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This article reviews treatments and targets of interest in endometrial cancer by molecular subtype. The Cancer Genome Atlas (TCGA) classifies four molecular subtypes—mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H); copy number high (CNH)/p53abn; copy number low (CNL)/no specific molecular profile (NSMP); and POLEmut—which are validated and highly prognostic. Treatment consideration by subtype is now recommended. In March and April 2022, respectively, the US Food and Drug Administration (FDA) fully approved and the European Medicines Agency adopted a positive opinion recommending the anti-programmed cell death protein-1 (PD-1) antibody pembrolizumab for advanced/recurrent dMMR/MSI-H endometrial cancer which has progressed on or following a platinum-containing therapy. A second anti-PD-1, dostarlimab, received accelerated approval by the FDA and conditional marketing authorization by the European Medicines Agency in this group. The combination of pembrolizumab/lenvatinib for mismatch repair proficient/microsatellite stable endometrial cancer, including p53abn/CNH and NSMP/CNL, received accelerated FDA approval in conjunction with Australia’s Therapeutic Goods Administration and Health Canada in September 2019. The FDA and European Medicines Agency made full recommendations in July 2021 and October 2021. Trastuzumab is National Comprehensive Cancer Network (NCCN) compendium listed for human epidermal growth factor receptor-2-positive serous endometrial cancer, which is primarily within the p53abn/CNH subtype. In addition to hormonal therapy, maintenance therapy with selinexor (exportin-1 inhibitor) showed potential benefit inp53-wildtype cases in a subset analysis and is being investigated prospectively. Other treatment regimens being evaluated in NSMP/CNL are hormonal combinations with cyclin-dependent kinase 4/6 inhibitors and letrozole. Ongoing trials are evaluating immunotherapy in combination with frontline chemotherapy and other targeted agents. Treatment de-escalation is being evaluated in POLEmut cases given its favorable prognosis with or without adjuvant therapy. Molecular subtyping has important prognostic and therapeutic implications, and should guide patient management and clinical trial design in endometrial cancer, which is a molecularly driven disease.

Patients with gynecologic malignancies may have varied responses to COVID-19 infection. We aimed to describe clinical courses, treatment changes, and short-term clinical outcomes for gynecologic oncology patients with concurrent COVID-19 in the United States.The Society of Gynecologic Oncology COVID-19 and Gynecologic Cancer Registry was created to capture clinical courses of gynecologic oncology patients with COVID-19. Logistic regression models were employed to evaluate factors for an association with hospitalization and death, respectively, within 30 days of COVID-19 diagnosis.Data were available for 348 patients across 7 institutions. At COVID-19 diagnosis, 125 patients (36%) had active malignancy. Delay (n = 88) or discontinuation (n = 10) of treatment due to COVID-19 infection occurred in 28% with those on chemotherapy (53/88) or recently receiving surgery (32/88) most frequently delayed. In addition to age, performance status, diabetes, and specific COVID symptoms, both non-White race (adjusted odds ratio (aOR) = 3.93, 95% CI 2.06-7.50) and active malignancy (aOR = 2.34, 95% CI 1.30-4.20) were associated with an increased odds of hospitalization. Eight percent of hospitalized patients (8/101) died of COVID-19 complications and 5% (17/348) of the entire cohort died within 30 days after diagnosis.Gynecologic oncology patients diagnosed with COVID-19 are at risk for hospitalization, delay of anti-cancer treatments, and death. One in 20 gynecologic oncology patients with COVID-19 died within 30 days after diagnosis. Racial disparities exist in patient hospitalizations for COVID-19, a surrogate of disease severity. Additional studies are needed to determine long-term outcomes and the impact of race.

