Category: Cancer and neoplasms

– Regulatory Designation Includes Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis and Post-Polycythemia Vera Myelofibrosis – – Pivotal Phase 3 Study of Selinexor and Ruxolitinib in Treatment-Naïve Myelofibrosis Initiated in June 2023 – NEWTON, Mass., July 17, 2023 /PRNewswire/ — Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to the development program of selinexor for the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis. “Fast Track Designation for selinexor highlights its potential to address the unmet medical need in myelofibrosis, an important acknowledgement as we continue our pivotal Phase 3 study,” said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. “Selinexor’s unique mechanism of action, XPO1 inhibition, is a novel and potentially fundamental mechanism in myelofibrosis. We have been highly encouraged by the efficacy and safety data observed to date [in our Phase 1 study] with selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and believe selinexor has the potential to shift the treatment paradigm. We look forward to continued interaction with the FDA as we advance the development of this promising treatment for patients in need.” In June 2023, Karyopharm initiated a pivotal Phase 3 clinical trial (XPORT-MF-034) (NCT04562389) to assess the efficacy and safety of once-weekly selinexor 60 mg in combination with ruxolitinib in JAKi-naïve patients with myelofibrosis. Updated data from the Phase 1 study were presented at the American Association for Cancer Research Annual Meeting 2023, American Society of Clinical Oncology 2023 and European Hematology Association 2023, which showed rapid, deep and sustained spleen responses and robust symptom improvement in patients treated with selinexor 60 mg in combination with ruxolitinib as of the April 10, 2023 cut-off date. Top-line data from the Phase 3 study is expected in 2025. The Company plans to expand its clinical development program in myelofibrosis by investigating selinexor in other JAKi-naïve settings, such as novel combinations, to benefit the greatest number of patients. Fast Track Designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously. Features of Fast Track Designation include frequent interactions with the FDA review team, and if relevant criteria are met, eligibility for Priority Review and Rolling Review. Further information about the Phase 3 study can be found at www.clinicaltrials.gov. About Karyopharm TherapeuticsKaryopharm 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 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 www.karyopharm.com, and follow us on Twitter at @Karyopharm and LinkedIn. Forward-Looking StatementsThis 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 myelofibrosis; 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 March 31, 2023, which was filed with the Securities and Exchange Commission (SEC) on May 4, 2023, and in other filings that Karyopharm may make with

Today I am going to go over what I picked up from the American Hospital Association’s (AHA’s) Coding Clinic for the second quarter of 2023. It was chock-full of interesting advice. Two weeks ago, I went over COVID-19 screening. I think Coding Clinic should have explained why we continue to use Z20.822, Contact with and (suspected) exposure to COVID-19 after May 11, instead of just noting that “this advice is consistent with current coding guidance.” In theory, once there is no longer an epidemic or pandemic, we should be using “contact with” and “suspected exposure” only when we recognize that is the probable scenario. In practice, they are setting the timeline as the end of the fiscal year in which the pandemic ended (that is, 2023). I learned a new code in my review! There is a code, R97.21, Rising PSA following treatment for malignant neoplasm of prostate. This offers a solution on how to code biochemically recurrent prostate cancer, post-prostatectomy, and salvage radiation therapy. The Coding Clinic indicated that, since the prostate had been resected, the culprit has to be a metastasis, and since the site is unknown, you can use C79.9, Secondary malignant neoplasm of unspecified site. My new code is also used because that was how they diagnosed it – that is what “biochemically recurrent” means. A question was posed regarding a patient getting a workup for a suspected malignancy, when an excisional biopsy of a supraclavicular lymph node revealed metastatic non-small cell lung cancer. The question related to the sequencing of the primary and secondary malignancies. Although the procedure is ostensibly linked to the secondary malignancy, the primary malignancy is the condition responsible for both the metastasis and the overall workup/hospital admission. The response is to sequence the primary lung cancer as principal diagnosis (PDx). One should only sequence metastasis as PDx if it is the only focus for diagnostic or therapeutic treatment. An interesting question was asked about venous thoracic outlet syndrome causing left upper extremity swelling and acute left subclavian deep vein thrombosis. The indexing led to G54.0, Brachial plexus disorders, but the questioner proposed I87.1, Compression of vein, as a more accurate clinical representation. The reviewer agreed that since the pathology involved the vein, not nerves, further research should lead the coder to I87.1. To my clinician brain, “compression” usually indicates external forces impacting on the anatomy, like a tumor pressing on the trachea. However, ICD-10-CM indexes kink, obstruction, stenosis, and