ARTISTRY-7: phase III trial of nemvaleukin alfa plus pembrolizumab vs chemotherapy for platinum-resistant ovarian cancer.

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6-20% and progression-free survival of ≈3-4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).

In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join.

Human papillomavirus vaccination receipt and provider counseling rates among high-risk patients.

OBJECTIVE: We describe provider documented counseling patterns and perception regarding HPV vaccination among patients with a history of cervical dysplasia. METHODS: All patients ages 21-45 who underwent colposcopy at a single academic medical center from 2018 to 2020were sent a self-administered survey through the electronic medical record patient portal to assess their attitudes regarding human papillomavirus (HPV) vaccination. Demographic information, HPV vaccination history, and documented obstetrics and gynecology provider counseling at the time of colposcopy were examined. RESULTS: Of 1465patients, 434 (29.6 %) reported or had documented receipt of at least one dose of the human papillomavirus vaccine. The remainder reported they were not vaccinated or had no documentation of vaccination. Proportion of vaccinated patients was higher among White compared to Black and Asian patients (P = 0.02). On multivariate analysis, private insurance (aOR 2.2, 95 % CI 1.4-3.7) was associated with vaccinated status while Asian race (aOR 0.4, 95 % CI 0.2-0.7) and hypertension (aOR 0.2, 95 % CI 0.08-0.7) were less likely to be associated with vaccination status. Among patients with unvaccinated or unknown vaccination status, 112 (10.8 %) received documented counseling regardingcatch-up human papillomavirus vaccination at a gynecologic visit. Patients seen by a sub-specialist obstetrics and gynecologic provider were more likely to have documented provider counseling regarding vaccination compared to those seen by a generalist obstetric/gynecologist provider (26 % vs 9.8 %, p < 0.001). Patients cited lack of physician discussion (53.7 %) and the belief that they were too old to receive the HPV vaccine (48.8 %) as the main reasons for remaining unvaccinated. CONCLUSION: HPV vaccination and the rate of obstetric and gynecologic provider counseling regarding HPV vaccination among patients undergoing colposcopy remains low. When surveyed, many patients with a history of colposcopy cited provider recommendation as afactor in their decision to undergo adjuvant HPV vaccination, demonstrating the importance of provider counseling in thisgroup.

Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms.

BACKGROUND: Most endometrial cancer cases are preceded by abnormal uterine bleeding, offering a potential opportunity for early detection and cure of endometrial cancer. Although clinical guidelines exist for diagnostic workup of abnormal uterine bleeding, consensus is lacking regarding optimal management for women with abnormal bleeding to diagnose endometrial cancer. OBJECTIVE: We report the baseline data from a prospective clinical cohort study of women referred for endometrial evaluation at the Mayo Clinic, designed to evaluate risk stratification in women at increased risk for endometrial cancer. Here, we introduce a risk-based approach to evaluate diagnostic tests and clinical management algorithms in a population of women with abnormal bleeding undergoing endometrial evaluation at the Mayo Clinic. STUDY DESIGN: A total of 1163 women aged ≥45 years were enrolled from February 2013 to May 2019. We evaluated baseline absolute risks and 95% confidence intervals of endometrial cancer and endometrial intraepithelial neoplasia according to clinical algorithms for diagnostic workup of women with postmenopausal bleeding (assessment of initial vs recurrent bleeding episode and endometrial thickness measured through transvaginal ultrasound). We also evaluated risks among women with postmenopausal bleeding according to baseline age (<60 vs 60+ years) as an alternative example. For this approach, biopsy would be conducted for all women aged 60+ years and those aged <60 years with an endometrial thickness of >4 mm. We assessed the clinical efficiency of each strategy by estimating the percentage of women who would be referred for endometrial biopsy, the percentage of cases detected and missed, and the ratio of biopsies per case detected. RESULTS: Among the 593 women with postmenopausal bleeding, 18 (3.0%) had endometrial intraepithelial neoplasia, and 47 (7.9%) had endometrial cancer, and among the 570 premenopausal women with abnormal bleeding, 8 (1.4%) had endometrial intraepithelial neoplasia, and 7 (1.2%) had endometrial cancer. Maximum risk was noted in women aged 60+ years (17.7%; 13.0%-22.3%), followed by those with recurrent bleeding (14.7%; 11.0%-18.3%). Among women with an initial bleeding episode for whom transvaginal ultrasound was recommended, endometrial thickness did not provide meaningful risk stratification: risks of endometrial cancer and endometrial intraepithelial neoplasia were nearly identical in women with an endometrial thickness of >4 mm (5.8%; 1.3%-10.3%) and ≤4 mm (3.6%; 0.9%-8.6%). In contrast, among those aged <60 years with an endometrial thickness of >4 mm, the risk of endometrial cancer and endometrial intraepithelial neoplasia was 8.4% (4.3%-12.5%), and in those with an endometrial thickness of ≤4 mm, the risk was 0% (0.0%-3.0%; P=.01). The most efficient strategy was to perform biopsy in all women aged 60+ years and among those aged <60 years with an endometrial thickness of >4 mm, with the lowest percentage referred to biopsy while still detecting all cases. CONCLUSION: Existing clinical recommendations for endometrial cancer detection in women with abnormal bleeding are not consistent with the underlying risk. Endometrial cancer risk factors such as age can provide important risk stratification compared with the assessment of recurrent bleeding. Future research will include a formal assessment of clinical and epidemiologic risk prediction models in our study population as well as validation of our findings in other populations.

A prospective clinical cohort study of women at increased risk for endometrial cancer.

