Landrum, Lisa M.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cervical Cancer provide diagnostic workup, staging, and various treatment recommendations for cervical cancer based on clinical and surgical staging. This selection from the NCCN Guidelines for cervical cancer specifically focuses on diagnosis and workup, principles of staging and surgery, and primary treatment recommendations for early-stage and advanced disease and provides a detailed overview of systemic therapy recommendations for cervical cancer.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer and uterine sarcoma. The NCCN Cervical Uterine Panel meets at least annually to review comments from reviewers within their institutions; examine relevant new data from publications, abstracts, and recent FDA approvals; and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s deliberations on the new FIGO 2023 staging system and updates on the new systemic therapy recommendations for the management of endometrial cancer.

3 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

3 Background: Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab (B), a humanized anti-VEGF monoclonal antibody, has shown single-agent activity in pretreated recurrent disease. We aimed to evaluate B in chemotherapy (CTX)-naive recurrent/persistent/metastatic cervical cancer. Methods: Using a 2x2 factorial design, patients were randomly assigned to CTX with or without B 15 mg/kg. The CTX regimens included cisplatin 50 mg/m2 plus paclitaxel 135-175 mg/m2 and topotecan 0.75 mg/m2 d1-3 plus paclitaxel 175 mg/m2d1. Cycles were repeated every 21 days until disease progression, unacceptable toxicity, or complete response. Overall survival (OS) was the primary endpoint with a reduction in the hazard of death by 30% using anti-VEGF therapy considered important (90% power, 1-sided alpha=2.5%). Final analysis was planned when 346 deaths were observed. Results: 452 patients were accrued from 4/6/09 to 1/3/12. The scheduled interim analysis occurred after 174 patients had died and showed that the topotecan-paclitaxel backbone was not superior to the cisplatin-paclitaxel backbone. A second interim analysis was conducted after 271 deaths. A total of 225 patients received CTX alone and 227 patients received CTX plus B. The randomized treatment groups were similar with regard to age, histology, performance status, previous platinum as a radiosensitizer, and recurrence, persistence, or advanced disease. The B-to-no-B hazard ratio (HR) of death was 0.71 (97.6% CI 0.54-0.95; 1-sided p=0.0035). Median survival was 17 m (CTX plus B) and 13.3 m (CTX alone). The RR were 48% (CTX plus B) and 36% (CTX alone) (p=0.0078). Treatment with B was associated with more grade 3-4 bleeding (5 vs 1%) thrombosis/embolism (9 vs 2%), and GI fistula (3 vs 0%). Conclusions: For the first time a targeted agent significantly improved OS in gynecologic cancer. The second interim analysis crossed the boundary for efficacy, warranting early release of this information. The nearly 4-month increase in median OS with the addition of B to CTX in women with recurrent cervical cancer is considered to be clinically significant. Clinical trial information: NCT00803062.

Abstract 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). Clin Cancer Res; 21(24); 5480–7. ©2015 AACR.