stricture to “compression of vein,” too. On page 10, there is a question about a patient with pre-existing Type 2 diabetes presenting with hyperglycemia believed to be secondary to autoimmune diabetes after initiation of immunotherapy medication. The answer was to use only E11.65, Type 2 DM with hyperglycemia and T45.1X5A, Adverse effect of antineoplastic and immunosuppressive drugs, initial encounter, for the exacerbation of the disorder of sugar metabolism. I couldn’t help but wonder – where would you go if there were no underlying, pre-existing Type 2 diabetes? In that case, the diabetes code would be E09.65, Drug or chemical induced diabetes mellitus with hyperglycemia. Page 15 features a question about a post-abortion complication. A patient presents for an elective termination of pregnancy due to a genetic abnormality and sustains uterine atony and hemorrhage. If there were a post-abortion code analogous to O72.1, Other immediate postpartum hemorrhage, that would be the right choice. However, since there is not, the advice is to use O04.6, Delayed or excessive hemorrhage following (induced) termination of pregnancy, plus the code for the maternal care for the chromosomal abnormality. Currently, there is an Excludes1 note at O04 precluding concomitant use of Z33.2, Encounter for elective termination of pregnancy, but this will become an Excludes2 on Oct. 1. For this particular code, it makes sense, because excessive hemorrhage could occur at the time of the encounter for the termination (or could be delayed until a subsequent visit). My final comment is that the reason why linkage is assumed resulting in the “with” guidance is that the conditions with the assumed causal relationship are commonly associated, not because the ICD-10-CM classification mandates it. It is the other way around; ICD-10-CM acknowledges the near-inevitable relationship between, for instance, hypertension and heart failure, or diabetes and chronic kidney disease, by assuming causality unless specified otherwise. The words “due to” do establish the relationship if the provider documents them (e.g., hypertension due to hyperthyroidism à I15.2, Hypertension secondary to endocrine disorders). Please review the Coding Clinic guidance yourself. There are more nuggets to collect. And I’d like to extend an invitation to all to join me on LinkedIn on Thursday at 1:30 p.m. EST for my next “Ask Dr. Remer.” You can find the link on my company page, Erica Remer, MD, Inc. Hope to see you then.

In early 2023, I had my first-ever colonoscopy. I was 68. My wife had been pushing me to get one for several years, but I felt fine and didn’t have any symptoms, so I didn’t think I needed one. To make her happy and to give myself peace of mind, I finally decided to schedule the colorectal cancer screening. The hardest part for me was drinking the bowel prep. The procedure itself was easy; it just felt like a great nap. But when I woke up, my doctor said that he had found a tumor and it was likely cancerous. A CT scan confirmed that I had a tumor, but it didn’t appear to have spread. My wife advised me to make an appointment at MD Anderson. I hesitated because of the distance between Houston and our home in Brownsville, Texas. I’m a college professor, and I felt like I wouldn’t have time for the travel. But my wife told me, “You’ve got the finest cancer hospital up the road. Go.” I knew she was right, so I called and made an appointment. Colorectal cancer surgery at MD Anderson From the moment I first walked into MD Anderson West Houston, I was so impressed. The hospital was beautiful, welcoming and technologically advanced. Even the architecture made me feel like I had walked into the future, which gave me a sense of calm. I knew I was in the right place. I had my first appointment with a colorectal surgeon. What struck me about the doctors and nurses at MD Anderson was their empathy – they listened more than they talked. They told me with confidence that I was going to be fine. Additional imaging confirmed my diagnosis: sigmoid adenocarcinoma. In March 2023, I had laparoscopic surgery at MD Anderson’s Texas Medical Center Campus to remove the tumor. I was able to avoid an ostomy bag because of the tumor’s location. I recovered quickly from surgery. The surgery was in the morning and by that evening I was walking around on my floor of the hospital. Within a week, I was able to drive my wife and myself back home and was shocked to feel quite normal. Teaching my students about the importance of colonoscopies During surgery, my surgeon discovered that the tumor had penetrated the wall of my colon and that a few lymph nodes were affected. This meant the cancer was stage III. To make sure there weren’t any remaining cancer cells, it was recommended I also undergo chemotherapy. Kaysia Ludford, M.D., has coordinated my chemotherapy treatments with a local doctor so I can be closer to home. I started a FOLFOX chemotherapy regimen in June. It hasn’t been easy, and I’ve realized I need to rest for a few days after treatment. The current plan is for me to receive chemotherapy through October. I get an infusion every three weeks and take pills at home on a schedule of two weeks on and one week off. I know that colon cancer is showing up in younger people, so I tell my students to not make the mistake I did and put off getting a colonoscopy. My surgeon told me I’d likely had this tumor for many years. If I’d gotten a colonoscopy earlier, I might have avoided all of this. Request an appointment at MD Anderson online or by calling 1-877-632-6789.

