OV21/PETROC : A randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer
Mené sur 275 patientes atteintes d'un cancer épithélial de l'ovaire de stade IIB-IVA et ayant subi une chimiothérapie néoadjuvante ainsi qu'une chirurgie de réduction tumorale, cet essai de phase II évalue, du point de vue du taux de progression de la maladie à 9 mois, l'intérêt d'une chimiothérapie intrapéritonéale par rapport à une chimiothérapie systémique
Background : The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and Methods : We performed a multicentre, 2 stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (IV) NACT followed by optimal (<1cm) debulking surgery were randomized to one of 3 treatment arms: 1) IV carboplatin/paclitaxel; 2) IP cisplatin plus IV/IP paclitaxel, or 3) IP carboplatin plus IV/IP paclitaxel. The primary endpoint was 9 month progressive disease rate (PD9). Secondary endpoints included progression free survival (PFS), overall survival (OS), toxicity and quality of life (QOL). Results : Between 2009 and 2015, 275 patients were randomized. IP cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared IV carboplatin/paclitaxel (n = 101) to IP carboplatin, IV/IP paclitaxel (n = 102). The intention to treat PD9 was lower in the IP carboplatin arm compared to the IV carboplatin arm: 24.5% (95% CI 16.2%-32.9%) vs. 38.6% (95% CI 29.1%- 48.1%) p = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57 - 1.17); p = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) p = 0.40. The IP carboplatin based regimen was well tolerated with no reduction in QOL or increase in toxicity compared to IV administration alone. Conclusion : In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, IP carboplatin based chemotherapy is well tolerated and associated with an improved PD9 compared to IV carboplatin based chemotherapy.
Annals of Oncology 2017