( SGO ) A phase III trial of bevacizumab with IV versus IP chemotherapy for ovarian, fallopian tube, and peritoneal carcinoma: An NRG Oncology Study Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

SGO conference
Monday, March 21, 2016 03:13 PM - 03:20 PM

Conclusions
•All arms have excessive toxicity
•Neurotoxicity is similarly high in all arms
•Reserve changes in treatment recommendations until survival data available for no residual disease high grade serous Stage III participants.
•IP Cisplatin increases bevacizumab associated HTN (hypertension)

Discussion
•Survival for optimal and no residual disease participants will not be available for a few years.
•Dose reductions of paclitaxel and cisplatin as well as cross-over may have compromised efficacy.
•Dose dense paclitaxel may have improved efficacy to allow us to abandon IP chemo-must we wait-combine both?
•Bevacizumab interactions could have clouded analysis

Objectives: To determine if one or both intraperitoneal chemotherapy (IP) regimens improves the progression-free survival (PFS) compared to intravenous (IV) chemotherapy for first-line treatment of patients diagnosed with optimally surgically resected stage II and III ovarian, peritoneal, or fallopian tube cancer. Methods: Eligible patients had stage II-IV epithelial ovarian, peritoneal, or fallopian tube carcinoma. They were treated with bevacizumab 15mg/kg IV on cycles 2-22, and randomized to receive six cycles of: Arm 1) IV carboplatin AUC 6/ IV weekly paclitaxel 80 mg/m2 (IV arm) or Arm 2) IP carboplatin AUC 6/ IV weekly paclitaxel 80 mg/m2/ (IP-carbo arm) or Arm 3) IV paclitaxel 135 mg/m2 day 1/IP cisplatin 75 mg/m2 day 2/IP paclitaxel 60 mg/m2 day 8 (IP-cis arm).
Results: Among, 1,560 trial participants, the median age was 58 years. 84% had Stage III disease, 72% had high grade serous histology, 57% had no visible residual disease following optimal cytoreduction. Completion rates of platinum, taxane, or bevacizumab appear in the Table. Cross-over to the IV only therapy occurred in 16% randomized to IP carbo arm and 28% randomized to IP cis arm.

Treatment Arm	At least 6 cycles of Platinum	At least 6 cycles of Taxane	Median # bev cycles
IV only	90%	87%	20
IP carbo	91%	88%	18
IP cis	84%	87%	17

15 deaths possibly due to toxicity were relatively evenly distributed among treatment arms. Similarly, GI perforations/fistula/leak occurred in all three arms (range, 3.7% - 5.3%). While nearly 30% of patients in each arm reported grade 2+ peripheral neuropathy, treatment-induced HTN (20.5%) and grade 3/4 nausea and vomiting (11.2%) were observed more often in the IP cis arm. IP therapy did not confer a significant PFS advantage over IV only, with the median PFS by intent-to-treat being 24.9 (IV), 27.3 (IP carbo), and 26.0 mos (IP cis). Median PFS for Stage II/III patients with 1 cm or less visible tumor was 26.8 (IV), 28.7 (IP carbo), and 27.8 mos (IP cis). Median PFS for stage III patients with no visible residual disease was 31.3, 31.8, and 33.8 months respectively. No statistically significant PFS benefit for IP was identified.
Conclusions: The progression free survival was not improved with IP chemotherapy. IV and IP carbo arms using weekly dose-dense paclitaxel were better tolerated than the IP cis arm. Neurotoxicity is a major problem on all arms. The reduced dose IP cisplatin regimen does not appear to be as effective as previously reported high dose cisplatin regimens. Survival data is not yet mature.