Background Diffuse large B cell lymphoma (DLBCL) is the most common B lymphoid malignancy disorder, representing more than 30% of non-Hodgkin’s lymphoma.1 Although typical morphology is characterized by the diffuse or sheet-like proliferation of mature large B cells, DLBCL is a class of highly heterogeneous diseases exhibiting varying clinical and biological performances.2 DLBCL typically originates from the lymph nodes, bone marrow and immune-privileged tissue, and 20–40% of all cases of DLBCL initially have extranodal involvement.3 In the last decade, intensive research indicated that extranodal DLBCLs should be considered distinct entities with strikingly different molecular pathogenesis, prognosis and clinical presentation. Primary extranodal DLBCL commonly presents in the stomach, mediastinum, central nervous system, and testicle, among which the penis remains rare.4 Most of the reported primary lymph malignant of the penis sited in the penile shaft and/or the glans penis without specific symptoms,5 exhibiting penile masses, nodules, diffuse swelling, refractory erosions and ulcers,5–14 and dysuria occurs when lymphoma masses compress the urethra.15–18 There are also cases of penile erectile dysfunction, penis swelling and other clinical manifestations.19 Diagnosing is very difficult, and patients often are misdiagnosed, leading to delayed treatment. In the meantime, therapeutic options for primary DLBCL of the penis have been controversial due to the limited number of patients and treatment-related sequelae. While DLBCL has been studied extensively, less is known about the primary DLBCL of the penis due to the small number of cases reported. We described the case of an 86-year-old man with primary DLBCL of the penis identified in our hospital and performed a review of the literature on the character of treatment and prognosis. Case An 86-year-old man was referred to our hospital due to excessive foreskin and 9 months of penile head erosion in December 2016. Physical examination showed a circle of ulceration on the penis head about 1.0 cm wide, with mild tenderness and no obvious secretion. There was no weight loss, fever, night sweats, chills, fatigue or shortness of breath. Routine laboratory tests showed normal red blood cells, white blood cells and platelet counts. Prepuce circumcision under local anesthesia and penis biopsy was performed after primary consideration of penile mass and prepuce glans inflammation. Under the pathological examination of the squamous epithelium and necrotic tissue after the biopsy, the tumor cells were ovoid, with large nuclei, obvious nucleoli, sparse cytoplasm and patchy, diffuse infiltrating growth (Figure 1). Immunohistochemistry presented diffuse positivity for CD20 and PAX-5 in large lymphoid cells, while c-myc, BCL-2, BCL-6 and MUM-1 were partly positivity. The tumor cells were negative for CD5, CD10, Cyclin D1, CD56, CD23, CK, F8, P16, P40, CD34 and CD31. The Ki-67 index was positive in 50% of the tumor cells. Negative for in situ hybridization EBER were noted. FISH analysis showed no rearrangement of BCL6, BCL2 or c-MYC genes. Pathological revealed diffuse large B cell lymphoma (non-germinal center type subtype). A positron emission tomography computerized tomography revealed the remarkable focal hypermetabolism (max SUV 12.6) on the head position at the penis, with a size of about 31 × 30 mm (Figure 2a and b). He had bladder cancer before and was treated with electric resection of bladder cancer combined with chemotherapy, sustained remission during the 6-year follow-up. According to ESMO guidelines,3 this patient was comprehensively diagnosed as primary DLBCL of the penis, non-germinal center type (Ann Arbor stage IE stage A group, IPI score 1 point, low-risk group). Figure 1 (a) Tumor cells are arranged in a sheet, diffuse infiltration and growth. HE stain. X20. (b) Most of the infiltrating lymphoid cells show positive Immunoreactivity staining for CD20. Immunohistochemical stain. X20. Figure 2 The images before and after chemotherapy. (a and b) Baseline positron emission tomography-computed tomography showing the penile round soft tissue mass with size of about 31*30mm with intense F-18 fluorodeoxyglucose uptake. (c and d): Transaxially and sagittal magnetic resonance imaging revealing the mass of the glans penis about 23×33×26 mm after 3 cycles of chemotherapy. The patient has managed with R-COP (Rituximab Cyclophosphamide, Vincristine and Prednisolone) chemotherapy for two cycles and one R-miniCHOP (R-COP plus liposome doxorubicin). After 3 cycles of chemotherapy, the mass of the glans penis was revalued by MRI with a size of 23 × 33 × 26 mm (Figure 2c and d), revealing partly remission. Considering the insensitive to chemotherapy, subtotal penectomy was performed in the urology department. Postoperative pathological examination showed diffuse distribution and invasive