Treatment options in the advanced and recurrent setting for endometrial cancer: an update.

INTRODUCTION: Uterine cancer is the most common gynecologic malignancy in women and is projected to surpass ovarian cancer as the deadliest gynecologic malignancy in the United States in 2024. Additionally, rates of advanced and high-risk uterine cancer have been on the rise in the United States, demonstrating a need for innovation in treatment options. There have been multiple recent trials investigating the incorporation of novel agents in the treatment of advanced and recurrent endometrial cancer. AREAS COVERED: This article will discuss the current landscape of the treatment of advanced and recurrent endometrial cancer, focusing on recent phase III trials published or presented on with the incorporation of immunotherapy and other novel therapeutics while also reviewing promising phase I and II trials in the field. Clinical trials were identified via clinicaltrials.gov and a PubMed literature search was performed (initially February 2024, updated May 2024). EXPERT OPINION: The treatment field is promising for patients as many of these trials appear to offer progression free and overall survival benefits in a disease with a historically poor prognosis. Molecular profiling of endometrial cancer will be the backbone of treatment paradigms in the future.

Patient-reported outcomes at discontinuation of anti-angiogenesis therapy in the randomized trial of chemotherapy with bevacizumab for advanced cervical cancer: an NRG Oncology Group study.

INTRODUCTION: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab. METHODS: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240. RESULTS: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain. DISCUSSION: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.

The rationale for the use of non-platinum chemotherapy doublets for metastatic and recurrent cervical carcinoma.

Ongoing drug discovery and synergy in cytotoxic combinations have served as the dominant theme for clinical research in women with metastatic and recurrent cervical cancer. The results of the most recent phase III randomized clinical trials conducted by the Gynecologic Oncology Group in this population evaluated the tolerability and efficacy of cisplatin-based chemotherapy doublets. Possibly as a consequence of the increasing use of radiosensitizing cisplatin with concurrent pelvic radiotherapy for treatment of locally advanced disease prior to recurrence, the response rates obtained with platinum-based regimens have decreased with each successive trial. There is clearly a need for a re-appraisal of therapeutic options for women with recurrent and metastatic cervical cancer, many of whom may harbor platinum-resistant clones. In this article we will provide a rationale for the use of non-platinum-based chemotherapy doublets for this patient population.

A phase 2 evaluation of irofulven as second-line treatment of recurrent or persistent intermediately platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group trial.

This multicenter phase 2 trial was conducted by the Gynecologic Oncology Group to evaluate the activity and the safety of irofulven in patients with recurrent epithelial ovarian cancer. Eligible patients had documented recurrent ovarian cancer 6 to 12 months after receiving a front-line platinum-based regimen and no other chemotherapy. Patients were required to have measurable disease, performance status of 0 to 2, and adequate bone marrow, hepatic, and renal functions before study entry. The dose of irofulven was 0.45 mg/kg intravenously on days 1 and 8 every 21 days. Responses were defined by Response Evaluation Criteria in Solid Tumors. Fifty-five of 61 enrolled patients were evaluable for response and toxicity. There were 7 partial responses (12.7%), and 30 patients (54.6%) had stable disease. Median progression-free and overall survival were 6.4 months (1.3-37.5 months) and 22.1 months or more (2.8-57.8+ months), respectively. Patients received a median of 3 cycles (range, 1-21) of protocol therapy. Grade 4 hematologic toxicity was limited to reversible neutropenia and thrombocytopenia. Grade 4 nonhematologic toxicity was limited to one patient with anorexia and another with hypomagnesemia. Irofulven administered at this dose and schedule was well tolerated but had modest activity as a single agent.

Primary prevention of uterine cervix cancer: focus on vaccine history and current strategy.

Primary prevention of uterine cervix cancer spans the gamut of human papillomavirus vaccine development, dietary adjustment, chemoprevention, and risk reduction. Lifestyle and social behaviors impact on risk for cervical cancer. Before examining the growing body of molecular evidence, animal studies, and phase I clinical trials that suggest that a virus-based vaccine for cervical cancer may soon become a reality, one must reflect on what has gone before in the vaccine-based battle with viral disease.