Regorafenib or Tamoxifen for platinum-sensitive recurrent ovarian cancer with rising CA125 and no evidence of clinical or RECIST progression: A GINECO randomized phase II trial (REGOVAR).

To evaluate the efficacy and safety of regorafenib versus tamoxifen in platinum-sensitive ovarian cancer biological recurrence, defined by CA-125 increase without radiological (RECIST criteria) or symptomatic evidence of progression. 116 patients with platinum-sensitive ovarian cancer presenting an isolated increase of CA-125 were planned to be randomized. Regorafenib was administered orally at 160 or 120 mg daily, 3 weeks on/1 week off or tamoxifen at 40 mg daily, until disease progression or development of unacceptable toxicity. The primary endpoint was Progression-Free Survival, assessed by progression according to RECIST 1.1 or death (by any cause). Secondary endpoints included Overall Survival, Best Response and CA-125 response rate. 68 patients were randomized. Median age was 67 years (range: 30-87). Primary site of cancer was ovarian for most patients (92.6%). Tumors were predominantly serous / (89.7%), high grade (83.6%) and initial FIGO staging was III for 69.6% of the patients. Most (79.4%) patients were included after the first line of platinum-based treatment. After a median follow-up of 32 months, there was no difference of progression-free survival (PFS) between regorafenib and tamoxifen groups (p = 0.72), with median PFS of 5.6 months (CI 90%: 3.84-7.52) for the tamoxifen arm and 4.6 months (CI 90%: 3.65-7.33) for the regorafenib arm. There was also no difference in term of overall survival, best response or CA-125 response, delay to next therapy. Regorafenib presented a less favorable safety profile than tamoxifen, with grade 3/4 events occurring for 90.9% of the patients compared to 54.3% for tamoxifen. The most frequent were cutaneous, digestive, and biological events. Notably, hand-foot syndrome occurred in 36.4% of these patients. Regorafenib presented an unfavorable toxicity profile compared to tamoxifen, with no superior efficacy in this population of patients.

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. Trédan reports supports from the present manuscripts to ARCAGY GINECO from Bayer HealthCare, grants or contracts from Roche, BMS and MSD-Merck (payments to his institution), consulting fees from Roche, Pfizer, Astra-Zeneca, Lilly, Novartis-Sandoz, Daiichi-Sankyo, Seagen Pierre Fabre, MSD-Merck, Eisai (payments to him), payments/honoraria from Roche, Pfizer, Astra-Zeneca, Lilly, Novartis-Sandoz, Daiichi-Sankyo, Seagen, Pierre Fabre, MSD-Merck, Eisai, support for attending meeting and/or travel from Roche, Astra-Zeneca, Pfizer (payments to him). Dr. Hardy-Bessard reports payment/honoraria from MSD, Astra-Zeneca, GSK and participation on data safety monitoring board/advisory board with Clovis, MSD, Astra-Zeneca, GSK, Novartis, Pfizer. Dr. Lortholary reports payment/honoraria from Astra-Zeneca, Roche, MSD, Clovis, Novartis, support for attending meetings/travel from Roche and Astra-Zeneca and participation in a Data Safety Monitoring Board/Advisory board with Astra-Zeneca, Roche, MSD, Clovis and Novartis. Dr. Frenel reports payments/honoraria from Astra Zeneca, Lilly, Daiichi, Pfizer, Amgen, support for attending meetings/travel from Pfizer and Astra Zeneca, and participation on a Data Safety Monitoring Board/advisory board from Pfizer, Lilly, Novartis, GSK, Astra-Zeneca, MSD, Roche and Clovis. Dr. Louvet reports payments/honoraria from Merck, Roche, Servier and Amgen and support for attending meetings/travels from Roche and Merck. Dr. You reports consulting fees from MSD, Astra-Zeneca, GSK, Bayer, Roche, ECS Progastrine, Novartis, LEK, Amgen, Clovis, Merck Serono, BMS, Seagen. Amélie Anota reports consulting fees from Roche, Astra-Zeneca, Sandoz, Pfizer/Hospira, payment or honoraria for lectures from Astra-Zeneca and BMS and support for attending meetings/travels from Roche, Astra-Zeneca and Novartis. Pr Ray-Coquard reports consulting fees from Amgen, Astra-Zeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, Pfizer/Merck-Sereno, PharmaMar, and Roche, grants/contracts with Roche, BMS, MSD, GSK Company and support for attending meetings/travels from Astra-Zeneca, Roche, GSK and Clovis. The remaining authors declare no conflict of interest.