growth of heterotypic lymphoid cells under the squamous epithelium. Pathological diagnosis (glans penis) showed DLBCL with ulceration formation, tumor tissue involved in the spongy body and urethral mucosa, and no involvement in the cutting margin, same as the first. No chemotherapy or radiotherapy was proceeding. The patient achieved complete remission (CR) after surgery and sustained remission until now. Discussion Primary DLBCL of the penis is a very rare entity with no specific clinical presentation, standard treatment and predictable outcome. The pathophysiology is not fully understood, as the pathogenesis and gene background might keep similar to other extranodal lymphomas or not that is unknown. The definitive diagnosis primarily depends on the pathological because of the absence of specific clinical manifestations and radiological features. Moreover, the treatment cannot be standardized, and the prognosis cannot be revalued due to the inadequate cases reported. In our case, we observed a gradual change of mucosa; surgery subtotal penectomy was performed to get remission after chemotherapy failed. To our knowledge, few similar cases have been reported in the literature. The first case of primary DLBCL of the penis was reported in 1988,6 and until now, only 19 cases of primary DLBCL of the penis have been reported in the literature (Table 1). The main clinical characteristics were summarized in Table 1 and Table 2, including our case. The median age was 69 years (range: 42–86 years), and only 3 patients were younger than 60, which suggests such cases were predominantly in the elderly. Among them, stage IE patients accounted for 63.2% of the total and stage IV was not reported, indicating most DLBCL originated from the penis remain

Alfa Lafleur, APRN Nurses play a crucial role in managing symptoms experienced by patients with myeloproliferative neoplasms (MPNs) — a group of blood cancers that cause the bone marrow to overproduce red or white blood cells or platelets. “MPNs are rare, and the nurse/nurse practitioner [must] take the time to listen to the patients and educate them about symptom management,” Alfa Lafleur, APRN, from Florida Cancer Specialists and Research Institute Trinity Cancer Center in Trinity, Florida, told Oncology Nursing News®. Even though the MPN category includes a range of diseases such as myelofibrosis, essential thrombocythemia, and polycythemia vera, patients with MPNs experience several common symptoms. Lafleur said she likes to think of those symptoms in categories. First, Lafleur explained, there are the inflammation-related symptoms including weight loss, night sweats, fever, fatigue and a general feeling of unwellness. Then, there are the microvascular-related symptoms related to dysregulation of the JAK2 pathway, which can cause numbness in the hands and feet as well as headaches, vision changes and a painful rash. There are also symptoms related to the enlargement of the patient’s spleen, including fullness, pain and discomfort in the upper left quadrant of the abdomen. As MPN symptoms typically intensify over time, with patients potentially experiencing long asymptomatic periods, the symptom identification and management work of a nurse is of particular importance. “The nurse remains vigilant in assessing for symptoms as early identification that the disease may be worsening or transforming (which) can result in improved patient outcomes,” Lafleur said. It’s also important for patients to keep tabs on their symptoms, as the MPN Research Foundation explains on its website. “Because symptoms can vary significantly among MPN patients, it is important to track changes in symptoms and their severity between doctor visits,” the foundation states. “Keep current on the latest MPN research updates and speak to your doctor about how changes in your symptoms may call for a change in treatment.” Resources are available for both patients and providers. Lafleur cited the MPN Research Foundation’s education for providers and patient support hotlines staffed by counselors who can in turn provide emotional support and assistance in locating additional resources and support groups. Additionally, Voices of MPN, she said, “has a phenomenal app that helps the patient to track their symptoms, educates on the disease process and offers other resources and support to the patient.” Patients with MPNs, Lafleur noted, can live with their cancer for years as they undergo different treatments that are each associated with side effects and symptoms — an experience that, she said, “can be really frustrating and upsetting” — and can be accompanied by fear of MPNs’ potential transformation into more aggressive forms of cancer such as leukemia or the risk of experiencing amyocardial infarction or cerebral vascular accident, or CVA, also known as a stroke. Lafleur has some straightforward guidance for patients: “My best advice to patients is to remind them that they are not alone in this disease,” she said. “No symptom is too small to bring to the attention of your nurse who is more than willing to assist with the physical and mental challenges that come.” Reference MPN Research Foundation. Accessed July 25, 2023. https://www.mpnresearchfoundation.org/

