Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma: NRG Oncology/GOG Study 279.

PURPOSE: To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. METHODS: Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. RESULTS: Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. CONCLUSION: Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Impact of steroid use and glycemic control on postoperative complications in diabetic gynecologic oncology patients undergoing laparotomy.

Objective: We aimed to assess the impact of preoperative steroid administration and perioperative glycemic control on postoperative complications in diabetic gynecologic oncology patients undergoing laparotomy. Methods: This retrospective cohort study included gynecologic oncology patients with Type I and Type II diabetes (DM) undergoing laparotomy for any gynecologic indication at a single academic center from 10/2017 to 09/2020. The primary outcome was the rate of postoperative complications. Preoperative steroid administration and 24-hour postoperative average serum blood glucose (BG) ≥ 180 mg/dL were the studied exposures. Data was analyzed with SPSS Statistics v.28. Results: 225 patients met inclusion criteria; 47.6 % had postoperative complications. Patient demographics were similar between patients with and without postoperative complications. Patients with complications had higher BMIs (36.8 vs. 34.0; p = 0.03), bowel surgery (33.0 % vs. 17.1 %; p = 0.008), operative time ≥ 240 min (14.2 % vs. 5.1 %; p = 0.02) and average BG ≥ 180 (63.6 % vs. 40.2 %; p < 0.01). On multivariate analysis, bowel surgery (OR 2.4 (1.2-4.8); p = 0.01) and average BG ≥ 180 (OR 2.8 (1.6-4.9); p < 0.01) remained significant predictors of postoperative complications. There were no differences in complication rates (42.3 % vs. 42.6 %; p = 1.0) between patients who received preoperative steroids and those who did not. When stratified by average postoperative BG < 180 mg/dL vs. BG ≥ 180 mg/dL, there was no difference in Clavien-Dindo classification, 30-day readmission rate (28.2 % vs. 22.1 %; p = 0.49) or 30-day mortality rate (2.9 % vs. 0.0 %; p = 0.53). Conclusion: The administration of preoperative steroids did not increase complication rates. Perioperative hyperglycemia was associated with an increased risk of postoperative complications. Optimizing perioperative glycemic control is imperative to decrease postoperative complications.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.

Experiences of Family Communication and Cascade Genetic Testing for Hereditary Cancer in Medically Underserved Populations-A Qualitative Study.

We sought to explore the intrafamilial communication and cascade genetic testing (CGT) experiences of patients with hereditary cancer from diverse, medically underserved populations and their relatives. Participants included patients receiving oncology care at an urban, safety net hospital in Texas or comprehensive cancer center in Alabama and their first-degree relatives. In-depth semi-structured qualitative interviews were completed wherein patients shared their experiences with genetic counseling (GC), genetic testing (GT), and communicating their results to relatives. Relatives shared their experiences receiving information from the patient and considering CGT. Interviews were transcribed, coded, and themes were identified. Of 25 participating patients, most recalled key aspects of GC and their GT results. Most (80%) patients shared their results with relatives, but only some relatives underwent CGT; patients reported low perceived susceptibility to hereditary cancer as a common barrier to CGT for their relatives. Of 16 participating relatives, most reported feeling distress upon learning the patient's GT results. Relatives were fearful of learning their own CGT results but identified prevention and early detection as CGT benefits. Interviews identified opportunities during family communication to improve relatives' perceived susceptibility to hereditary cancer. Tailored resources may support patients and relatives experiencing distress and fear during GT. PREVENTION RELEVANCE: This study of intrafamilial communication and cascade genetic testing experiences of patients with hereditary cancer and their relatives from diverse, medically underserved populations identified relatives' perceived susceptibility to hereditary cancer risks, distress, and fear as frequent reactions and barriers to testing. These results may inform future hereditary cancer prevention efforts.

New Paradigms in the Treatment of Cervical Cancer.

