Dana M. Chase

Real-world post-2020 first-line maintenance treatment patterns in patients with advanced ovarian cancer in the US

To describe first-line maintenance (1LM) treatment patterns since 1 January 2020, for real-world patients with newly diagnosed advanced ovarian cancer (aOC). This retrospective study used a US-nationwide electronic health record-derived deidentified database. Eligible patients were aged ≥ 18 years with stage III/IV epithelial OC and initiated first-line platinum-based chemotherapy±bevacizumab (index; 01Jan2020-28Feb2023). Baseline characteristics and 1LM treatment patterns were summarized overall and by Among 599 eligible patients (median [interquartile range] age, 67 [59-74] years; 59.8% White; 50.3% stage III disease), 15.5% had Fewer than half of included patients with aOC received 1LM treatment in the real-world setting. More work is needed to understand reasons underlying real-world 1LM treatment choice for patients with aOC.

ROCC/GOG-3043: a randomized controlled trial of robotic versus open surgery for early-stage cervical cancer

The Laparoscopic Approach to Cervical Cancer trial is the only randomized trial to date addressing the role of surgical approach in cervical cancer; however, this non-inferiority trial of minimally invasive surgery vs an open approach in patients undergoing radical hysterectomy for early-stage cervical cancer did not meet its primary end point of 4.5-year disease-free survival and was terminated early because of significantly worse disease-specific survival, overall survival, and locoregional recurrence in the minimally invasive surgery cohort. Our trial compares 3-year disease-free survival after robotic-assisted or abdominal radical or simple (in select cases) hysterectomy in early-stage cervical cancer. We hypothesize that disease-free survival is non-inferior after robotic-assisted vs abdominal radical or simple hysterectomy. This multi-center, randomized non-inferiority trial conducted through the Gynecologic Oncology Group has specified surgeon qualification criteria. It requires a pelvic magnetic resonance imaging scan in all patients before enrollment and will use 1:1 randomization to assign patients to robotic-assisted or abdominal hysterectomy. All surgeons must use specified tumor-containment techniques in both arms. It does not allow trans-cervical uterine manipulators. Patients with early-stage (2018 International Federation of Gynecology and Obstetrics stages IA2-IB2) cervical cancer. Histologic types are limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. Pelvic magnetic resonance imaging must confirm a tumor that is 4 cm or less without definitive extra-cervical spread. A simple hysterectomy is allowed in select cases after trial study principal investigator review. The primary end point is the 3-year disease-free survival between robotic-assisted or abdominal hysterectomy. The trial will randomly allocate 840 patients, with planned interim analysis for futility (oncologic safety) after we have randomly allocated 370 and 640 patients. 2030. ClinicalTrials.gov identifier: NCT04831580.

Correlation between progression-free survival and overall survival in patients with ovarian cancer after cytoreductive surgery: a systematic literature review

This analysis aimed to better define the relationship between progression-free survival and overall survival in adult patients with ovarian cancer (including fallopian tube or primary peritoneal cancer) following primary cytoreductive surgery or interval cytoreductive surgery. A systematic literature review was carried out across the Medline, Embase, and Cochrane Central databases on 7 July 2020 (date limits 1 January 2011 to 7 July 2020) to identify studies with the following eligibility criteria: clinical trials/observational studies including >200 patients with ovarian cancer aged ≥18 years, evaluating overall survival/progression-free survival following cytoreductive surgery by residual disease status in the United States, Europe, Japan, or China. Weighted linear regression models were used to assess any correlation between median progression-free survival and overall survival, and between logHR for progression-free survival and logHR for overall survival. Risk of bias was assessed for all included studies. Of the 50 studies reported, 43 were observational studies (41 retrospective and two prospective cohort studies), and seven were reporting for randomized clinical trials-of which four were retrospective data analyses. For analyses of the relationship between overall survival and progression-free survival, 21 studies were eligible. The weighted linear regression model showed a strong positive association between the two survival endpoints. Goodness-of-fit analysis measured the adjusted R Median progression-free survival was predictive of median overall survival. This correlation between progression-free survival and overall survival after primary treatment for ovarian cancer highlights the validity of progression-free survival as a primary endpoint. Observational studies contributed most data, with limited information on disease stage and histology.