Specialty

Signal of PFS Improvement in SIENDO for Selinexor-Treated Patients was Observed Only in Subgroup Who are TP53 Wild-Type with a Median Progression-Free Survival of 27.4 Months Median PFS Not Reached for Selinexor-Treated Patients Who are TP53 Wild-Type MSS (pMMR) Updated Analysis Provides Further Rationale for XPORT-EC-042, the Ongoing Pivotal Phase 3 Study (NCT05611931) Evaluating Selinexor as Maintenance Therapy in TP53 Wild-Type Endometrial Cancer NEWTON, Mass., July 25, 2023 /PRNewswire/ — Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced the presentation of updated exploratory subgroup analyses from the SIENDO study (NCT03555422) in patients with advanced or recurrent TP53 wild-type endometrial cancer at the virtual American Society of Clinical Oncology (ASCO) Plenary Series. 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 TP53 wild-type is found in approximately 50% of advanced/recurrent tumors in patients with endometrial cancer.2,3 TP53 wild-type is observed in both MSS (pMMR) and MSI-H (dMMR) populations. Recently there has been progress in potential treatment options in the MSI-H (dMMR) subgroup with new targeted treatments. However, a large unmet need continues to exist for MSS (pMMR), which comprises approximately 70% of all endometrial cancer patients and of that population, approximately 70% are TP53 wild-type. 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 SIENDO study, 263 patients were randomly assigned, with 174 patients allocated to the selinexor arm and 89 patients to the placebo arm. One hundred and thirteen patients with TP53 wild-type endometrial cancer were randomized to receive selinexor (n=77) vs placebo (n=36) as maintenance therapy. As of the March 30, 2023 data cut-off date, and a median duration of follow-up of 25.3 months, selinexor-treated patients with TP53 wild-type endometrial cancer had a median PFS of 27.4 months compared to 5.2 months for patients with TP53 wild-type endometrial cancer receiving placebo. Additionally, median PFS was not reached for selinexor-treated TP53 wild-type MSS (pMMR) endometrial cancer patients compared to 4.9 months for TP53 wild-type MSS (pMMR) endometrial cancer patients treated with placebo. No new safety signals were identified as of the last data cut-off date on March 30, 2023. The most common adverse events (AEs) in TP53 wild-type patients were nausea (91%), vomiting (61%) and diarrhea (40%), the majority of which were grades 1-2. The most common reported grade 3-4 treatment-emergent AEs (TEAEs) included neutropenia (18%), nausea (12%), and thrombocytopenia (9%). TEAEs leading to discontinuations were reported in 16% of patients. The SIENDO exploratory subgroup data provides further rationale for the ongoing pivotal Phase 3 study (XPORT-EC-042; NCT05611931) of selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer with the strongest signal in TP53 wild-type, MSS (pMMR). Karyopharm is currently enrolling patients in the pivotal Phase 3 study of selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (XPORT-EC-042; NCT05611931) to better understand the exploratory subgroup analysis. This trial includes a companion diagnostic tool under development by Foundation Medicine, Inc. 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. “The updated results from SIENDO suggest that selinexor may have the potential to prolong systemic therapy response in patients whose disease is TP53 wild-type. Particularly encouraging are the data observed in the subgroup of patients whose disease are both TP53 wild-type and MSS,” said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. “We are encouraged by the updated results from this study as it further strengthens the rationale for our ongoing EC-042 Phase 3 study.” “Treatment options for women with advanced or recurrent endometrial cancer are rapidly evolving with the identification of molecular subgroups. Limited options, however, still persist among certain subgroups, including patients with mismatch repair-proficient disease (pMMR), who comprise about 70% of endometrial cancers,” said Dr. Ignace Vergote, principal investigator and gynecologist oncologist, ENGOT and the Belgium and Luxembourg Gynaecological Oncology Group (BGOG), University of Leuven, Leuven Cancer Institute, Leuven, Belgium. “TP53 is a well-recognized molecular marker in endometrial cancer. About 50% of patients with advanced, recurrent endometrial cancer have disease identified as TP53 wild-type and about 70% of those further classified as a pMMR. The EC-042 study is designed