Oral Gefitinib and methotrexate combo has no clinical advantage over methotrexate for tubal ectopic pregnancy

A new study found that combining oral gefitinib with parenteral methotrexate has no clinical advantage over methotrexate alone. The study results were published in the journal The Lancet.  

Tubal ectopic pregnancies are a significant contributor to maternal morbidity and mortality. Methotrexate or surgery are the present management techniques.  Rescue surgery is planned in approximately 30% of women where methotrexate treatment fails. Gefitinib is an epidermal growth factor receptor inhibitor that improves the effects of methotrexate and disrupts the ectopic implantation site. Hence, researchers assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy.  

A multicenter, randomized, double-blind, placebo-controlled trial was carried out across 50 UK hospitals between Nov 2, 2016, and Oct 6, 2021. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m2) and randomized (1:1 ratio) to 7 days of additional oral gefitinib (250 mg daily) or placebo. The primary outcome was a surgical intervention to resolve the ectopic pregnancy as analyzed by intention to treat. Secondary outcomes included time to resolution of ectopic pregnancy and serious adverse events.  

Key findings: 

• Nearly 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). 
• Three participants in the placebo group withdrew. 
• The surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and 47 (29%) of 160 participants in the placebo group.
• The median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group Without surgical intervention. 
• Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and six (4%) of 162 participants in the placebo group.
• Diarrhea and rash were more common in the gefitinib group. 

Thus, adding oral gefitinib to standard medical treatment with methotrexate in women with a tubal ectopic pregnancy did not reduce the rate of surgical interventions. 

Further reading: Horne AW, Tong S, Moakes CA, et al. Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial [published online ahead of print, 2023 Feb 1]. Lancet. 2023;S0140-6736(22)02478-3. doi: 10.1016/S0140-6736(22)02478-3