OBJECTIVE: Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL). METHODS: The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo. This post hoc analysis evaluated the impact of disease progression on HRQoL by comparing HRQoL at the last visit pre-progression to end of treatment (EoT), and after 4, 8, 12, and 24 weeks. Assessments included the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), the European Quality of Life Five Dimension Five Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC-QLQ-C30), and the EORTC Quality of Life Questionnaire Ovarian Cancer module (EORTC-QLQ-OV28). RESULTS: This post hoc analysis included 733 patients. Mean FOSI, EQ-5D-5L, and EQ-VAS scores deteriorated from last visit pre-progression to EoT and remained low up to 24-week follow-up. Least squares mean changes from last visit pre-progression to EoT were -2.1 (95% confidence interval -2.4, -1.7) for FOSI, -4.6 (-5.6, -3.5) for the EQ-5D-5L index, and -7.9 (-9.6, -6.3) for EQ-VAS. CONCLUSIONS: Disease progression negatively impacted HRQoL in patients with OC. PFS is clinically relevant, and prolonging PFS may preserve HRQoL. ispartof: GYNECOLOGIC ONCOLOGY vol:166 issue:3 pages:494-502 ispartof: location:United States status: published

The present article reviews the current evidence for antibody-drug conjugates (ADCs) in gynecologic cancer. ADCs consist of a highly selective monoclonal antibody for a tumor-associated antigen and a potent cytotoxic payload conjugated through a linker. Overall, the toxicity profiles of ADCs are manageable. Ocular toxicity is a known class effect of some ADCs and is managed with prophylactic corticosteroid and vasoconstrictor eye drops as well as dose interruptions/holds and dose modifications. In ovarian cancer, mirvetuximab soravtansine, an ADC targeting alpha-folate receptor (FRα), received US Food and Drug Administration (FDA) accelerated approval in November 2022 after data from the single-arm phase III SORAYA trial. A second ADC targeting FRα, STRO-002, received FDA fast track designation in August 2021. Multiple studies with upifitamab rilsodotin, an ADC comprising a NaPi2B-binding antibody, are underway. In cervical cancer, tisotumab vedotin, an ADC-targeting tissue factor, received FDA accelerated approval in September 2021 after the phase II innovaTV 204 trial. Tisotumab vedotin in combination with chemotherapy and other targeted agents is currently being evaluated. Although there are no currently approved ADCs for endometrial cancer, there are many under active evaluation, including mirvetuximab soravtansine. Trastuzumab-deruxtecan (T-DXd), an ADC targeting human epidermal growth factor receptor 2 (HER2), is currently approved for HER2-positive and HER2-low breast cancer and shows promise in endometrial cancer. Like all anticancer treatments, the decision for a patient to undergo therapy with an ADC is a personal choice that balances the potential benefits with the side effects and requires thorough and compassionate support of their physician and care team and shared decision making.

Patients with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) associated with Lynch syndrome (LS) have an increased lifetime risk of endometrial cancer (EC). Multi-gene panel testing (MGPT) is a recent hereditary cancer risk tool enabling next-generation sequencing of numerous genes in parallel. We determined the prevalence of actionable cancer predisposition gene mutations identified through MGPT in an EC patient cohort.A single center retrospective cohort study was conducted of patients with EC who had a clinical indication for genetic testing and who underwent MGPT as part of standard of care treatment between 2012 and 2021. Pathogenic mutations were identified and actionable mutations were defined as those with clinical management implications. Additionally, the number of individuals identified with LS was compared between MGPT and tumor-based screening.The study included a total of 224 patients. Thirty-three patients [14.7%, 95% confidence interval (CI) = 10.4-20.1] had actionable mutations. Twenty-one patients (9.4%, 95% CI = 5.9-14.0) had mutations in LS genes (4 MLH1, 5 MSH2, 7 MSH6, 4 PMS2, 1 Epcam-MSH2). MGPT revealed two patients with LS (9.5% of LS cases) not identified through routine tumor-based screening. Thirteen patients (5.8%, 95% CI = 3.1-9.7) had at least one actionable mutation in a non-Lynch syndrome gene (6 CHEK2, 2 BRCA2, 2 ATM, 2 APC, 1 RAD51C, 1 BRCA1).Germline MGPT is both feasible and informative as it identifies LS cases not found on tumor testing as well as additional actionable mutations in patients with EC.

