Why was GOG-0213 a negative trial?

Abstract

An ongoing question in the field of gynecologic oncology has been whether or not secondary cytoreductive surgery (SCS) followed by platinum-based chemotherapy increases overall survival (OS) in patients with platinum-sensitive recurrent ovarian cancer. Several retrospective studies have been published on this topic. Bristow et al. published a metaanalysis showing that complete cytoreductive surgery is the strongest independent factor for survival, demonstrating that with every 10% increase in complete cytoreduction, there was an associated 3 months' increase in median survival [1]. To this end, three large, multicenter, randomized, phase 3 trials-the DESKTOP III (NCT01166737), GOG-0213 (NCT00565851) and the SOC-1 trial (NCT01611766)-were designed to evaluate SCS followed by platinumbased chemotherapy in these patients.Findings from the DESKTOP III trial were recently presented and demonstrated an improved median OS benefit of 7.5 months in the SCS followed by chemotherapy group compared with the chemotherapy-alone group (53.7 vs. 46.2 months, respectively). Looking further into the data, complete macroscopic resection resulted in a median OS benefit of approximately 15 months (60.7 vs. 46.2 months, respectively) [2]. On the other hand, data from the GOG-0213 study did not show an improvement in median OS with SCS followed by chemotherapy compared with chemotherapy alone (50.6 vs. 64.7 months, respectively) [3]. Even when comparing only patients who achieved complete gross resection (CGR) to those who did not undergo SCS, there was still no median OS advantage (56.0 vs. 64.7 months, respectively) [3]. Both the GOG-0213 and DESKTOP III trials, however, did show a progression-free survival (PFS) benefit in the surgery versus no-surgery arms (18.9 versus 16.2 months in GOG-0213 and 18.4 versus 14.0 months in DESKTOP III, respectively) [2,3]. Median OS data from the SOC-1 trial are still immature; however, median PFS was 17.4 months in the surgery arm and 11.9 months in the no-surgery arm [4].These findings have left gynecologic oncologists wondering why the data from GOG-0213 did not show an OS benefit with SCS, as they did with DESKTOP III. We looked at similarities and differences in trial design and reported outcomes to address this question. Median platinum-free interval, which is a well-established, important prognostic factor for patients with recurrent disease, was similar between the 2 studies (20.4 months in GOG-0213 and 21.1 months in DESKTOP III) [2,3]. Patients in the SOC-1 trial, however, had a median platinum-free interval of 16 months, suggesting the trial enrolled more higher-risk

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA‐3001)

“…The GOG-213 trial has failed to show the superiority of surgery, whereas the AGO-DESKTOP III and SOC-1 trials have reported promising results for SCS in well-selected patients with platinum-sensitive recurrent ovarian cancer. [7][8][9]13 While there are several potential explanations for the contradictory results, 14 the most important among them may be the lack of standardized criteria for patient selection. In the GOG- Center.…”

Simplified Selection Criteria for Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer

“…There might be several reasons for these contradictory results. Among them, the most important factor may be the patient selection strategy [ 11 ]. In the GOG-213 trial, eligibility was based on the surgeons’ preferences, without uniform selection criteria across the participating centers.…”

Prediction Models for Complete Resection in Secondary Cytoreductive Surgery of Patients With Recurrent Ovarian Cancer

“…Data on OS are different in these two completed trials. With respect to the inconsistent results, a large amount of discussion focuses on issues such as platinum-free interval, pattern of recurrence, BRCA (breast cancer gene) status, and the use of bevacizumab and/or poly-ADP ribose polymerase (PARP) inhibitors ( 14 , 15 ). Recently, a meta-analysis encompassed the above three RCTs and showed that SCS was superior to chemotherapy alone in terms of PFS, and particularly with PFS and OS benefits in the CGR subpopulation ( 8 ).…”