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Impact of cytokine use on survival in the first-line treatment of ovarian cancer: A Gynecologic Oncology Group study
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
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laparotomy (63% vs 47%, p b 0.01). Patients with a negative second-look surgery had a lower nadir CA 125 compared to positive second-look, 9 and 12 U/mL respectively (p b 0.01). Conclusions: These results show that patients with IV/IP chemotherapy had similar CA 125 nadir values compared to IV therapy. Our results confirm that patients with low nadir CA 125 b10 U/mL have an improved PFS and OS, irrespective of treatment type. Additionally, patients treated with IV/IP chemotherapy were more likely to have a negative second-look surgery and have lower nadir CA 125. The use of nadir CA 125 value may help identify patients who are at risk for disease recurrence even with a normal CA 125.
doi:10.1016/j.ygyno.2011.12.064
64 Impact of cytokine use on survival in the first-line treatment of ovarian cancer: A Gynecologic Oncology Group study E. Rossi1, M. Brady2, J. Thigpen3, F. Stehman1, R. Burger4. 1Indiana University School of Medicine, Indianapolis, IN, 2Roswell Park Cancer Institute, Buffalo, NY, 3University of Mississippi Medical, Jackson, MS, 4 Fox Chase Cancer Center, Philadelphia, PA.
Objective: Cytotoxic chemotherapy often causes neutropenia and anemia. Granulocyte colony-stimulating factor (G-CSF) and erythropoietin-stimulating agents (ESA) may be used to support patients through therapy. We assessed whether the use of G-CSF or ESA was associated with the risk of death in patients being treated for ovarian cancer. Methods: Eligible patients had newly diagnosed, untreated epithelial ovarian peritoneal, or fallopian tube cancer following abdominal surgery, and had stage III or stage IV disease. The randomly assigned regimens were chemotherapy (paclitaxel plus carboplatin for cycles 1 through 6) plus placebo cycles 2 through 22; chemotherapy plus concurrent bevacizumab cycles 2 through 6 plus placebo cycles 7 through 22; or chemotherapy plus concurrent bevacizumab cycles 2 through 22. Infusions were administered on day 1 of a 21-day cycle. Guidelines for the administration of G-CSF and ESA were provided in the protocol. Results: One thousand eight hundred and seventy-three women were enrolled, with no differences in known clinical and pathologic variables among assigned treatment groups, though there were differences in the use of G-CSF and ESA. Nine patients received no protocol-directed therapy, leaving 1864 patients evaluable for this review. There were 1125 patients who received neither ESA nor G-CSF; 311 received G-CSF but no ESA; 241 patients received ESA but no G-CSF; and 187 who received both. The median survival following a 5-month landmark from the start of treatment was 39 vs 43 months for those who did vs did not receive an ESA (Figure) and 45 vs 42 months for those who did vs did not receive G-CSF. Conclusions: Neither the addition of ESA nor G-CSF had a significant negative impact on survival after adjustment of prognostic factors among patients with advanced ovarian cancer receiving chemotherapy. ESA may appear to be associated with shorter observed survival because factors that are prognostic for ESA use are also prognostic for progression-free and overall survival. Failure to properly adjust for known prognostic factors has probably caused other reports to ascribe a negative impact to these agents.
doi:10.1016/j.ygyno.2011.12.065
65 Early onset hypertension predicts prolonged progression-free and overall survival in women with mullerian duct adenocarcinomas treated with bevacizumab C. Christie1, E. Ross2, M. Slifker2, D. Warshal3, J. Aikins3, R. Burger2. 1 Cooper University Hospital, Voorhees, NJ, 2Fox Chase Cancer Center, Philadelphia, PA, 3Cooper University Hospital, Camden, NJ. Objective: Bevacizumab has demonstrated therapeutic benefit in the front-line and recurrent disease setting for women with advanced Mullerian duct adenocarcinomas. Hypertension (HTN) is a well-known adverse effect observed with anti-VEGF agents such as bevacizumab. We hypothesized that early-onset hypertension requiring medical management could be predictive of treatment efficacy in this patient population. Methods: This historical cohort study included patients with endometrial, primary peritoneal, fallopian tube, and ovarian adenocarcinoma for whom bevacizumab was initiated between 2004 and 2010 at Fox Chase Cancer Center and Cooper University Hospital. The primary analysis was progression-free survival (PFS) by RECIST as a function of National Cancer Institute Common Toxicity Criteria version 3.0 grade ≥ 2 HTN developing or not developing within 8 weeks of treatment initiation. Secondary endpoints included overall survival (OS) and response rate (RR) by RECIST. Differences in PFS and OS between cohorts were evaluated using the logrank test and Cox proportional hazards regression, and differences in response rate were analyzed using the Fisher's exact test. Results: The study population consisted of 87 patients of whom 28 (32%) developed early-onset HTN. For the 50 patients with measurable disease, there was no significant difference in RR between the 15 who developed early HTN (RR = 53%) and those who did not (RR = 51%). In an unadjusted analysis, median PFS was 14.0 months for those who developed early HTN versus 7.7 months for those who did not (P = 0.0796). After adjusting for age and disease status (optimal stage III; suboptimal stage III & stage IV; recurrence-platinum sensitivity), patients who developed early HTN had a 55% reduction (p = 0.029, 95% CI = 8%, 78%), in the hazard of progression relative to patients who did not. In an unadjusted analysis, median OS was 17.6 months for those who developed early HTN versus 11 months for those that did not (P = 0.103). The adjusted analysis demonstrated that those with early HTN had a 66% reduction (p = 0.012; [95% CI =22%, 86%]) in the hazard of death relative to patients who did not. Conclusions: Our data suggest that after adjustments for important prognostic factors, PFS and OS are significantly prolonged for patients with
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laparotomy (63% vs 47%, p b 0.01). Patients with a negative second-look surgery had a lower nadir CA 125 compared to positive second-look, 9 and 12 U/mL respectively (p b 0.01). Conclusions: These results show that patients with IV/IP chemotherapy had similar CA 125 nadir values compared to IV therapy. Our results confirm that patients with low nadir CA 125 b10 U/mL have an improved PFS and OS, irrespective of treatment type. Additionally, patients treated with IV/IP chemotherapy were more likely to have a negative second-look surgery and have lower nadir CA 125. The use of nadir CA 125 value may help identify patients who are at risk for disease recurrence even with a normal CA 125.