Association of Multiple High-Risk Factors on Observed Outcomes in Real-World Patients With Advanced Ovarian Cancer Treated With First-Line Therapy

PURPOSE To identify risk factors for disease progression or death and assess outcomes by risk categories in real-world patients with advanced ovarian cancer. METHODS This retrospective study included adult patients from a nationwide electronic health record–derived deidentified database with stage III/IV ovarian cancer who received first-line therapy and had ≥12 weeks of follow-up after index date (end of first-line therapy). Factors predictive of time to next treatment and overall survival (OS) were assessed. Patients were grouped according to the cumulative number of high-risk factors present (stage IV disease, no debulking surgery or neoadjuvant therapy and interval debulking surgery, visible residual disease after surgery, and breast cancer gene [ BRCA] wild-type disease/unknown BRCA status), and time to next treatment and OS were assessed. RESULTS Region of residence, disease stage, histology, BRCA status, surgery modality, and visible residual disease were significant predictors of time to next treatment; age, Eastern Cooperative Oncology Group performance status, disease stage, BRCA status, surgery modality, visible residual disease, and platelet levels were significant predictors of OS (N = 1,920). Overall, 96.4%, 74.1%, and 40.3% of patients had at least 1, 2, or 3 high-risk factors, respectively; 15.7% of patients had all four high-risk factors. Observed median time to next treatment was 26.4 months (95% CI, 17.1 to 49.2) in patients with no high-risk factors and 4.6 months (95% CI, 4.1 to 5.7) in patients with four high-risk factors. Observed median OS was shorter among patients with more high-risk factors. CONCLUSION These results underscore the complexity of risk assessment and demonstrate the importance of assessing a patient's cumulative risk profile rather than the impact of individual high-risk factors. They also highlight the potential for bias in cross-trial comparisons of median progression-free survival because of differences in risk-factor distribution among patient populations.

Randomized phase III trial of adjuvant radiation versus chemoradiation in intermediate-risk, early-stage cervical cancer following radical hysterectomy and lymphadenectomy: results from NRG Oncology/GOG-263/KGOG 1008

To determine whether adjuvant chemoradiation (CRT) with weekly cisplatin improves recurrence-free survival (RFS) compared with radiation (RT) in pathologically proven intermediate risk early-stage cervical cancer following radical hysterectomy and lymphadenectomy. Post-surgical patients with stage I-IIA cervical cancer with pathologically noted intermediate risk factors including combinations of capillary lymphatic space involvement, stromal invasion, and tumor size were randomly assigned in a 1 : 1 ratio to receive either adjuvant CRT or RT (NCT01101451). Patients received conformal RT, or intensity modulated radiation therapy. In the CRT arm, 6 weekly cycles of cisplatin 40 mg/m Of the 340 randomized patients, 316 were eligible and most had Federation of Gynecology and Obstetrics (2009) stage IB Although RFS and OS favored CRT, the addition of cisplatin during RT did not statistically improve RFS or OS in cervical cancer patients with intermediate pathological risk factors following radical hysterectomy and lymphadenectomy. CRT increased grade 3 and 4 AEs with a transient decline in QoL.

Mirvetuximab soravtansine in the ovarian cancer treatment landscape: influence of prior taxane exposure on outcomes.

To evaluate prescribing patterns, toxicities, and outcomes among patients receiving mirvetuximab for platinum-resistant ovarian cancer. This retrospective study included patients with platinum-resistant ovarian cancer with high folate receptor alpha expression treated with mirvetuximab at a single institution (2018-2023). Patients were categorized based on treatment immediately preceding mirvetuximab: the taxane group received taxane treatment; the non-taxane group received other therapy. An age-matched cohort of platinum-resistant patients not treated with mirvetuximab was included for survival comparison. Statistical analyses included descriptive statistics, Kaplan-Meier curves, log-rank tests, Wilcoxon rank-sum tests, and Cox models. Forty-one patients received mirvetuximab, with a median of 8 cycles (range; 1-47). Grade ≥3 adverse events included ocular (n = 6; 15%), hematologic (n = 1; 2%), neuropathy (n = 1; 2%), and pneumonitis (n = 1; 2%). Dose reductions and delays occurred in 26 (63%) and 21 (51%) patients, respectively. Mirvetuximab was discontinued in 40 patients (98%), most commonly due to disease progression (n = 35; 88%). Mirvetuximab-treated patients had longer median overall survival from diagnosis compared to the age-matched cohort without mirvetuximab exposure (83.12 vs 52.14 months; HR 0.34, 95% CI 0.18 to 0.64, p < .001). Among patients who received taxane therapy immediately before mirvetuximab (n = 9), average treatment duration was 5 months (9 cycles), with no grade ≥3 neuropathy. In those who received a non-taxane regimen immediately before mirvetuximab (n = 32), average treatment duration was 6 months (8 cycles), with 1 patient (3%) experiencing grade ≥3 neuropathy. Median progression-free survival was similar between groups (5.49 vs 6.28 months; HR 1.30, 95% CI 0.61 to 2.78, p = .50), but overall survival was shorter in the taxane group (11.28 vs 21.02 months; HR 2.47, 95% CI 1.01 to 6.04, p = .048). Real-world experience with mirvetuximab demonstrated a favorable safety profile and clinical benefit in platinum-resistant ovarian cancer. Taxane therapy immediately preceding mirvetuximab was associated with shorter overall survival but not increased neurotoxicity.

