Long Term Survival of GOG 252 ‘Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/GOG Study’ (021)

Abstract

<b>Objectives:</b> The primary objective of this analysis of GOG 252 is to assess the overall survival of the subgroup of participants with metastatic epithelial ovarian cancer, with no more than microscopic residual disease, following their primary cytoreductive surgery followed by three chemotherapy regimens and bevacizumab. The results of the response to chemotherapy based on the CA-125 nadir are also included. <b>Methods:</b> Patients were randomly assigned to six cycles of IV paclitaxel 80 mg/m2 weekly, with IV carboplatin AUC 6 on day 1 (IV carbo arm), versus IV paclitaxel 80 mg/m2 weekly, with IP carboplatin AUC 6 on day 1 (IP carbo arm) versus IV paclitaxel 135 mg/m2 IV on day 1 every three weeks, IP cisplatin 75 mg/m2 on day 2, and IP paclitaxel 60 mg/m2 on day 8 (IP Cisplatin arm). All participants received bevacizumab 15 mg/kg IV on day 1 every three weeks for cycles 2-22. CA-125 was drawn before each cycle of chemotherapy, and q3 months for the first two years and q6 months for the next three years and then annually. CT was performed postoperatively and before enrollment, and then every six months for five years and then annually. <b>Results:</b> A total of 1560 patients were enrolled of whom 900 (57.7%) had no more than microscopic residual disease as assessed by the surgeon. For this analysis, an excellent response to front line chemotherapy was to see a nadir of CA-125 < 10 before cycle 4. The median duration of follow up was 9.2 years. There were 573 with recurrent disease (63.7%) and 413 deaths (45.9%). There was no statistically significant difference in PFS between treatment groups (p=0.735, log-rank Chi square=0.617 with 2 DF). The hazard of progression or death is relatively high for the first 3-4 years and then declines. The estimates of proportion of patients alive and recurrence-free at 10 years were 0.32, 0.33, and 0.32, respectively. The probability of living at least 10 years was 0.473, 0.467 and 0.470. The CA-125 nadir after cycle 1 and before cycle 4 of less than 10 was 53.5% 51.5%, and 34.4% in the three arms, respectively. The median PFS was 28.5 months for those with CA-125 nadir > 10 IU and 44.2 months for those less than or equal to 10 IU. The median survival for CA-125 nadir greater than 10 was 89 months. <b>Conclusions:</b> The overall survival of these patients was remarkable and was 108.6, 114.2, and 107.9 months, respectively. The proportional hazard model stratified by stage indicates the hazard of death is 38.5% higher among those with nadir values of CA-125 > 10. The quality of life was best in the intravenous arm.Fig. 1