Sarah M. Temkin

A Phase Ib Study of Indirect Immunization with Oregovomab and Toll-like-Receptor-3 Stimulation with Hiltonol® in Patients with Recurrent Platinum-Resistant Ovarian Cancer

Objectives: This phase Ib study assessed the safety and compatibility of indirect oregovomab immunization and Toll-like-receptor-3 (TLR3) stimulation with immune adjuvant Hiltonol® (poly-ICLC) and induced clinically relevant CA125-specific anti-tumor immunity in heavily pretreated patients with progressive platinum-resistant ovarian cancer (PROC). Methods: Patients with elevated serum CA125 level >50 U/mL received four intravenous infusions with 2 mg oregovomab followed by 2 mg Hiltonol® intramuscular 30 min and 48 h post-oregovomab at weeks 0, 3, 6, and 9. At week 12, imaging was performed, and salvage chemotherapy was allowed post-progression per the investigator’s discretion. The Fifth/final oregovomab with Hiltonol® infusion was given at week 16. Results: Fifteen enrolled patients were analyzed for safety and efficacy. Thirteen (87%) patients completed at least three Hiltonol® infusions with oregovomab, specifically, two cycles (n = 2), three cycles (n = 2), four cycles (n = 3), and five cycles (n = 8). Adverse events included mild fatigue, flu-like symptoms, chills, axillary pain, and injection site discomfort in 13 (87%) patients. Serious adverse events were reported in seven (47%) patients, including Grade 3 hypertension (n = 2), thrombocytopenia (n = 1), and Grade 3 events attributed to underlying disease (n = 4). Ten (67%) patients had disease progression, three (20%) had stable disease, and two were unevaluable. Early humoral response by week 6 was observed in seven of nine (77%) patients, median progression-free survival was 2.7 months (95% confidence interval [CI]: 2.2, 3.3), and median overall survival was 15.0 months (95% CI: 8.2–23.9). Conclusions: The safety and compatibility of combining oregovomab with Hiltonol® have been demonstrated in this study. The potential to enhance activity of chemotherapy using oregovomab indirect immunization and Hiltonol® stimulation is proposed.

Federal Cervical Cancer Collaborative: Improving cervical cancer prevention through vaccination, screening, and management in safety‐net settings of care

AbstractThe Federal Cervical Cancer Collaborative (FCCC) was established by the Health Resources and Services Administration Office of Women’s Health and its interagency partners within the U.S. Department of Health and Human Services. Its primary mission, aligned with the goals of the Cancer Moonshot (https://www.cancer.gov/research/key‐initiatives/moonshot‐cancer‐initiative/implementation/prevention‐early‐detection), is to accelerate control of cervical cancer within safety‐net settings of care. This interagency partnership works in close collaboration to reduce disparities in cervical cancer care, particularly among populations that are geographically isolated, economically challenged, and medically underserved. The FCCC bridges federal priorities of cancer research from the National Institutes of Health National Cancer Institute to health care delivery in Health Resources and Services Administration–supported and safety‐net settings of care. In this commentary, FCCC activities are discussed to improve cervical cancer prevention and control through vaccination, screening, and management of preinvasive cervical disease in safety‐net settings of care. These activities include the development and implementation of an evidence‐based, action‐oriented provider toolkit and federal opportunities report. The FCCC’s efforts to increase the readiness of safety‐net settings of care to implement the 2019 American Society for Colposcopy and Cervical Pathology Risk‐Based Management Consensus Guidelines for patients with abnormal cervical cancer screening results are discussed. Also described are the results from a survey of National Cancer Institute–designated cancer centers, designed to inform future efforts to strengthen referrals and care coordination with safety‐net settings of care.

Challenges in implementation of molecular classification in early stage endometrial cancer—An NRG Oncology cooperative group mixed‐methods study

AbstractBackgroundProfessional guidelines recommend molecular profiling for mismatch repair (MMR), p53, and polymerase epsilon (POLE) status in endometrial cancer (EC). However, adoption in the United States has not been documented, and barriers to the implementation of testing have not been described.MethodsIn this mixed‐methods study, implementation science frameworks were used to develop a quantitative survey. Gynecologic oncologists, medical oncologists, radiation oncologists, and pathologists affiliated with NRG Oncology programs were contacted through snowball sampling and were surveyed during 2022–2023. A subset of respondents was interviewed. Statistical and thematic analyses were performed.ResultsAt least 403 NRG Oncology‐affiliated providers were contacted for the survey, and 107 (26.6%) responded. Greater than 90% of respondents perceived POLE, MMR, and p53 status as important for clinical care. MMR and p53 tests were perceived as easy to obtain, but only 24.2% of respondents reported that POLE testing was moderately or very easy to obtain. Respondents from academic sites reported better access to molecular classification and perceived greater importance of molecular classification compared with respondents from community sites. In thematic analysis of 13 qualitative interviews, cost concerns were reported as large barriers to testing. Interviewees reported a desire for prospective data to guide treatment selection based on classification results.ConclusionsAlthough integrating molecular classification into standard pathologic reporting is recommended, and clinicians perceive molecular profiling in early stage EC as important, survey respondents noted significant implementation barriers. Implementation challenges that differ between community oncology and academic practice settings were identified. Strategies to improve equitable access to molecular classification of early stage EC are needed.