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Symptoms and adverse effects with chemotherapy ± bevacizumab for platinum-resistant recurrent ovarian cancer: Analysis of the phase III AURELIA trial
Abstracts / Gynecologic Oncology 130 (2013) e1–e169
with adjusting factors and other background factors, i.e., age, lesion site, platinum-free interval (PFI). Results: The median follow-up was 17.6 months. Median OS was 18.3 months in the TP group, 17.5 months in the TC group, and 18.0 months in both groups combined. The HR was 0.69 in patients with pretreatment hemoglobin levels higher than or equal to the median value (P = 0.016; 95% CI, 0.51–0.93), 2.23 in patients with a PFI b6 months (P = 0.001; 95% CI, 1.38–3.60), 1.60 in patients with a PFI ≥6 months to b12 months (P = 0.045; 95% CI, 1.01–2.53), and 1.83 in patients with a PS of 1 or higher (P b 0.001; 95% CI, 1.31–2.55). On the other hand, significant differences were not obtained for pretreatment platelet count or other factors. Conclusions: In addition to the known prognostic factors of PS, which was used as one of the adjusting factors, lower hemoglobin level and a PFI of b12 months were newly found to be associated with poor outcomes in patients with cervical cancer. These variables should, therefore, be considered as new adjusting factors in future clinical trials of similar patients. doi:10.1016/j.ygyno.2013.04.061
3 A phase II evaluation of carboplatin/paclitaxel/bevacizumab in the treatment of advanced stage endometrial carcinoma D. O’Malley, G. McCann, J. Fowler, L. Copeland, F. Backes, R. Salani, E. Eisenhauer, D. Cohn. The Ohio State University, Columbus, OH. Objective: To report the treatment efficacy of carboplatin, paclitaxel, and bevacizumab (C/T/Bev) in stage III/IV endometrial cancer patients who have undergone primary surgical treatment. Methods: On day 1, carboplatin (AUC 5), paclitaxel (175 mg/m2), and bevacizumab (15 mg/kg) was given every 21 days in single-arm open-label phase II for a maximum of 6 cycles in patients with or without measurable disease. Toxicity was reported using CTCAE v3 as maximum grade per pt. Thirty-eight pts were enrolled to assess whether the 24-month failure-free rate (FFR) (events defined as disease progression, death without progression, or discontinuation due to progression, death, or unacceptable toxicity) is at most 50% against the alternative that the 24-month FFR is at least 70% (alpha of 0.1, beta of 0.1, power of 90%). Patients without a defined event were censored at the last tumor assessment date. Results: Thirty-eight pts were evaluable (6 stage IIIA; 24 stage IIIC; 8 stage IVB). 31/38 (82%) completed the 6 cycles. Four pts were removed due to a significant adverse effect (fascia dehiscence, vaginal dehiscence, pulmonary embolism, neutropenic sepsis), and 21/38 (55%) experienced grade 3/4 neutropenia. Four of 38 (11%) pts experienced febrile neutropenia. There were no bowel perforations or fistulas. Median PFS was 26 months (mo) (range, 2-57 mo). Two pts are failure-free with less than 24 m of follow-up. 20/36 (55%) were failure-free at 24 mo. Conclusions: This is the first phase II trial to report efficacy with C/T/Bev in first-line advanced uterine cancer treatment. The regimen is relatively well- tolerated, with manageable acute toxicities. Evisceration (1 fascia, 1 vaginal) was seen in 2 pts, suggesting that consideration should be given to omitting Bev until cycle 2 in adjuvant uterine cancer trials. C/T/Bev had more than a 50% grade 3/4 neutropenia and 11% febrile neutropenia occurrence. C/T/Bev x 6 cycles failed to meet the primary objective of 70% FFR, although it is important to note that the 24-mo FFR in GOG 209 was approximately 40%. Future trials should consider including Bev maintenance following C/T/Bev in this high- risk population in an attempt to improve the FFR. doi:10.1016/j.ygyno.2013.04.062
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4 Symptoms and adverse effects with chemotherapy ± bevacizumab for platinum-resistant recurrent ovarian cancer: Analysis of the phase III AURELIA trial F. Hilpert1, M. Fabbro2, M. Jesus Rubio3, A. Reuss4, P. Rosenberg5, P. Benedetti Panici6, P. Vuylsteke7, P. Witteveen8, F. Zagouri9, E. Pujade-Lauraine10. 