Relationship between social support, quality of life, and Th2 cytokines in a biobehavioral cancer survivorship trial.

ObjectiveBenefits of social support (SS) during cancer survivorship are complex. This study examines change in SS over time in cervical cancer (CXCA) survivors who have completed definitive treatment and how changing SS impacts quality of life (QOL) and T-helper type 2 (Th2) cytokines.MethodsWe conducted a randomized trial in 204 CXCA survivors to test if psychosocial telephone counseling (PTC) could improve QOL compared to usual care (UC). Although PTC did not target SS, data were collected at baseline, 4 and 9 months post-enrollment using the Medical Outcomes Survey Social Support scale. Biospecimens were collected to investigate associations with patient-reported outcomes. Data were analyzed using multivariate linear models and stepwise regression.ResultsParticipants' mean age was 43. PTC participants experienced increasing SS compared to UC at 4 months (PTC-UC = 5.1; p = 0.055) and 9 months (PTC-UC = 6.0; p = 0.046). Higher baseline SS and increasing SS were independently associated with improved QOL at 4 and 9 months after adjusting for patient characteristics (p < 0.05). Differences between study arms were not statistically significant. Improvements in QOL at 4 months were observed with increases in emotional/informational and tangible SS. Increasing SS predicted significant longitudinal decreases in IL-4 and IL-13 at 4 months that were larger in the PTC arm (interactions p = 0.041 and p = 0.057, respectively).ConclusionImproved SS was significantly associated with improved QOL independent of patient characteristics and study arm. Decreasing Th2 cytokines with increasing SS and QOL are consistent with a biobehavioral paradigm in which modulation of the chronic stress response is associated with shifts in immune stance

Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer

Cervical cancer; Checkpoint inhibitor; ImmunotherapyCáncer de cuello uterino; Inhibidor de puntos de control; InmunoterapiaCàncer cervical; Inhibidor de punts de control; ImmunoteràpiaObjective This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer. Methods Eligible patients were 18 years or older with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. Balstilimab was administered intravenously at 3 mg/kg once every two weeks, for up to 24 months. The primary endpoint was objective response rate (ORR, RECIST v1.1) as assessed by an independent review committee. Results At data cutoff, 161 women (median age, 53 years [range 25–81]) were enrolled and treated with balstilimab. Of these, 140 had measurable disease at baseline and one prior line of platinum-based therapy in the metastatic, persistent, or recurrent setting; these patients were included in the efficacy analyses. The ORR was 15% (95% CI, 10.0%–21.8%) and included 5 patients with a complete response and 16 with a partial response. The median duration of response was 15.4 months. In patients with PD-L1-positive tumors the ORR was 20%, however patients with PD-L1-negative tumors also responded to balstilimab (ORR, 7.9%). Responses were not restricted to tumors of squamous cell histology, and an ORR of 12.5% was seen in the subset of patients with cervical adenocarcinoma. The disease control rate was 49.3% (95% CI, 41.1%–57.5%). Immune-mediated enterocolitis (3.1%) and diarrhea (1.9%) were the most common grade 3 or higher treatment-related adverse events. Conclusion Balstilimab demonstrated meaningful and durable clinical activity, with manageable safety, in patients with previously-treated, recurrent/metastatic cervical cancer.This study was funded by Agenus Inc

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45)

Cáncer de ovarios; MonoterapiaCàncer d'ovaris; MonoteràpiaOvarian cancer; MonotherapyPURPOSE ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo. METHODS Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer

Chemotherapy; Quality of life; SymptomsQuimioterapia; Calidad de vida; SíntomasQuimioteràpia; Qualitat de vida; SímptomesBackground In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. Methods Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1–16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. Results Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77–13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08–12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. Conclusions Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.This work was supported by Regeneron Pharmaceuticals, Inc., and Sanofi

Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2

AbstractObjectiveGenetic predisposition to ovarian cancer is well documented. With the advent of next generation sequencing, hereditary panel testing provides an efficient method for evaluating multiple genes simultaneously. Therefore, we sought to investigate the contribution of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel.MethodsSubjects were referred for multi-gene panel testing between February 2012 and March 2014. Clinical data was ascertained from requisition forms. The incidence of pathogenic mutations (including likely pathogenic), and variant of unknown significance were then calculated for each gene and/or patient cohort.ResultsIn this cohort of 911 subjects, panel testing identified 67 mutations. With 7.4% of subjects harboring a mutation on this multi-gene panel, the diagnostic yield was increased, compared to testing for BRCA1 and BRCA2 mutations alone. In the ovarian cancer probands, the most frequently mutated genes were BRIP1 (n=8; 1.72%) and MSH6 (n=6; 1.29%). In the breast cancer probands, mutations were most commonly observed in CHEK2 (n=9; 2.54%), ATM (n=3; 0.85%), and TP53 (n=3; 0.85%).ConclusionsAlthough further studies are needed to clarify the exact management of patients with a mutation in each gene, this study highlights information that can be captured with panel testing and provides support for incorporation of panel testing into clinical practice

