Introduction Gestational trophoblastic diseases and neoplasias (GTDs and GTNs) comprise a spectrum of diseases arising from abnormally proliferating placental/trophoblastic tissue following an antecedent molar or non-molar pregnancy. These can spread to the brain hematogenously in about 10% of patients, mostly in high-risk disease. The optimal management of patients with brain metastases from GTN is unclear, with multiple systemic regimens under use and an uncertain role for radiotherapy.Areas covered Here, we review the epidemiology, workup, and treatment of GTN with central nervous system (CNS) involvement. Literature searches in PubMed and Google Scholar were conducted using combinations of keywords such as 'gestational trophoblastic disease,' 'gestational trophoblastic neoplasia,' 'choriocarcinoma,' and 'brain metastases.'Expert opinion Systemic therapy is the frontline treatment for GTN with brain metastases, and radiotherapy should only be considered in the context of a clinical trial or for resistant/recurrent disease. Surgery has a limited role in palliating symptoms or relieving intracranial pressure/bleeding. Given the highly specialized care these patients require, treatment at a high-volume referral center with multidisciplinary collaboration likely leads to better outcomes. Randomized trials should be conducted to determine the best systemic therapy option for GTN.
To quantify early dissemination patterns, factors influencing use, and costs of bevacizumab (BEV) for the treatment of newly diagnosed ovarian cancer (OC) in the United States before its regulatory approval for this indication (off-label use).We identified women 18-65 years of age with newly diagnosed OC treated with surgery and platinum-based chemotherapy from 2008 to 2016 through the MarketScan database (N = 8,109). The proportion of women receiving BEV over time was calculated, multivariate logistic regression used to determine factors associated with BEV use, and total costs per cycle of chemotherapy with and without BEV abstracted.BEV utilization rose 1.8-fold during the study period, from 4.1% (2008) to 7.4 % (2016). BEV was used with non-platinum/taxane regimens over a third of the time (37.2%). Physician specialty (medical oncology v gyn oncology) and geography (southeast region) were significantly associated with higher rates of use. Clinical factors associated with BEV use were metastatic disease and presence of ascites. The median cost of one cycle of platinum/taxane chemotherapy plus BEV was $10,897 in US dollars (USD) (interquartile range $7,573-$18,133 USD), compared with $1,629 USD (interquartile range, $683.0-$4,461 USD) for platinum/taxane alone.Off-label use of BEV for newly diagnosed OC was rare (< 10%), but doubled following presentation of phase II and III data at international meetings. Both clinical (ascites, metastatic disease, and age) and nonclinical (specialty and region) factors were associated with BEV use, and its use was accompanied by a six-fold increase in the cost of one cycle of treatment.
e17050 Background: Activin receptor-like kinase 1 (ALK1) drives the maturation phase of angiogenesis. We conducted a two-stage, phase II trial of dalantercept, a soluble ALK1 inhibitor receptor fusion protein, in patients with persistent or recurrent ovarian, fallopian tube or primary peritoneal carcinoma, with correlative endpoints. Methods: Eligibility criteria included measurable disease, 1-2 prior cytotoxic regimens and GOG performance status (PS) ≤ 2. Dalantercept was administered subcutaneously at 1.2 mg/kg every 3 weeks until disease progression or development of unacceptable toxicity. The primary null hypothesis was response rate ≤ 0.10 and rate of ≥ 6-month progression-free survival without receipt of non-protocol therapy (EFS-6) ≤ 0.15, using RECIST 1.1 criteria. Tumor and plasma biomarkers were assessed by immunohistochemistry (IHC), gene expression, and ELISA in an exploratory fashion in association with EFS-6, with an unadjusted p-value of < 0.05 considered interesting. Results: The first stage was closed after enrollment of 30 participants with median age of 56.5 years, high-grade serous histology in 76.7%, 2 prior regimens in 46.7%, and platinum-free interval ≤ 6 months in 73.3%. All participants discontinued dalantercept, 24 (80.0%), 5 (16.7%) and 1 (3.3%) due to progression, toxicity, and other reason, respectively. The median number of treatment cycles per patient was 2 (range 1 – 29). There were six treatment-related grade 3 AEs and no grade ≥ 4 AEs. There were no objective responses. EFS-6 was 20% (6 out of 30 participants, 90% CI 9.1% to 35.7%). Biomarkers deemed interesting were BMP10 IHC score (worse EFS-6, HR 2.85); plasma BMP9 (improved EFS-6, HR 0.36); plasma VEGF (worse EFS-6, HR 3.45). ALK1 tumor IHC or plasma level was not associated with outcome. Four of 125 genes were deemed interesting. Conclusions: Though well tolerated, dalantercept as administered had limited efficacy in this patient population overall. Several biomarkers consistent with dalantercept’s proposed mechanism of action were associated with the primary outcome, but these associations will require further validation through properly controlled follow-up studies. Clinical trial information: NCT01720173.
In Brief OBJECTIVE: To identify factors associated with increased 30-day mortality after advanced ovarian cancer debulking among elderly women. METHODS: A database linking Medicare records with the Surveillance, Epidemiology, and End Results (SEER) data was used to identify a cohort of 5,475 women aged 65 and older who had primary debulking surgery for stage III or IV epithelial ovarian cancer (diagnosed 1995–2005). Women were stratified by acuity of hospital admission. Multivariable analysis was performed to identify patient-related and treatment-related variables associated with 30-day mortality. RESULTS: Five thousand four hundred seventy-five women had surgery for advanced ovarian cancer, and the overall 30-day mortality was 8.2%. Women admitted electively had a 30-day mortality of 5.6% (251 of 4,517), and those admitted emergently had a 30-day mortality of 20.1% (168 of 835). Advancing age, increasing stage, and increasing comorbidity score were all associated with an increase in 30-day mortality (all P<.05) among elective admissions. A group of women at high risk admitted electively included those aged 75 or older with stage IV disease and women aged 75 or older with stage III disease and a comorbidity score of 1 or more. This group had an observed 30-day mortality of 12.7% (95% confidence interval 10.7%–14.9%). CONCLUSION: Age, cancer stage, and comorbidity scores may be helpful to stratify electively admitted patients based on predicted postoperative mortality. If validated in a prospective cohort, then these factors may help identify women who may benefit from alternative treatment strategies. LEVEL OF EVIDENCE: II Thirty-day mortality after surgery for advanced ovarian cancer in an elderly population is 5.6% for elective admissions and more than 20% after emergency admissions.
Abstract Background A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma. Methods Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided Z test for 2 proportions. Adverse events (AEs) were evaluated per CTCAE version 4. Results One hundred and fifty-eight patients were randomized, out of which 9 were ineligible and 12 were not evaluable for the primary endpoint, leaving 137 eligible and evaluable. 6-month PFS was 46.6% in the cediranib arm versus 24.5% in the placebo arm (P = .005). There was no significant difference in overall survival between the 2 arms. There was more grade ≥ 3 AEs in the cediranib arm than in the placebo arm (P = .02). Conclusions This study met its primary endpoint of prolongation of 6-month PFS with cediranib in combination with radiation and temozolomide versus placebo in combination with radiation and temozolomide. There was no difference in overall survival between the 2 arms.