1AGO and University of Schleswig-Holstein Campus Kiel, Kiel, Germany, 2GINECO and CRLC Val d’Aurelle, Montpellier, France, 3 GEICO and Hospital Universitario Reina Sofia de Córdoba, Córdoba, Spain, 4 AGO and Universität Marburg, Marburg, Germany, 5NSGO and Linköping University Hospital, Linköping, Sweden, 6MITO and University of Rome “Sapienza”, Rome, Italy, 7BGOG and CMSE Namur, Namur, Belgium, 8DGOG and University Medical Center Utrecht, Utrecht, Netherlands, 9HECOG and General Peripheral Hospital of Athens “Alexandra”, Athens, Greece, 10 GINECO and Université Paris Descartes, Paris, France. Objective: The phase III AURELIA trial met its primary objective of improving progression-free survival (PFS) with the addition of bevacizumab (BEV) to chemotherapy (CT) for platinum-resistant ovarian cancer (OC) [Pujade- Lauraine, ASCO 2012]. The PFS hazard ratio was 0.48 (95% CI: 0.38 0.60; P b 0.001). Median PFS was 6.7 months with BEV-CT vs 3.4 months with CT. Overall response rates (RECIST and/or CA-125 criteria) were 30.9% and 12.6%, respectively (P b 0.001). We analyzed data for symptoms and adverse effects to describe clinical benefit:risk in AURELIA. Methods: Patients with platinum-resistant (progression b6 months after platinum-based therapy) measurable/assessable OC who had received 1-2 previous anticancer regimens were randomized to receive single-agent CT (investigator’s choice of paclitaxel, topotecan, or pegylated liposomal doxorubicin) alone or with BEV until disease progression or unacceptable toxicity. The primary endpoint was PFS; secondary endpoints included response, safety, and tolerability. Results: The median number of CT cycles was 6 in the BEV-CT arm vs 3 in the CT arm. Grade ≥3 adverse events (AEs) occurred in 58% vs 54% of patients. Hypertension, proteinuria (both typical of BEV), hand-foot syndrome, and peripheral sensory neuropathy were more common with BEV-CT than CT. However, grade ≥3 AEs associated with high tumor burden (abdominal pain, fatigue, dyspnea, vomiting) were consistently less frequent with BEV-CT than CT in each cycle. Conclusions: The significant improvement in PFS and response rate with the addition of BEV to CT is accompanied by a modest increase in treatment- related toxicities and improvement in AEs related to tumour burden. Additional exploratory analyses of symptoms over time will be presented doi:10.1016/j.ygyno.2013.04.063
5 Hyperthermic intraperitoneal chemotherapy following extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: Result of a prospective phase II study M. Lim, M. Im, H. Yoo, S. Seo, S. Kang, S. Park. National Cancer Center, Goyang-si, Republic of Korea. Objective: To investigate the pattern of failure and survival outcome associated with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with primary advanced epithelial ovarian cancer. Methods: Intraoperative HIPEC (cisplatin [75 mg/m2], 41.5 °C, 90 minutes) was performed in 30 patients with residual tumor b 1 cm after cytoreductive surgery between January 2007 and February 2008. All the patients received adjuvant chemotherapy with combination platinum and taxane.
with adjusting factors and other background factors, i.e., age, lesion site, platinum-free interval (PFI). Results: The median follow-up was 17.6 months. Median OS was 18.3 months in the TP group, 17.5 months in the TC group, and 18.0 months in both groups combined. The HR was 0.69 in patients with pretreatment hemoglobin levels higher than or equal to the median value (P = 0.016; 95% CI, 0.51–0.93), 2.23 in patients with a PFI b6 months (P = 0.001; 95% CI, 1.38–3.60), 1.60 in patients with a PFI ≥6 months to b12 months (P = 0.045; 95% CI, 1.01–2.53), and 1.83 in patients with a PS of 1 or higher (P b 0.001; 95% CI, 1.31–2.55). On the other hand, significant differences were not obtained for pretreatment platelet count or other factors. Conclusions: In addition to the known prognostic factors of PS, which was used as one of the adjusting factors, lower hemoglobin level and a PFI of b12 months were newly found to be associated with poor outcomes in patients with cervical cancer. These variables should, therefore, be considered as new adjusting factors in future clinical trials of similar patients. doi:10.1016/j.ygyno.2013.04.061
3 A phase II evaluation of carboplatin/paclitaxel/bevacizumab in the treatment of advanced stage endometrial carcinoma D. O’Malley, G. McCann, J. Fowler, L. Copeland, F. Backes, R. Salani, E. Eisenhauer, D. Cohn. The Ohio State University, Columbus, OH. Objective: To report the treatment efficacy of carboplatin, paclitaxel, and bevacizumab (C/T/Bev) in stage III/IV endometrial cancer patients who have undergone primary surgical treatment. Methods: On day 1, carboplatin (AUC 5), paclitaxel (175 mg/m2), and bevacizumab (15 mg/kg) was given every 21 days in single-arm open-label phase II for a maximum of 6 cycles in patients with or without measurable disease. Toxicity was reported using CTCAE v3 as maximum grade per pt. Thirty-eight pts were enrolled to assess whether the 24-month failure-free rate (FFR) (events defined as disease progression, death without progression, or discontinuation due to progression, death, or unacceptable toxicity) is at most 50% against the alternative that the 24-month FFR is at least 70% (alpha of 0.1, beta of 0.1, power of 90%). Patients without a defined event were censored at the last tumor assessment date. Results: Thirty-eight pts were evaluable (6 stage IIIA; 24 stage IIIC; 8 stage IVB). 