Despite effective screening strategies and the development and implementation of prophylactic high-risk human papillomavirus vaccination, cervical cancer remains a significant public health burden. This burden is most pronounced in under-resourced countries without fully developed screening and vaccination programs, although the disease remains present worldwide, including in industrialized countries. To that end, the World Health Organization (WHO) has an active focus on the elimination of cervical cancer, with objective metrics to be achieved by countries by the year 2030. Although increased vaccination and screening will be needed to approach potential eradication of cervical cancer, as recognized by the WHO initiative, treatment will need to continue to not only be effective in the near term, but to improve outcomes as well. Accordingly, assessments to improve primary treatment options, including surgery for women with early-stage disease, modification of chemoradiation for those with locally advanced cervical cancer, and systemic therapy for those with recurrent or metastatic presentations, are ongoing. Accordingly, we highlight important areas of both recent and ongoing focus as they relate to improving cervical cancer outcomes.

Use of a mobile health patient engagement technology improves perioperative outcomes in gynecologic oncology patients.

OBJECTIVE: To evaluate the impact of a mobile health patient engagement technology (PET) on postoperative outcomes in gynecologic oncology patients. METHODS: All gynecologic oncology patients undergoing laparotomy on an enhanced recovery program (ERP) were approached from July 2019 to May 2021 to enroll in a PET, which can be accessed by computer, tablet, or smart phone. This platform provides enhanced pre- and postoperative patient education and remote patient monitoring. Patients who elected to participate were provided with targeted education based on their age and comorbidities and were asked to complete daily health checks during the postoperative period. Participants in the PET were compared to patients who opted out as well as to a historical cohort from prior to PET implementation. Patient and procedure-level factors were recorded. The primary outcomes were length of stay (LOS) and 30-day readmission rate. Analysis was performed using SPSS v.26. RESULTS: 682 women met inclusion criteria during the study time; 347 in the PET group and 335 in the control group. Demographic and other factors including race, BMI (kg/m2), Charlson Comorbidity Index (CCI), surgical complexity, and insurance status were not different between the PET and control group; however, patients in the PET cohort were slightly younger (55.0 yo vs. 57.2 yo; p = 0.04). Patients in the PET group had a significantly shorter LOS (2.9 days vs. 3.6 days; p < 0.01) and lower readmission rate (4.3% vs. 8.6%; p < 0.01) when compared with the control group. CONCLUSIONS: Use of a PET in our gynecologic oncology patients decreased LOS by nearly one day despite an absence of differences in other demographic and surgical factors other than age. Furthermore, there was a 50% reduction in readmission rates in the PET group. The use of a PET allows for healthcare professionals to engage, evaluate, and treat patients in a way that improves perioperative care.

Assessing Geographic Variation in Rates of Cervical Cancer and Recurrent or Metastatic Cervical Cancer Among Medicaid Enrollees.

OBJECTIVE: The objective of this study was to evaluate trends in prevalence of cervical cancer (CC) and rates of recurrent or metastatic cervical cancer (r/mCC) treatment initiation at the state and metropolitan statistical area (MSA) levels among Medicaid enrolled females from 2016 to 2019. METHODS: Retrospective analyses of nationwide Medicaid claims data were used to identify adult CC and r/mCC patients from 2016 to 2019. CC prevalence was estimated as the proportion of females diagnosed with CC out of all adult female Medicaid beneficiaries, and r/mCC by the proportion of CC patients who initiated a systemic treatment not associated with surgery or radiation to the number of enrollees with CC diagnosis in each state or MSA. Overall and annual rates were calculated for each state and MSA from 2016 to 2019. RESULTS: The analytic cohort included 70,865 adult female Medicaid beneficiaries with CC from 2016 to 2019, among whom 3375 were identified as r/mCC patients. Nationwide annual prevalence of CC remained relatively stable from 2016 to 2019, while r/mCC decreased slightly over the study period. Several MSAs experienced increasing rates of r/mCC from 2016 to 2019, including Mayaguez, PR, Aguadeilla-Isabela, PR, and Green Bay, WI. CONCLUSIONS: Claims data demonstrate areas in the United States with disproportionately high or increasing CC or r/mCC burden, indicating a potential gap in preventative care for females and an unmet need for education and health care resource allocation. Future research should evaluate associations between community-level factors and r/mCC burden.

Pertuzumab Plus Trastuzumab in Patients With Endometrial Cancer With ERBB2/3 Amplification, Overexpression, or Mutation: Results From the TAPUR Study.

