Is Etoposide-Methotrexate-Actinomycin D a Preferred Chemotherapy Regimen for Most Patients With High-Risk Gestational Trophoblastic Neoplasms?

After accounting for confounding factors, results of a retrospective study of patients with gestational trophoblastic neoplasia (GTNs) treated with a first-line multiagent chemotherapy regimen showed similar clinical outcomes for those treated with etoposide, methotrexate, and actinomycin D (EMA) compared with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO).

GTNs represent a rare, diverse group of malignant neoplasms related to pregnancy that result from abnormal proliferation of trophoblastic tissue. These tumors are very sensitive to chemotherapy and considered to be highly curable even in the presence of metastatic disease. Furthermore, many women with a GTN remain fertile following treatment.

While single-agent chemotherapy is often considered appropriate for patients with low-risk GTNs, including those with FIGO stage I disease or FIGO stage II or III disease with a World Health Organization (WHO) prognostic score of 7 or lower, multiagent chemotherapy is typically recommended for patients with high-risk disease characterized by FIGO stage IV disease or FIGO stage II or III disease with a score of 7 or higher on the WHO prognostic scoring system.²

Regarding multiagent chemotherapy, EMACO is the most commonly used regimen, although EMA has been previously reported to have comparable effectiveness compared with EMACO with lower rates of anemia.

In this study, patient-, disease-, and treatment-related characteristics of 83 patients diagnosed with GTN at the New England Trophoblastic Disease Center and treated with EMA (44 individuals) or EMACO (39 individuals) during the period from 1986 to 2019 were accessed from their medical records.¹

Significant differences in the baseline characteristics of these 2 groups of patients included a higher percentage of patients with stage IV disease (P =.008), a higher median WHO prognostic score (P <.001), and a higher percentage of patients with tumor size of 3 cm or higher (P <.001) in the EMACO group compared with the EMA group.

Although the complete remission rate (CR) was significantly higher for patients receiving EMA (97.7%) compared with EMACO (71.8%; P =.001), this difference was no longer significant following multivariate analysis that controlled for prognostic factors.

Similarly, no differences were observed for patients receiving the 2 different chemotherapy regimens regarding median time to CR — 12 weeks for EMA group and 13.1 weeks for EMACO group — or in the percentages of patients experiencing a treatment delay or undergoing adjuvant surgery.

Regarding safety, patients treated with EMA experienced 55 episodes of grade 2 or higher neutropenia compared with only 16 episodes in those receiving EMACO, although the use of growth factor support was higher in the EMACO group (48.7%) compared with EMA group (18.2%; P =.003).

In their concluding remarks, the study authors noted that “it may be worthwhile to investigate whether EMA, a simpler and less costly regimen, may be as effective as EMACO in the treatment of GTN.”

References

1. Jareemit N, Horowitz NS, Goldstein DP, et al. EMA vs EMACO in the treatment of gestational trophoblastic neoplasia. Gynecol Oncol [published online May 11, 2020] . doi: 10.1016/j.ygyno.2020.04.699
2. Ngan HYS, Secki MJ, Berkowitz RS, et al. Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet. 2015;131 (Suppl 2):S123-126.