Author(s): Gemma G. Kenter, MD, PhD1; Stefano Greggi, MD, PhD2; Ignace Vergote, MD, PhD3; Dionyssios Katsaros, MD, PhD4; Juliusz Kobierski, MD5; Heleen van Doorn, MD, PhD6; Fabio Landoni, MD, PhD7; Jacobus van der Velden, MD, PhD8; Nicholas Reed, MD, PhD9; Corneel Coens, PhD10; Iske van Luijk, MD11; Nicoletta Colombo, MD, PhD12; Elzbietta van der Steen-Banasik, MD, PhD13; Nelleke Ottevanger, MD, PhD14; and Antonio Casado, MD, PhD15; on behalf of the EORTC-55994 Study Group
PURPOSE
This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma.
METHODS
Between May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL).
RESULTS
After a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) ≥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs ≥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80).
CONCLUSION
This trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.
Author Affiliations
1Center for Gynaecologic Oncology Amsterdam, Amsterdam University Medical Center, Netherlands Cancer Institute, Amsterdam, the Netherlands; 2Gynaecologic Oncology, Istituto Nazionale Tumori di Napoli IRCCS “Fondazione G. Pascale”, Naples, Italy; 3Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; 4Department of Surgical Sciences, AOU Citta della Salute, Gynecologic Oncology, PO SANNA, University of Torino, Torino, Italy; 5Department of Gynecology and Gynecologic Oncology, Medical University of Gdansk, Gdansk, Poland; 6ErasmusMC Cancer Institute, University Medical Center, Rotterdam, the Netherlands; 7Gynecologic Clinic Milano Bicocca University, Ospedale San Gerardo, Monza, Italy; 8Amsterdam University Medical Center, Amsterdam, the Netherlands; 9Medical Oncology, Gartnavel General Hospital, Glasgow, United Kingdom; 10European Organization on Research and Treatment of Cancer Headquarters, Brussels, Belgium; 11Haaglanden Medical Center, The Hague, the Netherlands; 12European Institute of Oncology, Milano, Italy; 13Radiotherapiegroep Arnhem, Amsterdam, the Netherlands; 14Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; 15Medical Oncology, University Hospital San Carlos, Madrid, Spain