PURPOSE: The TAPUR Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with endometrial cancer (EC) with ERBB2 or ERBB3 (ERBB2/3) amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab (P + T) are reported. METHODS: Eligible patients had advanced EC, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2/3 amplification, overexpression, or mutation. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks (SD16+) duration. Secondary end points include safety, duration of response, duration of SD, progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-eight patients were enrolled from March 2017 to November 2019; all patients were evaluable for efficacy and toxicity. Seventeen patients had tumors with ERBB2/3 amplification and/or overexpression, eight with both ERBB2 amplification and ERBB2/3 mutations, and three with only ERBB2 mutations. Ten patients had DC (two partial response and eight SD16+); all 10 had ERBB2 amplification, and 6 of the 10 patients with DC had >1 ERBB2/3 alteration. DC and OR rates were 37% (95% CI, 21 to 50) and 7% (95% CI, 1 to 24), respectively; the median PFS and median OS were 16 weeks (95% CI, 10-28) and 61 weeks (95% CI, 24-105), respectively. One patient experienced a grade 3 serious adverse event (muscle weakness) at least possibly related to P + T. CONCLUSION: P + T has antitumor activity in heavily pretreated patients with EC with ERBB2 amplification and warrants additional study.

Patterns of care and health care resource use among Medicaid-enrolled women with recurrent or metastatic cervical cancer.

BACKGROUND: Cervical cancer is a public health challenge and remains a disease with high unmet need. Previous real-world studies demonstrated significant variability in treatments for patients with recurrent or metastatic cervical cancer (r/mCC). A large proportion of patients with cervical cancer are insured through Medicaid; however, previous studies examining treatment patterns for r/mCC have not included Medicaid patients. As the r/mCC treatment landscape continues to evolve, there is a need to understand current real-world unmet need among patients with r/mCC enrolled in Medicaid. OBJECTIVE: To evaluate treatment patterns and health care resource utilization (HCRU) among Medicaid-enrolled women with r/mCC. METHODS: This is a retrospective analysis of nationwide Medicaid claims to assess patient characteristics, treatment patterns, and HCRU among patients with r/mCC between 2016 and 2019. First-line treatment (1L) for r/mCC was defined by the first administration of systemic therapy without concomitant radiation or surgery. Patient characteristics, treatment patterns, and HCRU were characterized by line of therapy. RESULTS: A total of 3,375 eligible adult female patients initiated systemic treatment for r/mCC between 2016 and 2019. Mean age at treatment initiation was 52.9 (SD ± 12.8) years. Nearly 1,300 (1,294, 38.3%) women had evidence of receiving second-line treatment (2L), with nearly one-third (N = 420) of those also having evidence of third-line treatment. The majority (60.5%) of 1L regimens were doublet chemotherapy ± bevacizumab, consistent with treatment guidelines. In contrast, no clear preferred treatment choice was observed among patients receiving 2L or later (2L+) therapy. Notably, immunotherapy accounted for 21.6% of treatment regimens in 2L/3L overall, with its use increasing substantially over time (<6% in 2016 to 40.8% in 2019). Despite increased use of immunotherapy, however, most patients did not remain on treatment for prolonged durations (immunotherapy median duration 2.2 months vs 2.4 months for nonimmunotherapy; P = 0.5). Across most HCRU measures (inpatient admissions, outpatient visits, emergency department visits, and pharmacy claims), 2L+ patients had significantly less utilization per patient compared with 1L patients in unadjusted analyses. CONCLUSIONS: This analysis found that the majority of Medicaid patients with r/mCC received guideline-recommended standard of care in 1L between 2016 and 2019. However, there was no clear standard of care for patients with 2L+ r/mCC enrolled in Medicaid over this time period. Although immunotherapy use is increasing, short durations of treatment suggest a potential unmet medical need among this population. New therapies should provide meaningful clinical benefit without significant increase in HCRU for Medicaid enrollees needing treatment for r/mCC. DISCLOSURES: Dr Leath has received consulting fees from Seagen Inc. for service on Scientific Advisory Boards, cervical cancer research funding from Agenus, Rubius Therapeutics, and Seagen Inc., and funding from the NCI UG1 CA23330 and P50 CA098252. Dr Ting and Dr Zhang are employees and stock owners of Seagen Inc. Mr Fiori and Dr Pauly are current employees and Ms Nysenbaum is a former employee of Manatt Health Strategies, which received funding from Seagen Inc. to conduct the study described here. Manatt Health Strategies has also previously received consulting fees from other pharmaceutical companies that they are not permitted to publicly disclose. This research was funded by Seagen Inc. Seagen Inc. conceptualized the study approach, methodology, and contributed to article writing and review but was not involved in data acquisition, manipulation, or analysis.

