- Email: [email protected]
CA125 surveillance and second-line intraperitoneal platinum-based therapy increases second line progression-free survival for epithelial ovarian cancer
S110
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
261 CA125 surveillance and second-line intraperitoneal platinumbased therapy increases second line progression-free survival for epithelial ovarian cancer M. Boisen1, J. Lesnock1, W. McBee2, S. Richard1, J. Kelley1, K. Zorn1, T. Krivak1, R. Edwards1. 1Magee Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, 2Heiskell, King, Burns and Tallman Surgical Associates, Morgantown, WV. Objective: Previous studies have suggested that only 3% of patients with epithelial ovarian cancer (EOC) have a longer progression-free survival (PFS) after second-line intravenous (IV) platinum chemotherapy than with front-line IV therapy (Markman, 2004). We examined what impact second-line intraperitoneal (IP) platinum might have on the ratio of second-line to first-line PFS in patients treated with IP platinum chemotherapy for first recurrence after front-line IV therapy. Methods: A retrospective, descriptive, single-institution analysis of women who received IP chemotherapy for recurrent EOC between January 2005 and March 2011 was conducted. Study patients were identified from the tumor registry and office records from a large Gynecologic Oncology practice. The records were reviewed for demographic factors including age, ethnicity, primary tumor histology, stage, grade, and the cytoreduction volume after primary and secondary surgeries. The first and second PFSs were defined as the time from the end of previous platinum-based therapy to the start of next the therapy. Results: Fifty-nine women received IP chemotherapy for their first EOC recurrence after IV chemotherapy. The mean age was 56 years (range 43–79). All patients had previously undergone primary surgical cytoreduction (80% optimally cytoreduced) followed by IV platinum-based chemotherapy. All patients underwent biopsy, and when necessary cytoreduction at the time of IP port placement. Because many of these women were identified by rising CA125 with small volume recurrent disease (mean CA125 133 IU/ml, range 4– 792), few women required extensive surgery. The majority (70%) of patients were considered optimal (b1 cm residual disease) at the completion of their second surgery. In 15 patients (25%) we observed longer PFS after IP chemotherapy than after primary IV chemotherapy. In this patient population, 85% had papillary serous histology of primary tumor; other histologies include clear cell, endometrioid, and carcinosarcoma. For these 15 patients, the median PFS for primary response was 8 months (range 5–56), while median PFS after IP chemotherapy for recurrent disease was 24 months (range 10–75). Conclusions: For EOC patients with limited peritoneal recurrence, there appears to be a significant increase in the number that can be expected to have their second-line IP-platinum PFS exceed their firstline IV-platinum PFS as compared to published data with IV therapy for recurrence. doi:10.1016/j.ygyno.2011.12.262
262 Downstream effects of first line bevacizumab (bev) on outcomes after recurrence in advanced ovarian cancer E. Bishop1, L. Perry1, R. Previs2, A. Alvarez-Secord2, K. Moore1. 1 University of Oklahoma, Oklahoma City, OK, 2Duke University Medical Center, Durham, NC. Objective: Bevacizumab has been shown to improve PFS in advanced epithelial ovarian cancer (OC), but long term effects of incorporating bev into first-line treatment remains controversial. The goal of this study was to assess the prognostic effect of first-line bev on response at the time of treatment for recurrence in advanced OC. Methods: Retrospective data was collected for 160 pts from 2 institutions from 2001 to 2010. All pts had stage II–IV OC, underwent
primary surgical cytoreduction (CRS), received platinum based chemotherapy (CT) with or without bev, and have developed recurrent disease. Pts were stratified based on bev exposure and on response to, and PFS following, 2nd line chemotherapy (CT2). The primary endpoint was 2nd progression free interval (PFI2) defined as time from starting CT2 until start of third line CT, or date of last follow up for those who did not have a 2nd recurrence. Univariate and multivariate analysis identified prognostic factors for PFI2. Secondary endpoint was evidence of clinical benefit (CB) defined as complete or partial response to CT2 or stable disease. Results: Of the 160 pts, 25% received first-line bev (bev + platinum and/or bev maintenance) while the remainder received platinumbased CT. Following CRS 66% had b1 cm residual disease. 