Efficacy and safety results from GEICO 1205, a randomized phase II trial of neoadjuvant chemotherapy with or without bevacizumab for advanced epithelial ovarian cancer

Abstract

BackgroundBevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery.ObjectiveTo evaluate neoadjuvant bevacizumab in a randomized phase II trial.MethodsPatients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery.ResultsOf 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery.ConclusionsAdding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study

“…Adverse events were as expected and no new safety signals emerged, despite administration of neoadjuvant bevacizumab in 36% of patients. This finding is consistent with published safety results from the GEICO 1205 and ANTHALYA randomized phase II trials evaluating neoadjuvant bevacizumab; neither identified any particular safety concerns with neoadjuvant administration of bevacizumab 10 11. Hypertension and thromboembolic events were slightly more common in older than younger patients; this finding is consistent with the known increased risk of these events in older patients and those with pre-existing hypertension, irrespective of treatment, and is also consistent with findings from the ROSiA study 12…”

Risk of Thrombo-Embolic Events in Ovarian Cancer: Does Bevacizumab Tilt the Scale? A Systematic Review and Meta-Analysis

“…In all, 71 articles underwent full-text review, of which 14 were available for inclusion for a total of 6119 patients (range 50–1873). Six studies were conducted in a frontline setting [ 16 , 17 , 33 , 34 , 35 , 36 ], 6 trials included patients with relapsed platinum-sensitive OC [ 20 , 21 , 37 , 38 , 39 , 40 ] and 2 with platinum-resistant OC [ 22 , 41 ]. The characteristics of all trials in the qualitative analysis are provided in Table 1 .…”

Management of advanced ovarian cancer in Spain: an expert Delphi consensus

“…The benefit of bevacizumab in stage III patients without residual disease has yet to be demonstrated, despite the results of an exploratory subgroup analysis of the ICON7 trial showing that the addition of bevacizumab to front-line chemotherapy improves PFS regardless of the stage or presence of residual disease [20]. The results of two randomized phase II trials did not show clear advantage for adding bevacizumab to neoadjuvant chemotherapy [21,22]. However, the administration of bevacizumab after IDS might provide a benefit regardless of whether complete cytoreduction is achieved, as these patients are at higher risk of relapse due to greater tumor burden at diagnosis precluding PDS).…”