doi:10.1016/j.ygyno.2011.12.064
64 Impact of cytokine use on survival in the first-line treatment of ovarian cancer: A Gynecologic Oncology Group study E. Rossi1, M. Brady2, J. Thigpen3, F. Stehman1, R. Burger4. 1Indiana University School of Medicine, Indianapolis, IN, 2Roswell Park Cancer Institute, Buffalo, NY, 3University of Mississippi Medical, Jackson, MS, 4 Fox Chase Cancer Center, Philadelphia, PA.
Objective: Cytotoxic chemotherapy often causes neutropenia and anemia. Granulocyte colony-stimulating factor (G-CSF) and erythropoietin-stimulating agents (ESA) may be used to support patients through therapy. We assessed whether the use of G-CSF or ESA was associated with the risk of death in patients being treated for ovarian cancer. Methods: Eligible patients had newly diagnosed, untreated epithelial ovarian peritoneal, or fallopian tube cancer following abdominal surgery, and had stage III or stage IV disease. The randomly assigned regimens were chemotherapy (paclitaxel plus carboplatin for cycles 1 through 6) plus placebo cycles 2 through 22; chemotherapy plus concurrent bevacizumab cycles 2 through 6 plus placebo cycles 7 through 22; or chemotherapy plus concurrent bevacizumab cycles 2 through 22. Infusions were administered on day 1 of a 21-day cycle. Guidelines for the administration of G-CSF and ESA were provided in the protocol. Results: One thousand eight hundred and seventy-three women were enrolled, with no differences in known clinical and pathologic variables among assigned treatment groups, though there were differences in the use of G-CSF and ESA. Nine patients received no protocol-directed therapy, leaving 1864 patients evaluable for this review. There were 1125 patients who received neither ESA nor G-CSF; 311 received G-CSF but no ESA; 241 patients received ESA but no G-CSF; and 187 who received both. The median survival following a 5-month landmark from the start of treatment was 39 vs 43 months for those who did vs did not receive an ESA (Figure) and 45 vs 42 months for those who did vs did not receive G-CSF. Conclusions: Neither the addition of ESA nor G-CSF had a significant negative impact on survival after adjustment of prognostic factors among patients with advanced ovarian cancer receiving chemotherapy. ESA may appear to be associated with shorter observed survival because factors that are prognostic for ESA use are also prognostic for progression-free and overall survival. Failure to properly adjust for known prognostic factors has probably caused other reports to ascribe a negative impact to these agents.
doi:10.1016/j.ygyno.2011.12.065
65 Early onset hypertension predicts prolonged progression-free and overall survival in women with mullerian duct adenocarcinomas treated with bevacizumab C. Christie1, E. Ross2, M. Slifker2, D. Warshal3, J. Aikins3, R. Burger2. 1 Cooper University Hospital, Voorhees, NJ, 2Fox Chase Cancer Center, Philadelphia, PA, 3Cooper University Hospital, Camden, NJ. Objective: Bevacizumab has demonstrated therapeutic benefit in the front-line and recurrent disease setting for women with advanced Mullerian duct adenocarcinomas. Hypertension (HTN) is a well-known adverse effect observed with anti-VEGF agents such as bevacizumab. We hypothesized that early-onset hypertension requiring medical management could be predictive of treatment efficacy in this patient population. Methods: This historical cohort study included patients with endometrial, primary peritoneal, fallopian tube, and ovarian adenocarcinoma for whom bevacizumab was initiated between 2004 and 2010 at Fox Chase Cancer Center and Cooper University Hospital. The primary analysis was progression-free survival (PFS) by RECIST as a function of National Cancer Institute Common Toxicity Criteria version 3.0 grade ≥ 2 HTN developing or not developing within 8 weeks of treatment initiation. Secondary endpoints included overall survival (OS) and response rate (RR) by RECIST. Differences in PFS and OS between cohorts were evaluated using the logrank test and Cox proportional hazards regression, and differences in response rate were analyzed using the Fisher's exact test. Results: The study population consisted of 87 patients of whom 28 (32%) developed early-onset HTN. For the 50 patients with measurable disease, there was no significant difference in RR between the 15 who developed early HTN (RR = 53%) and those who did not (RR = 51%). In an unadjusted analysis, median PFS was 14.0 months for those who developed early HTN versus 7.7 months for those who did not (P = 0.0796). After adjusting for age and disease status (optimal stage III; suboptimal stage III & stage IV; recurrence-platinum sensitivity), patients who developed early HTN had a 55% reduction (p = 0.029, 95% CI = 8%, 78%), in the hazard of progression relative to patients who did not. In an unadjusted analysis, median OS was 17.6 months for those who developed early HTN versus 11 months for those that did not (P = 0.103). The adjusted analysis demonstrated that those with early HTN had a 66% reduction (p = 0.012; [95% CI =22%, 86%]) in the hazard of death relative to patients who did not. Conclusions: Our data suggest that after adjustments for important prognostic factors, PFS and OS are significantly prolonged for patients with