A Phase II Study of Fulvestrant plus Abemaciclib in Hormone Receptor-Positive Advanced or Recurrent Endometrial Cancer.

Purpose: Inhibition of the cyclin D-cyclin dependent kinase (CDK)4/6-INK4-retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy. Responses to endocrine monotherapy in advanced endometrial cancer (EC) are suboptimal, perhaps due to genomic alterations that promote estrogen receptor (ER)-independent cyclin D1-CDK4/6 activation. We hypothesized that addition of abemaciclib, a CDK4/6 kinase inhibitor, to antiestrogen therapy with fulvestrant will be an effective therapeutic strategy in patients with advanced or recurrent EC.

Histology-Specific Clinical Trial of Lenvatinib and Pembrolizumab in Patients with Sarcoma.

Purpose: Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes to its antitumor effects.

Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial.

Objective: Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity.

A phase 2 trial of zanidatamab in HER2-overexpressed advanced endometrial carcinoma and carcinosarcoma (ZW25-IST-2).

Objective: HER2 overexpression is associated with decreased overall survival in metastatic endometrial cancer. Trastuzumab with chemotherapy has demonstrated efficacy for first-line management of advanced HER2+ endometrial carcinoma, but HER2-directed therapy in the recurrent setting is limited. Zanidatamab (ZW25), a humanized, bispecific antibody that simultaneously binds the 2 distinct HER2 epitopes bound by trastuzumab and pertuzumab, has demonstrated safety and activity in HER2+ tumors.

Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets.

Purpose: Tumor genomic profiling is increasingly used to guide treatment strategy in patients with cancer. We integrated tumor genomic, clinical demographic, and treatment response data to assess how prospective tumor-normal sequencing impacted treatment selection in patients with cervical cancer.

Experimental Design: Cervical cancers were prospectively analyzed using the MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel.

Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission.

We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms' Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti-PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity.

Durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial cancer or endometrial carcinosarcoma: A randomized open-label phase 2 study.

Introduction: Our understanding of the biologic heterogeneity of endometrial cancer has improved, but which patients benefit from single-agent versus combination immune checkpoint blockade remains unclear.

Methods: We conducted a single-center, randomized, open-label, phase 2 study of durvalumab 1500 mg (Arm 1) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks (Arm 2) in patients with endometrial carcinoma. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS) at 24 weeks.

Effects of Vigorous Versus Restorative Yoga Practice on Objective Cognition Functions in Sedentary Breast and Ovarian Cancer Survivors: A Randomized Controlled Pilot Trial.

Purpose: Many cancer survivors experience cancer-related cognitive impairment (CRCI). We conducted a randomized controlled pilot trial of 2 types of yoga practice and evaluated their effects on participants' objective cognitive function.

Methods: Sedentary breast or ovarian cancer survivors were randomized to practice either restorative yoga (with more meditative practice and minimal physical exertion) or vigorous yoga (with considerable physical exertion and minimal meditative practice) in 60-minute supervised sessions 3 times a week for 12 weeks, followed by 12 weeks of home practice.

Central retinal vein occlusion in the setting of fibroblast growth factor receptor inhibition.

Purpose: To report a case of central retinal vein occlusion (CRVO) in a patient being treated with a fibroblast growth factor receptor (FGFR) inhibitor.

Observations: A 54-year-old female patient with endometrial cancer presented with CRVO and cystoid macular edema while receiving lenvatinib/pembrolizumab combination therapy. The patient received treatment with intravitreal bevacizumab, after which her visual acuity improved markedly, permitting the continuation of her chemotherapy regimen without recurrence of ocular adverse events.

Molecular Subclasses of Clear Cell Ovarian Carcinoma and Their Impact on Disease Behavior and Outcomes.

Purpose: To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes.

Experimental Design: We profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival.

Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination.

Background: To characterize the safety, immunogenicity, and outcomes of patients with high-grade serous ovarian cancer (HGSOC) in second or greater remission treated with a polyvalent antigen-KLH plus OPT-821 vaccine construct and bevacizumab.

Methods: Patients with recurrent HGSOC were treated with the vaccine plus bevacizumab at our institution from 01/05/2011 to 03/20/2012. Follow-up continued until 03/2021.

Treatment of ovarian clear cell carcinoma with immune checkpoint blockade: a case series.

Background: Although immune checkpoint blockade has demonstrated limited effectiveness against ovarian cancer, subset analyses from completed trials suggest possible superior efficacy in the clear cell carcinoma subtype.

Objective: To describe the outcomes of patients with ovarian clear cell carcinoma treated with immune checkpoint blockade.

Methods: This was a single-institution, retrospective case series of patients with ovarian clear cell carcinoma treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor with or without concomitant cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition between January 2016 and June 2021.

DNA Methylation Profiles of Ovarian Clear Cell Carcinoma.

Background: Ovarian clear cell carcinoma (OCCC) is a rare ovarian cancer histotype that tends to be resistant to standard platinum-based chemotherapeutics. We sought to better understand the role of DNA methylation in clinical and biological subclassification of OCCC.

Methods: We interrogated genome-wide methylation using DNA from fresh frozen tumors from 271 cases, applied nonsmooth nonnegative matrix factorization (nsNMF) clustering, and evaluated clinical associations and biological pathways.

Spectrum of Mutations and Gene Rearrangements in Ovarian Serous Carcinoma.

Unlabelled: Low-grade serous carcinoma (LGSC) is a rare type of ovarian cancer, which commonly arises from serous borderline tumor (SBT) and is characterized by frequent activating mutations in the mitogen-activated protein kinase pathway, including . The mutation is associated with improved prognosis in SBT and LGSC, and responses to BRAF inhibitor therapy have been reported. We sought to characterize the clinicopathologic and molecular features of -driven tubo-ovarian and primary peritoneal serous tumors.

TSC2-mutant uterine sarcomas with JAZF1-SUZ12 fusions demonstrate hybrid features of endometrial stromal sarcoma and PEComa and are responsive to mTOR inhibition.

Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression.

The effects of neoadjuvant chemotherapy and interval debulking surgery on body composition in patients with ovarian cancer.

Background: The aim of this study was to quantify changes in body composition during ovarian cancer treatment and relate these changes to rates of complete gross resection (CGR).

Methods: One hundred two patients with stage III or IV ovarian cancer who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery were a part of a prospectively collected database that included computed tomography scans at three time points-diagnosis, following NACT, and following debulking surgery. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue volumes were obtained from a 30-mm volumetric slab beginning at the third lumbar vertebrae.

Sustained response to lenvatinib and pembrolizumab in two patients with -mutated endometrial mesonephric-like adenocarcinoma.

•Endometrial mesonephric-like adenocarcinoma (MLA) is a rare and aggressive subtype of epithelial endometrial cancer.• mutations are characteristic in patients with endometrial MLA.•We report two cases of -mutated endometrial MLA with excellent and durable responses to lenvatinib and pembrolizumab.

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study.

Purpose: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery.

Materials And Methods: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery.

Mesonephric and mesonephric-like carcinomas of the female genital tract: molecular characterization including cases with mixed histology and matched metastases.

Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically similar, do not have obvious Wolffian derivation. Here, we sought to characterize the repertoire of genetic alterations in primary mesonephric and mesonephric-like carcinomas, in the distinct histologic components of mixed cases, as well as in matched primary tumors and metastases.