70% of pts were platinum sensitive. Following 2nd line therapy, 16% remain disease free, and 84% had a 2nd disease recurrence. With a median follow up of 38 months, mean primary PFI after initial platinum based therapy was 17.4 months and mean PFI2 was 10.6 months. In pts with platinum sensitive recurrent disease, there was no difference seen in mean PFI2 between pts who received first line bev and those who did not (8 vs. 7 months). Multivariate analysis of prognostic factors for response to CT2 included residual disease following CRS, CT2 agent, and front line bev use. Primary bev exposure was an independent predictor of CB during CT2 (p = 0.007). This improvement in CB was not seen in the platinum resistant subset of pts and similarly, there was no difference in PFI2 (5 vs. 5 months). Conclusions: These results suggest that advanced OC pts treated with first line bev do not have worse response to therapy for recurrent disease than pts treated with platinum-based CT. In fact, in pts with platinum sensitive OC, treatment with first line bev may actually result in improved clinical benefit following therapy for recurrent disease. If these results are confirmed, this raises the question of the true effect of bev on tumor microenvironment. doi:10.1016/j.ygyno.2011.12.263
263 Annual cost of bevacizumab in the adjuvant treatment of ovarian cancer to the U.S. Medicare system A. Walter, J. Geisler, K. Manahan. University of Toledo Medical Center, Toledo, OH. Objective: To determine the potential annual cost of adding bevacizumab to the adjuvant treatment of ovarian cancer (EOC). Methods: A decision model was developed based on Gynecologic Oncology Group (GOG) protocol 218. Arm 1 is 6 cycles of carboplatin/ paclitaxel (CP). Arm 2 is 1 cycle of CP, 5 cycles of CP + bevacizumab (B), and 16 cycles of B alone (CPB + B). Actual and estimated costs of treatment plus the potential costs of complications based on Medicare reimbursement and published data were established for each regimen. An acceptable willingness to pay was considered $50,000 per person per life year gained. Results: Of the nearly 22,000 women who will develop EOC yearly, approximately 85% (18,598) will need chemotherapy after surgery. The cost of chemotherapy agents and infusion of them was $3,138.72/ person for CP and $190,630.47/person for CPB + B. Annual cost to the U.S. economy for infusion of medications alone would be $27 million versus for CP versus N$13.5 billion dollars for CPB + B, respectively. If cost per quality adjusted progression free life year (PFLY) is examined per person, it would be $14,656/PFLY versus $184,306/PFLY giving an incremental cost effectiveness ration (ICER) of $727,183/PFLY. This is well above an accepted level of $50,000 per life year gained. Thus, to increase on average 1 year of PFL (not survival) for each woman with EOC, the U.S. healthcare expenditure would have to increase spending on EOC alone by N$13 billion.
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
261 CA125 surveillance and second-line intraperitoneal platinumbased therapy increases second line progression-free survival for epithelial ovarian cancer M. Boisen1, J. Lesnock1, W. McBee2, S. Richard1, J. Kelley1, K. Zorn1, T. Krivak1, R. Edwards1. 1Magee Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, 2Heiskell, King, Burns and Tallman Surgical Associates, Morgantown, WV. Objective: Previous studies have suggested that only 3% of patients with epithelial ovarian cancer (EOC) have a longer progression-free survival (PFS) after second-line intravenous (IV) platinum chemotherapy than with front-line IV therapy (Markman, 2004). We examined what impact second-line intraperitoneal (IP) platinum might have on the ratio of second-line to first-line PFS in patients treated with IP platinum chemotherapy for first recurrence after front-line IV therapy. Methods: A retrospective, descriptive, single-institution analysis of women who received IP chemotherapy for recurrent EOC between January 2005 and March 2011 was conducted. Study patients were identified from the tumor registry and office records from a large Gynecologic Oncology practice. The records were reviewed for demographic factors including age, ethnicity, primary tumor histology, stage, grade, and the cytoreduction volume after primary and secondary surgeries. The first and second PFSs were defined as the time from the end of previous platinum-based therapy to the start of next the therapy. Results: Fifty-nine women received IP chemotherapy for their first EOC recurrence after IV chemotherapy. The mean age was 56 years (range 43–79). All patients had previously undergone primary surgical cytoreduction (80% optimally cytoreduced) followed by IV platinum-based chemotherapy. All patients underwent biopsy, and when necessary cytoreduction at the time of IP port placement. Because many of these women were identified by rising CA125 with small volume recurrent disease (mean CA125 133 IU/ml, range 4– 792), few women required extensive surgery. The majority (70%) of patients were considered optimal (b1 cm residual disease) at the completion of their second surgery. In 15 patients (25%) we observed longer PFS after IP chemotherapy than after primary IV chemotherapy. In this patient population, 85% had papillary serous histology of primary tumor; other histologies include clear cell, endometrioid, and carcinosarcoma. For these 15 patients, the median PFS for primary response was 8 months (range 5–56), while median PFS after IP chemotherapy for recurrent disease was 24 months (range 10–75). Conclusions: For EOC patients with limited peritoneal recurrence, there appears to be a significant increase in the number that can be expected to have their second-line IP-platinum PFS exceed their firstline IV-platinum PFS as compared to published data with IV therapy for recurrence. doi:10.1016/j.ygyno.2011.12.262
