Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial.

BACKGROUND: CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC). METHODS: Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07). CONCLUSIONS: CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509). TRIAL REGISTRATION: NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.

A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy.

OBJECTIVE: To develop a nomogram to predict overall survival (OS) in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy. METHODS: A multicenter retrospective study was conducted. Potential prognostic variables included age; stage; grade; histology; performance status; residual disease; presence of ascites and/or pleural effusions; number of chemotherapy regimens, treatment-free interval (TFI) prior to bevacizumab administration, and platinum sensitivity. Multivariate analysis was performed using Cox proportional hazards regression. The predictive model was developed into a nomogram to predict five-year OS. RESULTS: 312 women with recurrent ovarian cancer treated with bevacizumab and chemotherapy were identified; median age was 59 (range: 19-85); 86% women had advanced stage (III-IV) disease. The majority had serous histology (74%), high grade cancers (93.5%), and optimal cytoreductions (69.5%). Fifty-one percent of women received greater than two prior chemotherapeutic regimens. TFI (AHR=0.98, 95% CI 0.97-1.00, p=0.022) was the only statistically significant predictor in a multivariate progression-free survival (PFS) analysis. In a multivariate OS analysis, prior number of chemotherapy regimens, TFI, platinum sensitivity, and presence of ascites were significant. A nomogram to predict five-year OS was constructed and internally validated (bootstrap-corrected concordance index=0.737). CONCLUSION: Our multivariate model identified prior number of chemotherapy regimens, TFI, platinum sensitivity, and the presence of ascites as prognostic variables for OS in women with recurrent ovarian cancer treated with bevacizumab combined with chemotherapy. Our nomogram to predict five-year OS may be used to identify women who may benefit from bevacizumab and chemotherapy, but further validation is needed.

Cost-effectiveness of adjuvant radiotherapy in intermediate risk endometrial cancer.

OBJECTIVES: Endometrial cancer is the most common gynecologic malignancy in the United States. Adjuvant radiotherapy in patients with intermediate risk disease (stage IB, IC, and occult stage II) is controversial. Despite no proven survival advantage, a significant number of women undergo this treatment annually. The purpose of this study was to compare the estimated health and economic outcomes for adjuvant whole pelvic radiotherapy to no treatment with salvage therapy for recurrence. METHODS: A decision analytic model was created to estimate the costs of adjuvant pelvic radiotherapy versus no adjuvant radiotherapy in patients with intermediate risk endometrial cancer. Data used was gathered from published literature and institutional data on costs. The model incorporates complications, recurrence rates, treatment of recurrence, and survival in each group. RESULTS: In the base case analysis, adjuvant pelvic radiation reduced the recurrence rate by 50%. Cost-effectiveness as measured by cost per recurrence prevented was highly sensitive to the probability of recurrence and the efficacy of adjuvant therapy. In our model the mean costs of Strategy 1 with observation and treatment reserved until the time of recurrence would be $5016. In contrast the mean cost of Strategy 2 which incorporated adjuvant radiotherapy would be $21,159. Cost per recurrence prevented based on the incremental cost-effectiveness is thus $225,215. In the highest risk subgroup, using the upper limit of the 90% confidence limit of efficacy seen in GOG Protocol 99, cost/recurrence prevented was approximately $50,000. Results did not differ when using parameters solely from GOG 99 or PORTEC. CONCLUSIONS: Although adjuvant pelvic radiation does not appear to improve survival for intermediate risk endometrial cancer patients, it does prevent recurrences, at a net positive cost compared to no therapy. Data are not currently available to incorporate quality of life information into cost-effectiveness analyses. Obtaining such data would allow cost/quality-adjusted life year gained to be estimated. This information is necessary to determine if the extra costs of adjuvant radiotherapy in patients with intermediate risk endometrial cancer are acceptable by current health care policy standards.