Antonio Braga, MD
In a retrospective cohort study reported in The Lancet Oncology, Braga et al identified metastatic disease, choriocarcinoma histology, and higher pretreatment human chorionic gonadotropin concentration as independent predictors of resistance to single-agent chemotherapy in women with low-risk gestational trophoblastic neoplasia with International Federation of Gynecology and Obstetrics (FIGO) risk scores of 5 or 6. The findings may help spare patients from upfront multiagent therapy and its associated toxicity.
The study involved data from 431 eligible patients with a FIGO score of 5 or 6 (identified from among 5,020 with low-risk gestational trophoblastic neoplasia) treated at three reference centers in the United Kingdom, Brazil, and the United States between January 1964 and December 2018. Patients were excluded from analysis if they had received a nonstandard single-agent treatment or a previously established first-line multiagent chemotherapy regimen. The primary outcome measure was the incidence of chemoresistance after first-line or second-line single-agent chemotherapy.
Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors.— Braga et al
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All patients were followed for a minimum of 2 years.
Among the 431 eligible patients with a FIGO risk score of 5 or 6, 351 (81%) received a first-line single-agent treatment (74% treated from the year 2000 onwards). Among these, 103 (29%) developed resistance and were given a second single-agent regimen. Overall, 210 patients (60%) achieved remission with one or two sequential single-agent therapies; 141 patients (40%) developed resistance to single-agent treatments and required multiagent chemotherapy to achieve remission.
Compared with patients who achieved remission on single-agent treatment, those with chemoresistance had higher pretreatment human chorionic gonadotropin concentrations (P < .0001), a higher prevalence of choriocarcinoma histology (P = .0007), and a higher prevalence of metastatic choriocarcinoma (P = .0022).
On multivariate analysis, metastatic disease (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.1–3.2, P = .018), choriocarcinoma histology (OR = 3.7, 95% CI = 1.9–7.4, P = .0002), and pretreatment human chorionic gonadotropin concentration > 100,000 IU/L (OR = 2.8, 95% CI = 1.9–4.1, P < .0001) were significant independent predictors of resistance to single-agent therapies.
In patients without metastatic disease or choriocarcinoma, pretreatment human chorionic gonadotropin concentration of ≥ 411,000 IU/L was associated with a positive predictive value for resistance to single-agent therapy of 0.8. A positive predictive value of 0.8 was also found for a pretreatment human chorionic gonadotropin concentration of ≥ 149, 000 IU/L in patients with either metastatic disease or choriocarcinoma.
The investigators concluded, “Approximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors.”
Michael J. Seckl, FMedSci, of the Trophoblastic Tumour Screening and Treatment Centre, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, is the corresponding author for The Lancet Oncology article.
Disclosure: The investigators reported that there was no external funding for the study. For full disclosures of the study authors, visit thelancet.com.