Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial.

BACKGROUND

Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival.

METHODS

The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m

FINDINGS

Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group.

INTERPRETATION

Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer.

FUNDING

Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests GE reports consulting fees from MSD and Eisai; payment or honoraria from Eisai and GSK; support for attending meeting from MSD; and participation on Data Safety Monitoring Board or Advisory Board for GSK, MSD, and Eisai, outside the submitted work. JAL reports grants from AstraZeneca and Merck/MSD; consulting fees from AstraZeneca, Clovis Oncology, GSK, Artios Pharma, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Immagene, Incyte, Immunogen/AbbVie, and Novocure; payment or honoraria from AstraZeneca, MSD/Merck, Clovis Oncology, and GSK; participation on Data Safety Monitoring Board or Advisory Board for Mersana and SutroBio; and leadership role on the European Society for Medical Oncology's Clinical Practice Guidelines—Gynaecological Cancer—until December, 2023, past Vice President role for the European Society of Gynaecological Oncology, until 2021, and Chair for National Ovarian Cancer Audit Committee, outside the submitted work. MM reports payment or honoraria from MSD, Eisai, GSK, Roche, and Medscape; support for attending meetings or travel from Daiichi Sanko; and past role as a Chair of Cervical Cancer Research Network (until September 2021), outside the submitted work. AM reports participation on data safety monitoring board or advisory board for Cannariabio (on an ovarian cancer trial, since 2023) and executive committee member role with the Gynecologic Cancer Intergroup (since 2024), outside the submitted work. AH reports honoraria for educational activities from AbbVie, Almirall, Boehringer Ingelheim, Clovis Oncology, Ipsen, Takeda, AstraZeneca, Daiichi Sankyo, Merck Serono, MSD, UCB, Kyowa Kirin, Servier, Sobi, Pfizer, and Roche, outside the submitted work. All other authors declare no competing interests.