to show that inhibition of XPO1 with selinexor may provide a potential new therapeutic option for these patients.” “The long-term follow-up in the TP53 wild-type subgroup from the SIENDO trial is extremely encouraging and suggests that TP53 status could be an important biomarker that can identify patients who benefit from XPO1 inhibition with selinexor,” said Dr. Brian Slomovitz, Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center, and Uterine Cancer Trial Advisor for GOG Partners, Inc. “Given the unmet need that remains for patients whose disease is pMMR as well as the encouraging exploratory data in the subgroup of patients who are classified as TP53 wild-type and pMMR, a potential new paradigm for both the diagnosis and treatment of women with endometrial cancer may be identified. I look forward to the ongoing progress of EC-042 to further explore this hypothesis.” ASCO Plenary Series ProgramTitle: Long-term follow up of selinexor maintenance in patients with TP53wt advanced or recurrent endometrial cancer: A pre-specified subgroup analysis from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study.Presenter: Brian Slomovitz, MD, Mount Sinai Medical CenterSession Date and Time: Tuesday July 25, 2023, 3:00pm – 4:00pm (ET)This livestream event presented by ASCO is free to register at:https://old-prod.asco.org/meetings-education/monthly-plenary-series/program About the EC-042 StudyEC-042 (XPORT-EC-042; NCT05611931) is a global, Phase

R. Lor Randall, MD, FACS Despite being considered a rare, noncancerous bone tumor, chondrosarcoma often necessitates aggressive treatment due to its potential for metastasizing. Accordingly, it is vital to confidently differentiate patients with chondrosarcoma from those with bone malignancies in clinic, particularly when it comes to atypical disease presentations, says R. Lor Randall, MD, FACS. “We’re talking about an uncommon tumor with [some] uncommon presentations. It’s something that doesn’t get a lot of attention in the oncology world but might be [a condition] that people should know about,” said Randall, the David Linn Endowed Chair for Orthopedic Surgery, the chair of the Department of Orthopedic Surgery, and a professor at UC Davis Comprehensive Cancer Center in Sacramento, California. In an interview with OncLive®, Randall explained the difference between noncancerous chondroblastoma and other bone neoplasms, detailed the typical diagnosis and treatment of this rare condition, and emphasized the importance of pediatric and medical oncologists being able to identify it in clinic. OncLive: What is chondroblastoma, and how does it differ from other hematologic malignancies? Randall: Chondroblastoma is not a malignancy. It’s a benign tumor of the bone usually in young people, but it can mimic an aggressive bone neoplasm in appearance. Chondroblastoma is a somewhat aggressive benign neoplasm of bone, meaning it must be treated aggressively with surgery sometimes; however, radiographically and imaging-wise, it could be confused for something like a bone malignancy. It is possible that medical oncologists or other types of oncologists beyond orthopedic oncologists might see someone with a potential chondroblastoma. It’s important to realize that these are very rare [neoplasms], and they make up less than 1% of all bone tumors. They tend to [present] in young people and tend to [occur] in the epiphysis or apophysis of a skeletally immature person. How is chondroblastoma typically diagnosed? The workup usually [involves] referral to an orthopedic oncologist, who in their expertise will probably be able to determine whether this is a chondroblastoma and then treated surgically. A very small number of patients can go on to develop recurrences in the same area, and there have been some sparse case reports of it spreading in a benign way to the lungs. We’ve recently published a couple of papers [on unusual chondroblastoma cases]. One was [published] by me [and detailed an incidence of] chondroblastoma that was recurrent in the pelvis of an older person. [This was] unusual in that it’s [in an] older [person] and [located] in the pelvis. My partner [published a case study of] one in the finger, and it’s not very common in the finger. Why is chondroblastoma more frequently observed in younger patients? We don’t know the medical answer to that, per se, but we think it probably has to do with the fact that these patients are skeletally immature, and their growth plate is very active. There might be some sort of inclusion cyst of the growth plate in the epiphysis leading to this sort of satellite area in the bone. What is the typical management approach for this condition? Does the treatment of chondroblastoma differ when dealing withunusual presentations? Generally speaking, they’re treated with surgical removal, and there’s different ways by which that is done. They tend to arise