Ramondetta, Lois Michelle

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.

5595 Background: Endometrial cancer is the most common cancer of the female genital tract. It affected 41,200 women in the year 2006 and caused 7,350 deaths. Therapy options for recurrent/advanced endometrial cancer are limited. Treatment with radiation and chemotherapy has shown only limited success. Methods: In a phase II IRB approved trial, Mifepristone was given to patients with progesterone receptor positive advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma at a dose of 200mg/day orally. Patients were evaluated every 4 weeks to assess treatment-related toxicities and response. Imaging was obtained initially at 8 weeks then every 12 weeks for evaluation of response. Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to assess toxicity. Results: Twelve of 13 enrolled patients were evaluable for response in the first phase of accrual. Stable disease was noted in 3/12 (16, 20, and 44+ weeks). Two were endometrioid endometrial cancer and one with LGESS. No complete responses were seen, one patient remains in treatment. The most frequently reported grade 1–2 tumor related toxicities were anorexia, mood alterations, and fatigue (55%). Twenty-seven percent had asymptomatic elevations of ACTH. The most common Grade 3 toxicities were fatigue and dyspnea (27% and 18%). Only one patient experienced a Grade 4 dyspnea. No serious treatment-related adverse events occurred. Conclusions: Single agent mifepristone in patients with recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma showed no complete responses. Stable disease was reported 25%, one patient remains stable at 44 weeks. Recent reports suggests that mifepristone may also work via non hormonal targets while single agent mifepristone has minimal activity in this setting. Further evaluation in combination therapy in endometrial cancer should be considered. No significant financial relationships to disclose.

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.

BACKGROUNDPreclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta‐adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]).METHODSA multicenter review of 1425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta‐blocker use during chemotherapy and those without beta‐blocker use.RESULTSThe median age of patients in the current study was 63 years (range, 21‐93 years). The sample included 269 patients who received beta‐blockers. Of those, 193 (71.7%) were receiving beta‐1–adrenergic receptor selective agents, and the remaining patients were receiving nonselective beta antagonists. The primary indication for beta‐blocker use was hypertension but also included arrhythmia and postmyocardial infarction management. For patients receiving any beta‐blocker, the median overall survival (OS) was 47.8 months versus 42 months for nonusers (P =.04). The median OS based on beta‐blocker receptor selectivity was 94.9 months for those receiving nonselective beta‐blockers versus 38 months for those receiving beta‐1–adrenergic receptor selective agents (P<.001). Hypertension was associated with decreased OS compared with no hypertension across all groups. However, even among patients with hypertension, a longer median OS was observed among users of a nonselective beta‐blocker compared with nonusers (38.2 months vs 90 months; P<.001).CONCLUSIONSUse of nonselective beta‐blockers in patients with EOC was associated with longer OS. These findings may have implications for new therapeutic approaches. Cancer 2015;121:3435–43. © 2015 American Cancer Society.