The efficacy and safety of first-line single-agent chemotherapy regimens in low-risk gestational trophoblastic neoplasia: A network meta-analysis.

OBJECTIVE: There is no consensus regarding what should be the optimal single-agent regimen in low-risk gestational trophoblastic neoplasia(LRGTN). we performed this network meta-analysis(NMA) and our aim is to synthesize all efficacy evidence, enabling a comparison of all single-agent methotrexate(MTX)-based or actinomycin-d(Act-D)-based regimens in LRGTN.

METHODS: We performed a literature search of PubMed, Embase, and the Cochrane Library for all relevant articles. Seven randomized controlled trials and four retrospective studies met the study eligibility criteria. Overall, 987 patients were included. Treatments were grouped into weekly intramuscular MTX(w-IM MTX), five-day intramuscular MTX(5d-IM MTX), five-day intravenous MTX(5d-IV MTX), eight-day intramuscular MTX with folinic acid(MTX-FA), five-day intravenous Act-D(5d-IV Act-D), and bi-weekly pulsed intravenous Act-D (pulsed IV Act-D) treatments. P-score was used to rank the treatments.

RESULTS: Values of P-score indicated that the Act-D-based regimens had superior efficacy compared with the MTX-based regimens. Namely, 5d-IV Act-D had the highest probability of being the best treatment arm for CR, followed by pulsed IV Act-D and 5d-IV MTX. Similar results were observed in the subgroup analysis from the prospective studies. Toxicity analysis indicated that 5d-IM MTX showed increased toxicity in nausea and vomiting, as measured by their P-scores. In contrast, 5d-IV Act-D had the highest probability of being the least toxic regimen in terms of nausea and vomiting. Grade 3/4 adverse events (AEs), though infrequent, were more frequently observed in 5d-IM MTX, followed by 5d-IV Act-D and 5d-IV MTX.

CONCLUSIONS: Our NMA provides a systematic evaluation of the relative efficacy of available single-agent MTX-based and Act-D-based regimes in LRGTN. Until new evidence becomes available, 5d-IV Act-D and pulsed IV Act-D appear to be the best treatment options in LRGTN.