The emergence of clinical trial data for poly(ADP-ribose) polymerase inhibitors (PARPi), in BRCA-associated ovarian cancer (epithelial ovarian cancer [EOC]) in 2009 (Lancet 2010;376:245-251) unleashed a rapid series of additional asset development and clinical trial activation across all lines of EOC treatment, ultimately leading to 8 new approvals of 3 different PARPi in EOC since 2014. Monotherapy iPARPi were approved as frontline maintenance treatment for all patients with EOC who respond to platinum-based chemotherapy irrespective of biomarker (niraparib) and for BRCA-associated cancers (olaparib) (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1; https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf). Combination of olaparib and bevacizumab was approved as maintenance for patients in response to platinum-based and bevacizumab containing frontline therapy whose tumor is characterized as homologous recombination deficient and as approved test by the Food and Drug Administration, inclusive of BRCA-associated cancers (N Engl J Med 2019;381:2416-2428). Niraparib, olaparib, and rucaparib were also approved as maintenance treatment following response to platinum-based therapy in the recurrent setting irrespective of biomarker (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1; https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf). All 3 PARPi were also approved as treatment in lieu of chemotherapy for patients with BRCA-associated cancers in third line and beyond (https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1;https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf) and platinum-sensitive homologous recombination deficient in the fourth line and beyond (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf), as well as the National Comprehensive Cancer Network listed in combination with bevacizumab for treatment of patients with platinum-sensitive recurrent disease (https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf). Ongoing clinical trials in all lines of treatment are evaluating combinations of therapies to improve efficacy among biomarker negative tumors as well as overcome acquired PARPi resistance due to prior use.

The objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)'s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer.This was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p0.05.Of 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09-8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05-0.23).Most patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

The GOG Foundation, Inc. (GOG-F) is a non-profit 501(c)(3) organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. GOG Partners (GOG-P) is a program of the GOG-F and is positioned alongside NRG Oncology under the GOG-F organizational umbrella. GOG-P operates outside of the federally funded NCI NRG Oncology, a key distinguishing feature. By functioning as a site management organization (SMO), GOG-P provides an additional platform for clinical trial development, mentorship opportunities, patient accrual, and site infrastructure support yielding an expanded gynecologic oncology clinical trials infrastructure in the US. GOG-P has a consistent track record of conducting high quality clinical trials that lead to bringing novel FDA approved treatments for gynecologic cancer. This manuscript summarizes the history and organizational structure of the GOG-P. In addition, we outline the other key supportive programs within the GOG-F that help support the GOG-P effort to perform transformative gynecologic cancer research.

Background: Lynch syndrome accounts for 3% of newly diagnosed endometrial cancers and colon cancers. Identifying patients with Lynch syndrome is fundamental to enable proper screening and prevention of at-risk malignancies, along with encouraging cascade testing of family members. We aimed to assess medical students' knowledge of Lynch syndrome-associated cancers and screening and prevention measures to decrease malignancy risk in patients with Lynch syndrome. Methods: An anonymous, voluntary, multiple-choice survey was emailed to 14 medical schools throughout the US to evaluate medical students’ knowledge of Lynch syndrome. Results: We surveyed 342 medical students, and 65% were third or fourth-year medical students. Ninety-three percent knew that colon cancer is one of two most commonly diagnosed cancers in Lynch syndrome; however, only 37% knew endometrial cancer was the other most common malignancy in Lynch syndrome patients. Fifty-nine percent of students recognized that 2-5% of all newly diagnosed endometrial and colon cancers are due to Lynch syndrome. Ninety-one percent recognized a family history that would indicate evaluation for Lynch syndrome, but only 49% knew that all patients diagnosed with endometrial cancer prior to age 50 should be evaluated for Lynch syndrome as per the National Comprehensive Cancer Network guidelines regardless of other risk factors. Conclusion: Almost two-thirds of medical students did not recognize endometrial cancer as a common Lynch syndrome malignancy and less than 50% were aware of when to evaluate patients with endometrial cancer for Lynch syndrome; comparatively almost all students recognized the link between colon cancer and Lynch syndrome. Curriculum change with targeted education regarding endometrial cancer and Lynch syndrome during medical school obstetrics and gynecology clinical rotations should be implemented. This call to action is critical in improving the diagnosis of Lynch syndrome, evaluation, screening, and prevention of cancers in both patients and family members to reduce mortality.

