Novel Algorithm May Guide Chemotherapy For FIGO 5–6 Gestational Trophoblastic Neoplasia

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Human chorionic gonadotropin (hCG) concentration, histology and the presence of metastatic disease can help identify patients with FIGO risk score 5 or 6 gestational trophoblastic neoplasia who will benefit from multiagent chemotherapy, researchers report in The Lancet Oncology. 

Michael Seckl, from Charing Cross Hospital in London, UK, and co-workers explain that while patients with a FIGO risk score of 5 or 6 are considered to be at low risk of developing resistance to single-agent chemotherapy, only a third will achieve complete remission after their first treatment. 

“Consequently, some investigators recommend that all women with a FIGO risk score of 5 or 6 receive first-line multiagent therapy, which is considerably more toxic than single-agent therapy”, they explain. 

The team examined for predictive factors of single-agent resistance in a cohort of 431 patients, aged a median 31 years, with gestational trophoblastic neoplasia and a FIGO risk score of 5 or 6 who were treated between 1964 and 2018 in the UK, USA or Brazil. 

Overall, 60% of patients achieved remission after one or two uses of a single-agent therapy delivered sequentially, while 40% of patients developed resistance and required multiagent chemotherapy to achieve remission. 

Multivariable analyses revealed that patients with chemoresistance were significantly more likely to have a hCG concentration above 100,000 IU/L than those who did not, and were more likely to have choriocarcinoma histopathology and metastatic disease, with odds ratios of 2.8, 3.7 and 1.9, respectively. 

The researchers created a novel risk classification system, grouping patients as having no choriocarcinoma or metastases; choriocarcinoma only; metastatic disease only; or both choriocarcinoma and metastases. 

Finding that 72% of the 18 patients with metastatic choriocarcinoma did not achieve remission on single-agent therapy regardless of hCG level, the investigators recommend that these patients undergo first-line multiagent chemotherapy. 

For the 68 patients with one risk factor (choriocarcinoma or metastases), a median pretreatment hCG concentration of 149,000 IU/L identified 12 patients who were resistant to single-agent chemotherapy giving a positive predictive value of 1.0. 

And among the 182 patients without either risk factor, a hCG threshold of 411,000 IU/L gave a positive predictive value of 0.86, where six of the seven patients identified had resistance to single-agent chemotherapy. 

These risk factors and hCG thresholds were used to devise a novel algorithm for directing patients to first-line methotrexate or dactinomycin chemotherapy or first-line multiagent chemotherapy with cyclophosphamide and vincristine. 

“This risk-stratified approach might help maximise initial responses to therapy, while minimising unnecessary excessive exposure to toxic multiagent chemotherapy”, write Michael Seckl and co-authors. 

Nevertheless, they emphasize that “this rare group of patients should be referred to a gestational trophoblastic neoplasia reference centre whenever possible to obtain expert diagnosis and ensure proper treatment.” 

Writing in a linked comment, Gabriella Ferrandina, from UOC Ginecologia Oncologica, and Giovanni Scambia, from Istituto di Ginecologia e Ostetricia, both based in Rome, Italy, say the “study has provided potentially useful findings for implementation of personalised therapeutic approaches.” 

Nevertheless, they recommend that the FIGO staging system for gestational trophoblastic neoplasia be updated based on the risk of chemoresistance. 

And the commentators also highlight ongoing research into use of first-line paclitaxel plus carboplatin for metastatic disease, as well as studies assessing the use of avelumab alone or with methotrexate in different risk groups. 

References 

Braga A, Paiva G, Ghorani E, et al. Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study. Lancet Oncol; Advance online publication 25 June 2021. DOI: 10.1016/S1470-2045(21)00262-X  

Ferrandina G, Scambia G. Improving single-agent chemoresistance risk identification in gestational trophoblastic neoplasia. Lancet Oncol; Advance online publication 25 June 2021. DOI: 10.1016/S1470-2045(21)00327-2