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).

Historic Clinical Trial External Control Arm Provides Actionable GEN-1 Efficacy Estimate Before a Randomized Trial.

PURPOSE: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients' end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy. METHODS: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to create an external control arm (ECA). RESULTS: Fifteen OVATION-1 patients (15 of 18, 83%) were matched to 15 (37%, 15 of 41) Medidata historical trial control patients. Matching attenuated preexisting differences in attributes between the groups. The median progression-free survival time was not reached by the OVATION-1 group and was 15.8 months (interquartile range, 11.40 months to nonestimable) for the ECA. The hazard of progression was 0.53 (95% CI, 0.16 to 1.73), favoring GEN-1 patients. Compared with ECA patients, OVATION-1 patients had more nausea, fatigue, chills, and infusion-related reactions. CONCLUSION: Comparing results of a single-arm early-phase trial to those of a rigorously matched HCT ECA yielded insights regarding comparative efficacy prior to a randomized controlled trial. The effect size estimate itself informed both the decision to continue development and the randomized phase II trial (ClinicalTrials.gov identifier: NCT03393884) sample size. The work illustrates the potential of HCT data to inform drug development.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

The MEMORY Study: MulticentEr study of Minimally invasive surgery versus Open Radical hYsterectomy in the management of early-stage cervical cancer: Survival outcomes.

OBJECTIVE: The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. METHODS: This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007-12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. RESULTS: We identified 1093 cases for analysis-715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03-149.51) and 54.98 months (range, 0.03-145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9-90.4%) and 89% (95% CI: 84.9-92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47-1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6-97.2%) and 96.6% (95% CI: 93.8-98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43-1.52; P = 0.5). CONCLUSION: This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.

Feasibility, Safety, and Provider Perspectives of Bipolar Electrosurgical Cautery Device for (Opportunistic or Complete) Salpingectomy at the Time of Cesarean Delivery.

OBJECTIVES: The aim of the study is to evaluate the use of a bipolar electrocautery device for complete salpingectomy at cesarean to improve procedure completion rates, operative time, and surgeon reported satisfaction as compared with standard bilateral tubal ligation (BTL) and suture-cut-tie salpingectomy. STUDY DESIGN: This is a prospective cohort study of women undergoing planned, non-emergent cesarean with desired sterilization with complete salpingectomy utilizing a bipolar electrocautery device. Study patients were compared with historic controls from a randomized controlled trial (RCT) of complete salpingectomy via suture-cut-tie method versus BTL conducted at our institution (SCORE trial, NCT02374827). Outcomes were compared with groups from the original RCT. RESULTS: Thirty-nine women were consecutively enrolled (12/2018-11/2019) into the device arm of the study and compared with the original SCORE cohort (n = 40 BTL, n = 40 salpingectomy without a device). Salpingectomy performance with the bipolar electrocautery device was successfully completed in 100% (39/39) of enrolled women, with one device failure requiring the use of a second device, as compared with 95% (38/40) in the BTL (p = 0.49) and 67.5% (27/40) in salpingectomies without a device (p < 0.001). Mean operative time of sterilization procedure alone demonstrated device use as having the shortest operative time of all (device salpingectomy 5.0 ± 3.6 vs. no device 18.5 ± 8.3 minutes, p < 0.001; and vs. BTL 6.9 ± 5.0, p = 0.032). Mean sterilization procedure endoscopic band ligation (EBL) was demonstrated to be significantly different between each group, least amongst BTL followed by device (6.3 ± 4.8 vs. 8.4 ± 24.8, p < 0.001), and most by suture-cut-tie method (17.7 ± 14.3, p < 0.001 compared with device). Surgeon reported attitudes of complete salpingectomy performance in general practice outside an academic setting was greater with a device than without (79.5 vs. 35.3%; p < 0.001). CONCLUSION: Use of a bipolar electrocautery device improved operative times and surgeon satisfaction for salpingectomy at cesarean over standard suture ligation. Device use improved surgeon reported outcomes and may improve incorporation of complete salpingectomy at cesarean. KEY POINTS: · Electrocautery bipolar device use was safe at the time of salpingectomy during cesarean.. · Greater surgeon satisfaction occurs using a device than without.. · Decreased surgical time with device use is seen making the procedure equal to BTL..