in anatomically-challenging areas, [particularly] between a joint and a growth plate where there’s not a lot of room for error. You don’t want to create any damage to the growth plate or to the joint, and you have to be very strategic and precise in how you go after these. It does lend itself to management with techniques such as surgical navigation, computerized navigation, and other techniques that have come online in the past 5 to 10 years. [These] enable the surgeon to be much more precise in their surgical ablation of [chondroblastomas]. Given the rarity of this condition, can chondroblastoma mimic any other conditions? Because chondroblastomas evolve in a very distinct part of the bone in a young person, the differential diagnosis is relatively limited. If it arises in an adult or it’s very advanced, things like osteosarcoma, Ewing sarcoma, and other types of bone sarcomas would be in the differential diagnosis. At this time, is there any ongoing or planned research focused on chondroblastoma? There may be some research on applied surgical techniques. Although we don’t understand the entire pathophysiology [of chondroblastoma], it’s rare and treatable enough that there’s not a lot of laboratory research going into it. Because of its anatomic location, many surgical oncologists, particularly orthopedic oncologists, are using some of the latest applications in technology to treat these in that scenario of investigation. What is your main takeaway message for academic and community oncologists who might not see this condition very often? Particularly for the pediatric oncologists, if they are seeing someone with a destructive lesion in the bone that is in the epiphysis, which is the area right underneath the joint space, they should [consider] chondroblastoma. Obviously, they’ll confer with the radiologists and orthopedic oncologists, but it is something to consider.If [they are] referred a patient with a destructive lesion in this area, they should be able to counsel patients that there are benign things that can look like this, as chondroblastoma is benign. [They can tell these patients] not to be too alarmed, but that we must establish the diagnosis. In the grand scheme of things, there are very rare case reports of chondrosarcoma expanding into the lungs and things of that sort. If a medical oncologist or pediatric oncologist is seeing someone with a chondroblastoma, performing at least a chest radiograph is not inappropriate if there are concerns about aggressiveness.

Isabelle Franklin, medical student, Kaiser Permanente Bernard J. Tyson School of Medicine, discusses strategies healthcare providers can implement to address or ameliorate disparities in place that are affecting screening rates in colorectal cancer (CRC). Findings from a cross-sectional study on the effect of social determinants of health on CRC screening rates at Kaiser Permanente were presented at the 2023 ASCO Annual Meeting. Of the 3,443 patients who completed the Kaiser Permanente National Social Needs Survey in 2020, a significant correlation between unmet self-reported social needs and lower rates of screening was identified. These self-reported social needs included severe financial strain, feelings of social isolation, and food insecurity. Moreover, patients who were advanced in age, who were not insured, and those whose primary language was not English had lower CRC screening rates, indicating the correlation between demographic factors and CRC screening completion. These findings indicate the importance of investing in social and hospital-led programs to mitigate barriers to screening completion in CRC. To do so, it is first necessary to obtain information on a patient’s potential disparities early on, Franklin states. This can be done through intake screening survey when patients arrive at the clinic, or by requiring providers to ask their patients about any challenges accessing care during the visit, Franklin suggests. Once a patient’s needs have been identified, providers should implement measures, identify local organizations, and share appropriate resources to help patients meet their basic needs, Franklin continues. At Kaiser Permanente, the pilot program, Thrive Local, has been developed to help providers ensure their patients’ have knowledge of and access to community resources and organizations, Franklin details. Thrive Local involves the use of a database containing this information that can be filtered by type of social need and by a patient’s zip code, she explains. Furthermore, its integration with patients’ electronic health records allows providers to directly refer their patients to these organizations using the patient portal. This allows providers to receive real-time confirmation that their patients have connected with the recommended resources, Franklin concludes.

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