In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. This manuscript, Part II in a two-part series, includes specific recommendations on treatment of recurrent disease, post treatment surveillance and survivorship, considerations for younger women, and special situations. Part I covered histopathology and molecular pathology, risk factors, presentation and diagnostic approach, surgical approach and adjuvant therapy.

In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. Despite these advances, the incidence of endometrial cancer as well as the deaths attributable to the disease have continued to rise; from 1987 to 2014 there has been a 75% increase in cases and almost 300% increase in endometrial cancer deaths. Fortunately, since then, there has been progress in the treatment of patients with endometrial cancer with increased utilization of molecular pathology, greater understanding of genetic predisposition, enhanced methods for lymph node assessment, a broader understanding of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship and surveillance. The purpose of this document is to present a comprehensive review of this progress.The authors reviewed the available evidence, contributed to the development of this manuscript, provided critical review of the guidelines, and finalized the manuscript recommendations. The review was also presented to and approved by the Society of Gynecologic Oncology (SGO) Clinical Practice Committee, SGO Publications Committee, and the SGO board members prior to submission for publication. The recommendations for this manuscript were developed by a panel of gynecologic oncologists who were members of the SGO Clinical Practice and Education Committees. Panelists reviewed and considered evidence from current uterine cancer literature. The terminology used in these guidelines was adopted from the ASCCP management guidelines [1] using a two-part rating system to grade the strength of recommendation and quality of evidence (Table 1). The rating for each recommendation is given in parentheses.

OBJECTIVE To implement a quality-improvement intervention aimed at reducing unnecessary opioid prescriptions for patients who are undergoing gynecologic surgery. METHODS This was a retrospective cohort study that included data from the pre- and post-quality-improvement initiative cohorts. Patients at an urban, tertiary academic medical center who were undergoing scheduled minimally invasive surgery and open abdominal surgery by a gynecologic oncologist were included. Patients underwent preoperative counseling, standardization of perioperative analgesia, and a postoperative opioid prescribing algorithm. Descriptive statistics were calculated for demographic and perioperative characteristics, process measures, and outcome measures. RESULTS A total of 532 abdominal surgeries were analyzed. The total percentage of patients discharged with an opioid prescription decreased from 82.7% (n=229/276) to 23.1% (n=59/256) (P

Gynecologic oncologists have the unique opportunity of caring for patients in a broad range of surgical and medical settings. With increasing awareness of the opioid epidemic and the various factors that contribute to chronic opioid use, gynecologic oncologists must also better understand how to best address acute postoperative pain without unknowingly placing patients at risk for opioid misuse. This article examines the use of opioids in the acute surgical setting and provides clinical guidelines and various strategies to reduce opioid misuse.

Background Timely genetic testing at ovarian cancer diagnosis is essential as results impact front line treatment decisions. Our objective was to determine rates of genetic counseling and testing with an expedited genetics referral pathway wherein women with newly-diagnosed ovarian cancer are contacted by a genetics navigator to facilitate genetic counseling. Methods Patients were referred for genetic counseling by their gynecologic oncologist, contacted by a genetics navigator and offered appointments for genetic counseling. Patients completed quality of life (QoL) surveys immediately pre- and post-genetic assessment and 6 months later. The primary outcome was feasibility of this pathway defined by presentation for genetic counseling. Results From 2015 to 2018, 100 patients were enrolled. Seventy-eight had genetic counseling and 73 testing. Median time from diagnosis to genetic counseling was 34 days (range 10–189). Among patients who underwent testing, 12 (16%) had pathogenic germline mutations (BRCA1-7, BRCA2-4, MSH2-1). Sixty-five patients completed QoL assessments demonstrating stress and anxiety at time of testing, however, scores improved at 6 months. Despite the pathway leveling financial and logistical barriers, patients receiving care at a public hospital were less likely to present for genetic counseling compared to private hospital patients (56% versus 84%, P = 0.021). Conclusions Facilitated referral to genetic counselors at time of ovarian cancer diagnosis is effective, resulting in high uptake of genetic counseling and testing, and does not demonstrate a long term psychologic toll. Concern about causing additional emotional distress should not deter clinicians from early genetics referral as genetic testing can yield important prognostic and therapeutic information.