Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial.
Journal
Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R
Informations de publication
Date de publication:
25 02 2023
25 02 2023
Historique:
received:
21
05
2022
revised:
26
10
2022
accepted:
21
11
2022
pubmed:
5
2
2023
medline:
3
3
2023
entrez:
4
2
2023
Statut:
ppublish
Résumé
Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy. We performed a multicentre, randomised, double-blind, placebo-controlled trial across 50 UK hospitals. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m Between Nov 2, 2016, and Oct 6, 2021, 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). Three participants in the placebo group withdrew. Surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and in 47 (29%) of 160 participants in the placebo group (adjusted risk ratio 1·15, 95% CI 0·85 to 1·58; adjusted risk difference -0·01, 95% CI -0·10 to 0·09; p=0·37). Without surgical intervention, median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group (subdistribution hazard ratio 1·03, 95% CI 0·75 to 1·40). Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and in six (4%) of 162 participants in the placebo group. Diarrhoea and rash were more common in the gefitinib group. In women with a tubal ectopic pregnancy, adding oral gefitinib to parenteral methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions. National Institute of Health Research.
Sections du résumé
BACKGROUND
Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy.
METHODS
We performed a multicentre, randomised, double-blind, placebo-controlled trial across 50 UK hospitals. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m
FINDINGS
Between Nov 2, 2016, and Oct 6, 2021, 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). Three participants in the placebo group withdrew. Surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and in 47 (29%) of 160 participants in the placebo group (adjusted risk ratio 1·15, 95% CI 0·85 to 1·58; adjusted risk difference -0·01, 95% CI -0·10 to 0·09; p=0·37). Without surgical intervention, median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group (subdistribution hazard ratio 1·03, 95% CI 0·75 to 1·40). Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and in six (4%) of 162 participants in the placebo group. Diarrhoea and rash were more common in the gefitinib group.
INTERPRETATION
In women with a tubal ectopic pregnancy, adding oral gefitinib to parenteral methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions.
FUNDING
National Institute of Health Research.
Identifiants
pubmed: 36738759
pii: S0140-6736(22)02478-3
doi: 10.1016/S0140-6736(22)02478-3
pii:
doi:
Substances chimiques
Methotrexate
YL5FZ2Y5U1
Gefitinib
S65743JHBS
Types de publication
Randomized Controlled Trial
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
655-663Subventions
Organisme : Medical Research Council
ID : G0802808
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16003
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : PCL/19/01
Pays : United Kingdom
Investigateurs
Amna Ahmed
(A)
Hazel Alexander
(H)
Sonal Anderson
(S)
Rita Arya
(R)
Gabriel Awadzi
(G)
Miriam Baumgarten
(M)
Renee Behrens
(R)
Kelly Bingham
(K)
Cecilia Bottomley
(C)
Tom Bourne
(T)
Ying Cheong
(Y)
Justin Chu
(J)
Frances Collins
(F)
Janet Cresswell
(J)
Sangeetha Devarajan
(S)
Punukollu Durgadevi
(P)
Umo Esen
(U)
Radwan Faraj
(R)
Priscilla Fernandez
(P)
Joanne Fletcher
(J)
Benjamin Galea
(B)
Ingrid Granne
(I)
Pratima Gupta
(P)
Susannah Hogg
(S)
Shahzya Huda
(S)
Sucheta Iyengar
(S)
Ngozi Izuwah-Njoku
(N)
Feras Izzat
(F)
Thangamma Katimada-Annaiah
(T)
Pinky Khatri
(P)
Kathleen King
(K)
Emma Kirk
(E)
Chitra Kumar
(C)
Geeta Kumar
(G)
Louise Linsell
(L)
Mayank Madhra
(M)
Krupa Madhvani
(K)
Rebecca McKay
(R)
Fouzia Memon
(F)
Usha Menon
(U)
Shruti Mohan
(S)
Scott Nelson
(S)
Helena Nik
(H)
Hema Nosib
(H)
Jerry Oghoetuoma
(J)
Abigail Oliver
(A)
Binita Pande
(B)
Mamta Pathak
(M)
Alexandra Peace-Gadsby
(A)
Janaki Putran
(J)
Sundararajah Raajkumar
(S)
Vinita Raheja
(V)
Malar Raja
(M)
Gautam Raje
(G)
Sandhya Rao
(S)
Penny Robshaw
(P)
Faye Rodger
(F)
Jackie Ross
(J)
Sherif Saleh
(S)
Sridevi Sankharan
(S)
Mona Sharma
(M)
Sanjay Sinha
(S)
Kate Stewart
(K)
Lauren Sutherland
(L)
Rebecca Thompson
(R)
Sakunthala Tirumuru
(S)
Nicola Watson
(N)
Sandra Watson
(S)
Ursula Winters
(U)
Catherine Wykes
(C)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 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 AWH has received funding from Roche Diagnostics, and honoraria for consultancy for Ferring, Roche, Nordic Pharma, AbbVie, Benevolent AI, and GSK. ST is named on patents relating to use of epidermal growth factor receptor inhibitors to treat ectopic pregnancy and is on an advisory board for the Menzies Medical Research Institute. WCD has received honoraria from Merck and Guerbet and research funding from Galvani Biosciences. BWM reports consultancy for ObsEva and Merck and travel support from Merck. LHRW has received grant funding from National Institute of Health Research (NIHR) Health Technology Assessment (HTA) and Roche Diagnostics. TH has received honoraria from Olympus for teaching. All other authors declare no competing interests.