31/38 (82%) completed the 6 cycles. Four pts were removed due to a significant adverse effect (fascia dehiscence, vaginal dehiscence, pulmonary embolism, neutropenic sepsis), and 21/38 (55%) experienced grade 3/4 neutropenia. Four of 38 (11%) pts experienced febrile neutropenia. There were no bowel perforations or fistulas. Median PFS was 26 months (mo) (range, 2-57 mo). Two pts are failure-free with less than 24 m of follow-up. 20/36 (55%) were failure-free at 24 mo. Conclusions: This is the first phase II trial to report efficacy with C/T/Bev in first-line advanced uterine cancer treatment. The regimen is relatively well- tolerated, with manageable acute toxicities. Evisceration (1 fascia, 1 vaginal) was seen in 2 pts, suggesting that consideration should be given to omitting Bev until cycle 2 in adjuvant uterine cancer trials. C/T/Bev had more than a 50% grade 3/4 neutropenia and 11% febrile neutropenia occurrence. C/T/Bev x 6 cycles failed to meet the primary objective of 70% FFR, although it is important to note that the 24-mo FFR in GOG 209 was approximately 40%. Future trials should consider including Bev maintenance following C/T/Bev in this high- risk population in an attempt to improve the FFR. doi:10.1016/j.ygyno.2013.04.062
e3
4 Symptoms and adverse effects with chemotherapy ± bevacizumab for platinum-resistant recurrent ovarian cancer: Analysis of the phase III AURELIA trial F. Hilpert1, M. Fabbro2, M. Jesus Rubio3, A. Reuss4, P. Rosenberg5, P. Benedetti Panici6, P. Vuylsteke7, P. Witteveen8, F. Zagouri9, E. Pujade-Lauraine10. 1AGO and University of Schleswig-Holstein Campus Kiel, Kiel, Germany, 2GINECO and CRLC Val d’Aurelle, Montpellier, France, 3 GEICO and Hospital Universitario Reina Sofia de Córdoba, Córdoba, Spain, 4 AGO and Universität Marburg, Marburg, Germany, 5NSGO and Linköping University Hospital, Linköping, Sweden, 6MITO and University of Rome “Sapienza”, Rome, Italy, 7BGOG and CMSE Namur, Namur, Belgium, 8DGOG and University Medical Center Utrecht, Utrecht, Netherlands, 9HECOG and General Peripheral Hospital of Athens “Alexandra”, Athens, Greece, 10 GINECO and Université Paris Descartes, Paris, France. Objective: The phase III AURELIA trial met its primary objective of improving progression-free survival (PFS) with the addition of bevacizumab (BEV) to chemotherapy (CT) for platinum-resistant ovarian cancer (OC) [Pujade- Lauraine, ASCO 2012]. The PFS hazard ratio was 0.48 (95% CI: 0.38 0.60; P b 0.001). Median PFS was 6.7 months with BEV-CT vs 3.4 months with CT. Overall response rates (RECIST and/or CA-125 criteria) were 30.9% and 12.6%, respectively (P b 0.001). We analyzed data for symptoms and adverse effects to describe clinical benefit:risk in AURELIA. Methods: Patients with platinum-resistant (progression b6 months after platinum-based therapy) measurable/assessable OC who had received 1-2 previous anticancer regimens were randomized to receive single-agent CT (investigator’s choice of paclitaxel, topotecan, or pegylated liposomal doxorubicin) alone or with BEV until disease progression or unacceptable toxicity. The primary endpoint was PFS; secondary endpoints included response, safety, and tolerability. Results: The median number of CT cycles was 6 in the BEV-CT arm vs 3 in the CT arm. Grade ≥3 adverse events (AEs) occurred in 58% vs 54% of patients. Hypertension, proteinuria (both typical of BEV), hand-foot syndrome, and peripheral sensory neuropathy were more common with BEV-CT than CT. However, grade ≥3 AEs associated with high tumor burden (abdominal pain, fatigue, dyspnea, vomiting) were consistently less frequent with BEV-CT than CT in each cycle. Conclusions: The significant improvement in PFS and response rate with the addition of BEV to CT is accompanied by a modest increase in treatment- related toxicities and improvement in AEs related to tumour burden. Additional exploratory analyses of symptoms over time will be presented doi:10.1016/j.ygyno.2013.04.063
5 Hyperthermic intraperitoneal chemotherapy following extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: Result of a prospective phase II study M. Lim, M. Im, H. Yoo, S. Seo, S. Kang, S. Park. National Cancer Center, Goyang-si, Republic of Korea. Objective: To investigate the pattern of failure and survival outcome associated with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with primary advanced epithelial ovarian cancer. Methods: Intraoperative HIPEC (cisplatin [75 mg/m2], 41.5 °C, 90 minutes) was performed in 30 patients with residual tumor b 1 cm after cytoreductive surgery between January 2007 and February 2008. All the patients received adjuvant chemotherapy with combination platinum and taxane.