OBJECTIVE: To evaluate endometrial cancer (EC) risk assessment and early detection strategies in high-risk populations, we designed a large, prospective cohort study of women undergoing endometrial evaluation to assess risk factors and collect novel biospecimens for future testing of emerging EC biomarkers. Here we report on the baseline findings of this study. METHODS: Women aged ≥45 years were enrolled at the Mayo Clinic from February 2013-June 2018. Risk factors included age, body mass index (BMI), smoking, oral contraceptive and hormone therapy use, and parity. We collected vaginal tampons, endometrial biopsies, and Tao brush samples. We estimated mutually-adjusted odds ratios (OR) and 95% confidence intervals (CI) using multinomial logistic regression; outcomes included EC, atypical hyperplasia, hyperplasia without atypia, disordered proliferative endometrium, and polyps, versus normal endometrium. RESULTS: Subjects included 1205 women with a mean age of 55 years; 55% were postmenopausal, and 90% had abnormal uterine bleeding. The prevalence of EC was 4.1% (n = 49), predominantly diagnosed in postmenopausal women (85.7%). Tampons and Tao brushings were obtained from 99% and 68% of women, respectively. Age (OR 1.14, 95% CI 1.1-1.2) and BMI (OR 1.39, 95% CI 1.1-1.7) were positively associated with EC; atypical hyperplasia (OR 1.07, 95% CI 1.0-1.1; OR 2.00, 95% CI 1.5-2.6, respectively), and polyps (OR 1.06, 95% CI 1.0-1.1; OR 1.17, 95% CI 1.0-1.3, respectively); hormone therapy use and smoking were inversely associated with EC (OR 0.42, 95%, 0.2-0.9; OR 0.43, 95% CI, 0.2-0.9, respectively). Parity and past oral contraception use were not associated with EC. CONCLUSIONS: Well-established EC risk factors may have less discriminatory accuracy in high-risk populations. Future analyses will integrate risk factor assessment with biomarker testing for EC detection.

Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis.

Importance: As the worldwide burden of endometrial cancer continues to rise, interest is growing in the evaluation of early detection and prevention strategies among women at increased risk. Focusing efforts on women with postmenopausal bleeding (PMB), a common symptom of endometrial cancer, may be a useful strategy; however, PMB is not specific for endometrial cancer and is often caused by benign conditions. Objective: To provide a reference of the prevalence of PMB in endometrial cancers and the risk of endometrial cancer in women with PMB. Data Sources: For this systematic review and meta-analysis, PubMed and Embase were searched for English-language studies published January 1, 1977, through January 31, 2017. Study Selection: Observational studies reporting the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB in unselected populations were selected. Data Extraction and Synthesis: Two independent reviewers evaluated study quality and risk of bias using items from the Newcastle-Ottawa Quality Assessment Scale and the Quality Assessment of Diagnostic Accuracy Studies tool. Studies that included highly selected populations, lacked detailed inclusion criteria, and/or included 25 or fewer women were excluded. Main Outcomes and Measures: The pooled prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB. Results: A total of 129 unique studies, including 34 432 unique patients with PMB and 6358 with endometrial cancer (40 790 women), were analyzed. The pooled prevalence of PMB among women with endometrial cancer was 91% (95% CI, 87%-93%), irrespective of tumor stage. The pooled risk of endometrial cancer among women with PMB was 9% (95% CI, 8%-11%), with estimates varying by use of hormone therapy (range, 7% [95% CI, 6%-9%] to 12% [95% CI, 9%-15%]; P < .001 for heterogeneity) and geographic region (range, 5% [95% CI, 3%-11%] in North America to 13% [95% CI, 9%-19%] in Western Europe; P = .09 for heterogeneity). Conclusions and Relevance: Early detection strategies focused on women with PMB have the potential to capture as many as 90% of endometrial cancers; however, most women with PMB will not be diagnosed with endometrial cancer. These results can aid in the assessment of the potential clinical value of new early detection markers and clinical management strategies for endometrial cancer and will help to inform clinical and epidemiologic risk prediction models to support decision making.

Evidence-Based Screening Recommendations for Occult Cancers in the Setting of Newly Diagnosed Extramammary Paget Disease.

OBJECTIVES: To identify the rates of associated and occult cancers in patients with extramammary Paget disease (EMPD) discovered using cancer screening methods at a tertiary medical center; to propose evidence-based cancer screening guidelines at the time of diagnosis of EMPD; and to clarify terminology associating EMPD with underlying malignancies. PATIENTS AND METHODS: A retrospective review of patients with histologically confirmed EMPD presenting for care at our institution between January 1, 1992, and December 31, 2015, was performed. Both male and female patients were included. Descriptive analysis was performed. RESULTS: A total of 161 patients met the inclusion criteria. Most (59.6%) were female patients, and the mean age at the time of EMPD diagnosis was 70.8±10.1 years. Most (82%) of the 161 patients had at least 1 cancer screening test performed, though screening practices varied widely. Of those screened for an underlying malignancy, 17 distant, noncontiguous malignancies were identified in 15 patients (11.4%), with prostate (n=5), urinary tract (n=5), and breast (n=2) malignancies found most frequently. Most malignancies were identified by urine cytology, mammography, and prostate-specific antigen blood test. Of all patients, 37 (23.0%) had an underlying contiguous malignancy identified by pathology. CONCLUSION: All patients diagnosed with EMPD should undergo cancer screening. At minimum, evaluation should include age-appropriate screening and the addition of urine cytology, mammography, and prostate-specific antigen blood test-if not already performed-may be of particular use. An algorithm for evaluation of patients with newly diagnosed EMPD is proposed.