitter, and Instagram. SOURCE American Cancer Society

Long-Term Safety and Efficacy Data from SIENDO Study in the TP53 Wild-Type Exploratory Subgroup Showed Signals of Improvement in Overall Survival (OS) Regardless of Mismatched Repair Status (MMR) Median OS Not Reached for Selinexor-Treated Patients Who are TP53 Wild-Type pMMR NEWTON, Mass., Nov. 6, 2023 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced the presentation of updated long-term safety and efficacy data from a pre-specified exploratory subgroup analysis of the SIENDO study (NCT03555422) in patients with advanced or recurrent TP53 wild-type endometrial cancer at the International Gynecological Cancer Society (IGCS) Annual Global Meeting in Seoul, South Korea. The primary analysis of the Phase 3 SIENDO study of selinexor maintenance therapy in advanced or recurrent endometrial cancer showed improvements in median progression-free survival (PFS) for the intent-to-treat (ITT) population but were not clinically meaningful. However, an exploratory analysis of a pre-specified subgroup of patients with TP53 wild-type endometrial cancer showed a promising efficacy signal. In the exploratory subgroup analysis, 113 patients with wild-type endometrial cancer received selinexor (n=77) or placebo (n=36) as maintenance therapy. Although the survival data are immature, as of the September 1, 2023, data cut-off date, the study showed an encouraging OS signal in the TP53 wild-type population: hazard ratio 0.76 (95% Confidence Interval [CI]: 0.36-1.59), with median OS not reached in either arm after a median follow up of 28.9 months. Similarly, encouraging preliminary OS was observed in patients with TP53 wild-type/pMMR endometrial cancer: hazard ratio 0.57 (95% CI: 0.24-1.35), with median OS not reached in selinexor arm, and 35 months in placebo arm after median follow-up of 31.6 months , and a HR of 0.62 (95% CI: 0.06-6.81), with median OS not reached in either arm after median follow-up of 27.3 months in patients with TP53 wild-type/dMMR endometrial cancer. "The preliminary OS data from this exploratory subset analysis of the SIENDO study corroborate the PFS results observed, which is compelling in this novel biomarker-driven population with high unmet need," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "These results showcase selinexor's potential as a foundational treatment for patients with TP53 wild-type endometrial cancer. We look forward to additional data in the first half of 2025 from the company's ongoing pivotal Phase 3 trial that may support U.S. and global regulatory filings." No new safety signals were identified as of the last data cut-off date on September 1, 2023. The most common treatment-emergent adverse events (AEs) with selinexor treatment were nausea (90%), vomiting (60%), thrombocytopenia (42%) and diarrhea (42%), the majority of which were grades 1-2. Of note, the rate of nausea in the placebo patients was 34%, vomiting 11%, and diarrhea 37%. The most common reported grade 3-4 treatment-emergent AEs included neutropenia (18%), nausea (12%), and thrombocytopenia (10%). TEAEs leading to discontinuations in the selinexor group were reported in 16% of patients. Currently, there are no specific targeted therapies available for patients with TP53 wild-type endometrial cancer. Advanced and recurrent endometrial cancer is associated with a poor prognosis, including limited disease control for patients who relapse after first-line systemic treatment.1 There are about 16,000 patients diagnosed with advanced and recurrent endometrial cancer in the U.S. each year2. More than 50% of these patients have TP53 wild-type cancer.2,3 TP53 wild-type is observed in both pMMR and dMMR populations. Recently there has been progress in potential treatment options in the dMMR subgroup with new targeted treatments; however, a large unmet need continues to exist for pMMR and for TP53 wild-type endometrial cancer. "Given the unmet need that remains for patients whose disease is pMMR, I'm excited by the results demonstrating an encouraging, preliminary trend in OS, coupled with signals of improvement in disease progression," said Dr. Giovanni Scambia, oncology gynecologist at MITO and Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. "These results highlight the potential opportunity to further personalize therapies and provide a strong rationale to further evaluate selinexor as maintenance therapy in TP53 wild-type endometrial cancer in the ongoing Phase 3 trial". IGCS Oral Presentation Title : Selinexor maintenance for patients with TP53wt advanced or recurrent endometrial cancer: Long-term follow up of efficacy and safety subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study Presenter: Giovanni Scambia, MD, MITO and Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Session Title: Plenary 02: Changing the Landscape of Endometrial Cancer Date and Time : Sunday, November 5, 2023, 4:30pm - 5:30pm (GMT+9)/ 3:30am - 4:30am (ET) IGCS Poster Presentation Title : ENGOT-EN20/GOG-3083/XPORT-EC-042 A phase 3, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy for patients with P53 Wild-type, advanced or recurrent endometrial carcinoma Presenter: Brian Slomovitz, MD, Mount Sinai Medical center and Florida International University Date and Time : Sunday, November 5, 2023, through Tuesday, November 7, 2023 IGCS Industry Sponsored Symposium in Partnership with Gynecologic Oncology Group (GOG) Title : The evolving landscape in molecular-driven investigational therapies for advanced endometrial cancer Presenters: Bradley J. Monk, MD, US Cancer Associates; Domenica Lorusso, MD, PhD, Catholic University of Rome and Fondazione Policlinico Gemelli IRCCS; Ritu Salani, MD, MS, UCLA Medical Center Date and Time : Monday, November 6, 2023, 7:15am – 8:15am (GMT+9)/ 6:15pm - 7:15pm (ET) About the EC-042 Study EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind study evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The EC-042 study was initiated in November 2022 and is expected to enroll up to 220 patients who will be randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The primary endpoint of the study is progression free survival (PFS), as assessed by an investigator, with overall survival as a key secondary endpoint. Further, in connection with the EC-042 Study, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOne®CDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type. About the SIENDO Study Karyopharm's evaluation of selinexor to treat patients with TP53 wild-type advanced or recurrent endometrial cancer is supported by data from an exploratory subgroup analysis from its ongoing SIENDO Study, a European Network of Gynaecological Oncological Trial Groups (ENGOT)-led trial in collaboration with the Gynecologic Oncology Group (GOG) Foundation, Inc. The SIENDO Study is a multicenter, randomized, double-blinded Phase 3 study evaluating the efficacy and safety of oral selinexor versus placebo as a front-line maintenance therapy in patients with advanced or recurrent endometrial cancer following at least one prior platinum-based combination chemotherapy treatment (NCT03555422). Participants in this study with advanced or recurrent disease who had a partial response or a complete response after at least 12 weeks of taxane-platinum combination chemotherapy were randomized in a 2:1 manner to receive either maintenance therapy of 80 mg of selinexor or placebo taken once per week, until disease progression. The primary endpoint in the study was PFS from time of randomization until death or disease progression as assessed by an investigator, with the goal of the study demonstrating a HR of 0.6. In the first quarter of 2022, Karyopharm presented top-line data from the SIENDO study, including preliminary exploratory subgroup analyses. Selinexor-treated patients had a median PFS of 5.7 months compared to 3.8 months for patients on placebo in the full trial population, which was not clinically meaningful. Patients in the exploratory subgroup of TP53 wild-type advanced or recurrent endometrial cancer treated with selinexor had a median PFS of 13.7 months compared to 3.7 months for the exploratory subgroup patients on placebo. There were no new safety signals identified, and a discontinuation rate of 10.5% due to adverse events (AEs). The most common treatment-emergent AEs in the SIENDO study of any grade were: nausea (84%), vomiting (52%), constipation (37%) and thrombocytopenia (37%). The most common grade 3 treatment-emergent AEs were nausea (10%), neutropenia (9%), thrombocytopenia (7%) and asthenia (6%). About Endometrial Cancer Endometrial cancer is the most common cancer of the female reproductive organs in the U.S., with approximately 66,000 new cases expected in 2023 leading to nearly 13,000 deaths.4 In 2020, there were approximately 130,000 new cases and 29,000 deaths in Europe from endometrial cancer, while on a global scale there were 417,000 new cases and approximately 97,000 deaths.5 Since 2002, the incidence of new cases and deaths from endometrial cancer have risen.6 Risk factors include obesity, Type 2 diabetes, high-fat diets, use of tamoxifen and oral estrogens, and delayed menopause.7 There are no approved therapies in the maintenance setting for patients with advanced or recurrent endometrial cancer.8 About XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade® (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm's partners, Antengene, Menarini, Neopharm and FORUS, in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada. Please refer to the local Prescribing Information for full details. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326 Email: [email protected] SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care. Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors. Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care. Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care. Serious Infection: Monitor for infection and treat promptly. Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes. Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception. Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients. Use In Specific Populations Lactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit . To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or . About Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in oral Selective Inhibitor of Nuclear Export (SINE) compound technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications and has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and Mainland China. Karyopharm has a focused pipeline targeting multiple high unmet need cancer indications, including in multiple myeloma, endometrial cancer, myelodysplastic neoplasms and myelofibrosis. For more information about our people, science and pipeline, please visit , and follow us on Twitter at @Karyopharm and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with endometrial cancer; and expectations related to the clinical development of selinexor and potential regulatory submissions of selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor and eltanexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm's business, results of operations and financial condition; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2023, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this release are the property of their respective owners. References 1 Cosgrove C, Backes, F, O'Malley D. The Oncol. 2021;26:10441051. 2 Oaknin, A., Bosse T, Creutzberg C, et al. Ann Oncol. 2022;860-877. 3 Nakamura M, Obata T, Diakoku T, et al. Int J Mol Sci. 2019 Nov;20(21): 5482. 4 American Cancer Society, About Endometrial Cancer: (accessed July 14, 2023) 5 International Agency for Research on Cancer, World Health Organization. "Corpus uteri Fact Sheet." Cancer Today, 2020: (accessed July 14, 2023) 6 Seer Cancer Incidence Rate Estimates, National Cancer Institute. Bethesda, MD. (accessed July 17, 2023) 7 American Cancer Society, Endometrial Cancer Risk Factors. (accessed July 14, 2023) 8 Corr B, Cosgrove C, Spinosa D, et al. BMJ Medicine, 2022;1:e000152. SOURCE Karyopharm Therapeutics Inc.