Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994

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

Source: DOI: 10.1200/JCO.22.02852 Journal of Clinical Oncology 41, no. 32 (November 10, 2023) 5035-5043.

Dr. Anjan Patel's Thoughts

In the EORTC-55994 study, neoadjuvant chemotherapy followed by chemoradiation + surgery was not superior to chemoradiation for patients with stage IB2 – IIB cervical cancer. However, the toxicity was acceptable, so for patients with more locally advanced disease, it could be considered.

Regardless, the SOC will remain concurrent chemotherapy and radiation for these patients.

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

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