262 Downstream effects of first line bevacizumab (bev) on outcomes after recurrence in advanced ovarian cancer E. Bishop1, L. Perry1, R. Previs2, A. Alvarez-Secord2, K. Moore1. 1 University of Oklahoma, Oklahoma City, OK, 2Duke University Medical Center, Durham, NC. Objective: Bevacizumab has been shown to improve PFS in advanced epithelial ovarian cancer (OC), but long term effects of incorporating bev into first-line treatment remains controversial. The goal of this study was to assess the prognostic effect of first-line bev on response at the time of treatment for recurrence in advanced OC. Methods: Retrospective data was collected for 160 pts from 2 institutions from 2001 to 2010. All pts had stage II–IV OC, underwent
primary surgical cytoreduction (CRS), received platinum based chemotherapy (CT) with or without bev, and have developed recurrent disease. Pts were stratified based on bev exposure and on response to, and PFS following, 2nd line chemotherapy (CT2). The primary endpoint was 2nd progression free interval (PFI2) defined as time from starting CT2 until start of third line CT, or date of last follow up for those who did not have a 2nd recurrence. Univariate and multivariate analysis identified prognostic factors for PFI2. Secondary endpoint was evidence of clinical benefit (CB) defined as complete or partial response to CT2 or stable disease. Results: Of the 160 pts, 25% received first-line bev (bev + platinum and/or bev maintenance) while the remainder received platinumbased CT. Following CRS 66% had b1 cm residual disease. 70% of pts were platinum sensitive. Following 2nd line therapy, 16% remain disease free, and 84% had a 2nd disease recurrence. With a median follow up of 38 months, mean primary PFI after initial platinum based therapy was 17.4 months and mean PFI2 was 10.6 months. In pts with platinum sensitive recurrent disease, there was no difference seen in mean PFI2 between pts who received first line bev and those who did not (8 vs. 7 months). Multivariate analysis of prognostic factors for response to CT2 included residual disease following CRS, CT2 agent, and front line bev use. Primary bev exposure was an independent predictor of CB during CT2 (p = 0.007). This improvement in CB was not seen in the platinum resistant subset of pts and similarly, there was no difference in PFI2 (5 vs. 5 months). Conclusions: These results suggest that advanced OC pts treated with first line bev do not have worse response to therapy for recurrent disease than pts treated with platinum-based CT. In fact, in pts with platinum sensitive OC, treatment with first line bev may actually result in improved clinical benefit following therapy for recurrent disease. If these results are confirmed, this raises the question of the true effect of bev on tumor microenvironment. doi:10.1016/j.ygyno.2011.12.263
263 Annual cost of bevacizumab in the adjuvant treatment of ovarian cancer to the U.S. Medicare system A. Walter, J. Geisler, K. Manahan. University of Toledo Medical Center, Toledo, OH. Objective: To determine the potential annual cost of adding bevacizumab to the adjuvant treatment of ovarian cancer (EOC). Methods: A decision model was developed based on Gynecologic Oncology Group (GOG) protocol 218. Arm 1 is 6 cycles of carboplatin/ paclitaxel (CP). Arm 2 is 1 cycle of CP, 5 cycles of CP + bevacizumab (B), and 16 cycles of B alone (CPB + B). Actual and estimated costs of treatment plus the potential costs of complications based on Medicare reimbursement and published data were established for each regimen. An acceptable willingness to pay was considered $50,000 per person per life year gained. Results: Of the nearly 22,000 women who will develop EOC yearly, approximately 85% (18,598) will need chemotherapy after surgery. The cost of chemotherapy agents and infusion of them was $3,138.72/ person for CP and $190,630.47/person for CPB + B. Annual cost to the U.S. economy for infusion of medications alone would be $27 million versus for CP versus N$13.5 billion dollars for CPB + B, respectively. If cost per quality adjusted progression free life year (PFLY) is examined per person, it would be $14,656/PFLY versus $184,306/PFLY giving an incremental cost effectiveness ration (ICER) of $727,183/PFLY. This is well above an accepted level of $50,000 per life year gained. Thus, to increase on average 1 year of PFL (not survival) for each woman with EOC, the U.S. healthcare expenditure would have to increase spending on EOC alone by N$13 billion.