Cervical cancer - times they are a changing: A report from the Society of Gynecologic Oncology journal club.

In January 2021, the Society of Gynecologic Oncology (SGO) Clinical Practice and Education Committees launched a "Journal Club" webinar series to invite national experts to discuss literature pertaining to common clinical scenarios encountered by the members of SGO. On December 13, 2021, SGO hosted its third journal club focused on the use of immunotherapy in cervical cancer. Charles A. Leath, III from the O'Neal Comprehensive Cancer at the University of Alabama and Leslie M. Randall from Massey Cancer Center at Virginia Commonwealth University discussed the recently published KEYNOTE-826 trial (Colombo et al., 2021) and Jyoti Mayadev from the University of California, San Diego Moores Cancer Center discussed GOG-9929 (Mayadev et al., 2020). Renata Urban from the University of Washington and Christine S. Walsh from the University of Colorado served as moderators. The following is a report of the journal club presentation.

Barriers and facilitators affecting presentation in women with early versus advanced stage cervical cancer.

Background: This study was performed to evaluate the barriers and facilitators associated with patient presentation for early stage (ES) versus advanced stage (AS) cervical cancer (CC). Methods: A mixed-method approach was used to collect quantitative (i.e., demographics and medical/screening histories) and qualitative data (individual interviews assessing patients' perceptions regarding their general health, HPV and CC screening, and barriers and facilitators to CC care). Two separate investigators coded the interviews for major themes that occurred with an agreement that 50% or more of the themes would be included. Results: Twenty-five women agreed to participate in the study with 80% completing the interview. Patients with ES disease were classified as Stage IA1-Stage IB3; patients with Stage IIA-IVB disease were classified with AS disease. Frequent barriers in the ES group were lack of knowledge, competing priorities, feeling healthy, lack of time or health insurance, and being embarrassed/uncomfortable. Frequent barriers in the AS group were lack of knowledge, competing priorities, avoidance/procrastination, fear of the healthcare system or finding something wrong, and lack of perceived risk to CC. Facilitators for ES included understanding the importance of the Pap test, having an abnormal Pap test, and knowing someone with CC. Having abnormal symptoms was the only facilitator for AS patients. Conclusions: Structural and intrapersonal barriers to CC care persist but differ between ES and AS patients. Multi-level interventions are needed to address the wide array of issues that women highlighted in this study including potential innovative methods to increase access to care and engagement with the healthcare system.

Development of Delivery Systems for Local Administration of Cytokines/Cytokine Gene-Directed Therapeutics: Modern Oncologic Implications.

PURPOSE OF REVIEW: In this review, we discuss modern cytokine delivery systems in oncologic care, focusing on modalities being developed in the clinical trials or currently in use. These include pegylation, immune-cytokine drug conjugates, cytokine-expressing plasmid nanoparticles, nonviral cytokine nanoparticles, viral systems, and AcTakines. RECENT FINDINGS: Cytokine therapy has the potential to contribute to cancer treatment options by modulating the immune system towards an improved antitumor response and has shown promise both independently and in combination with other immunotherapy agents. Despite promising preliminary studies, systemic toxicities and challenges with administration have limited the impact of unmodified cytokine therapy. In the last decade, novel delivery systems have been developed to address these challenges and facilitate cytokine-based oncologic treatments. Novel delivery systems provide potential solutions to decrease dose-limiting side effects, facilitate administration, and increase the therapeutic activity of cytokine treatments in oncology care. The expanding clinical and translational research in these systems provides an opportunity to augment the armamentarium of immune oncology and may represent the next frontier of cytokine-based immuno-oncology.