Quality-adjusted time without symptoms of disease progression or toxicity of treatment in patients with primary advanced or recurrent endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel

In part 1 of the phase 3 RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer, dostarlimab plus carboplatin-paclitaxel significantly improved progression-free and overall survival vs placebo plus carboplatin-paclitaxel. Post hoc analyses examined the impact of adding dostarlimab to chemotherapy, compared with placebo plus chemotherapy, on quality-adjusted time without symptoms of disease progression or toxicity of treatment in this patient population. Patients were randomized 1:1 to receive dostarlimab/placebo plus chemotherapy every 3 weeks for 6 cycles, followed by dostarlimab/placebo monotherapy every 6 weeks for up to 3 years. Data from the first interim analysis (September 28, 2022) were used, and quality of life (QoL) was assessed with the EuroQoL 5-Dimensions 5-Level questionnaire. Quality-adjusted time without symptoms of disease progression or toxicity of treatment was calculated as the sum product of the restricted mean survival times spent in 3 mutually exclusive states: toxicity, time without symptoms of disease progression or treatment toxicity, and relapse, and utilized each state's corresponding QoL. In the dostarlimab and placebo arms, 241 and 246 patients were analyzed for safety, respectively. In the overall population, the mean (95% CI) duration of quality-adjusted time without symptoms of disease progression or toxicity of treatment was significantly longer in the dostarlimab arm (24.75 months [22.88 to 26.65 months]) than in the placebo arm (20.34 months [18.95 to 21.76 months]; the mean difference [95% CI] of 4.41 months [2.01 to 6.77 months], p < .001). Benefits in quality-adjusted time without symptoms of disease progression or toxicity of treatment after dostarlimab treatment were observed regardless of mismatch repair/microsatellite instability status or toxicity criteria used and were predominantly driven by the time without symptoms of disease. Dostarlimab plus carboplatin-paclitaxel treatment is associated with meaningful improvement in survival, avoidance of substantial toxicity, and maintenance of patient-reported QoL in patients with primary advanced or recurrent endometrial cancer.

Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification

Abstract Purpose: Endometrial cancer is highly prevalent and lacking noninvasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve the understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for noninvasive diagnostic and prognostic tests. Experimental Design: Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n = 66) and non-malignant conditions (n = 108), and global untargeted metabolomics was performed. Using the metabolite data (n = 920), we completed a multivariate biomarker discovery analysis. Results: We analyzed grade 1/2 endometrioid carcinoma (n = 53) and other endometrial cancer subtypes (n = 13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of proline (P &amp;lt; 0.0001), tryptophan (P &amp;lt; 0.0001), and glutamate (P &amp;lt; 0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q &amp;lt; 0.05) of sphingolipids, fatty acids, and glycerophospholipids was observed in endometrial cancer in a type-specific manner. Furthermore, cervicovaginal metabolites related to tumor characteristics, including tumor size and myometrial invasion. Conclusions: Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement in diagnosis. The metabolic dysregulation described in this article linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighboring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of noninvasive diagnostics can improve both the acceptability and accessibility of diagnosis.

A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer

This is a randomized controlled trial to compare survival for patients who undergoe robotic assisted laparoscopy versus open hysterectomy and lymph node assessment for the treatment of early stage cervical cancer.