Left Ventricular Ejection Fraction in Patients With Ovarian Cancer Treated With Avelumab, Pegylated Liposomal Doxorubicin, or Both

In the phase III JAVELIN Ovarian 200 trial, 566 patients with platinum-resistant/refractory ovarian cancer were randomized 1:1:1 to receive avelumab alone, avelumab plus pegylated liposomal doxorubicin (PLD), or PLD alone. Cardiac monitoring was included for all patients. We report left ventricular ejection fraction (LVEF) data from the trial. Grade ≥3 cardiac adverse events (AEs) occurred in 4 (2.1%), 1 (0.5%), and 0 patients in the avelumab, combination, and PLD arms, respectively. LVEF decreases of ≥10% to below institutional lower limit of normal at any time during treatment were observed in 1 (0.8%), 3 (1.9%), and 2 (1.5%) patients, respectively; 4 had subsequent assessments, and these showed transient decreases. No patient had a cardiovascular AE related to LVEF decrease. This analysis is, to our knowledge, the first analysis of LVEF in patients receiving immune checkpoint inhibitors. CLINICALTRIALS.GOV IDENTIFIER: NCT02580058

Features of the cervicovaginal microenvironment drive cancer biomarker signatures in patients across cervical carcinogenesis

Persistent human papillomavirus (HPV) infection is the vital factor driving cervical carcinogenesis; however, other features of the local cervicovaginal microenvironment (CVM) may play a critical role in development of precancerous cervical dysplasia and progression to invasive cervical carcinoma (ICC). Here we investigated relationships between locally secreted cancer biomarkers and features of the local CVM to better understand the complex interplay between host, virus and vaginal microbiota (VMB). We enrolled women with ICC, high- and low-grade squamous intraepithelial lesions, as well as, HPV-positive and healthy HPV-negative controls. A broad range of cancer biomarkers was present in the local CVM and specifically elevated in ICC patients. The majority of cancer biomarkers were positively correlated to other biomarkers and linked to genital inflammation. Several cancer biomarkers were also negatively correlated to Lactobacillus abundance and positively correlated with abnormal vaginal pH. Finally, a hierarchical clustering analysis of cancer biomarkers and immune mediators revealed three patient clusters, which varied in levels of cancer biomarkers, genital inflammation, vaginal pH and VMB composition. Specific cancer biomarkers discriminated patients with features of the CVM, such as high genital inflammation, elevated vaginal pH and dysbiotic non-Lactobacillus-dominant VMB, that have been associated with HPV persistence, dysplasia and progression to ICC.Flinn Foundation [1974]; National Institutes of Health NIAID [1R15AI113457-01A1]; National Institutes of Health NCI [P30 CA023074]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Differentiating Squamous Cell Carcinoma of the Cervix and Epithelioid Trophoblastic Tumor

Epithelioid trophoblastic tumor (ETT) is a recently described subtype of gestational trophoblastic neoplasia (GTN). Its diagnosis requires a high level of suspicion because it is often mistaken for more common cervical or uterine corpus epithelial neoplasms

Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study

PURPOSE: In the randomized phase III trial, Gynecologic Oncology Group (GOG) protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria. EXPERIMENTAL DESIGN: Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0-1 factor), mid-risk (2-3 factors), and high-risk (4-5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy. RESULTS: For the entire population (n = 452), high-risk patients had significantly worse OS (P < 0.0001). The HRs of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 [95% confidence interval (CI), 0.63-2.24], 1.11 (95% CI, 0.82-1.5), and 0.84 (95% CI, 0.50-1.42), respectively. The HRs of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI, 0.51-1.83; P = 0.9087), 0.673 (95% CI, 0.5-0.91; P = 0.0094), and 0.536 (95% CI, 0.32-0.905; P = 0.0196), respectively. CONCLUSIONS: This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real-world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8-month increase in median OS)