Entrectinib use in a platinum-refractory mucinous ovarian cancer harboring a NTRK3 gene fusion.

Ovarian cancer is difficult to treat, and the mucinous epithelial subtype has a particularly poor response to traditional chemotherapy regimens. Entrectinib is a tumor-agnostic tyrosine kinase inhibitor with limited data regarding its use in ovarian cancers, though it demonstrates significant tumor response and patient tolerability in other settings. Here we outline what we believe to be the first case in which Entrectinib was successfully utilized to treat a patient with mucinous ovarian cancer. A 51-year-old woman with stage IVB mucinous ovarian cancer possessing a KANK1-NTRK3 gene fusion experienced tumor progression and clinical deterioration with conventional chemotherapeutics. Upon initiation of Entrectinib treatment she experienced rapid clinical improvement, with significant partial response and sustained decrease in tumor markers.

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab.

OBJECTIVE: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer. METHODS: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety. RESULTS: Among the 105 evaluable patients, the PFS rate at 18 months was 62% (95% CI 52-71%) in the overall population and 76% (95% CI 61-87) in the homologous recombination deficient (HRd), 47% (95% CI 31-64%) in the HR proficient (HRp), and 56% (95% CI 31-79%) in the HR not determined (HRnd) subgroups (December 24, 2020, cutoff). After a median follow-up time of 28.7 months (IQR, 23.9-32.5 months), median PFS was 19.6 months (95% CI 16.5-25.1) in the overall population (N = 105) and 28.3 months (95% CI 19.9-NE), 14.2 months (95% CI 8.6-16.8), and 12.1 months (95% CI 8.0-NE) in the HRd, HRp, and HRnd subgroups, respectively (June 16, 2021, cutoff). The most common any-grade treatment-related adverse events (related to niraparib and/or bevacizumab) were thrombocytopenia (74/105), fatigue (60/105), and anemia (55/105; December 24, 2020, cutoff). CONCLUSION: Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety profiles of niraparib and bevacizumab as monotherapy.

The end of life costs for Medicare patients with advanced ovarian cancer.

OBJECTIVE: To describe the Medicare payments at the end of life for patients with advanced ovarian cancer, and assess factors responsible for payment variation METHODS: Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified a cohort of women with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. We defined the end of life as the last 90days prior to death. Total medical costs were estimated from overall Medicare payments, and adjusted for geography and for inflation to the 2009 U.S. dollar. A generalized linear regression was performed to assess factors associated with variability in cost. RESULTS: Of 5509 patients, 78.9% died from ovarian cancer. In the 90days prior to death, 65.2% of patients had an inpatient admission, 53.7% received chemotherapy, 19.3% had a palliative procedure, and 62.5% had hospice services. The mean total payment per patient in the last 90days of life was $24,073 (range 0-$484,119) over the study time period. The mean cost of inpatient admissions was $14,529 (range 0-$483,932). On a multivariate analysis, costs at the end of life did not vary based on length of patient survival (p=0.77). Factors associated with significantly increased costs in the last 90days of life were medical comorbidity, chemotherapy, time spent as an inpatient, and admissions associated with emergency room visits. CONCLUSIONS: Reducing the prescription of chemotherapy and increasing the use of hospice services for ovarian cancer patients at the end of life will aid in lowering costs.

The Cost of Initial Care for Medicare Patients With Advanced Ovarian Cancer.

OBJECTIVES: In preparation for payment reform, we evaluated Medicare payments for the initial treatment of patients with advanced ovarian cancer and assessed factors responsible for variation. METHODS: Using the linked SEER-Medicare database, we identified a cohort of 9,491 women aged 65 years or older with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. Diagnostic and procedural codes specific to the care of ovarian cancer were used to estimate total medical costs for the treatment of ovarian cancer. Costs were adjusted for geography and for inflation to the 2009 US dollar. NCCN Guideline-consistent care was defined as surgery and 6 cycles of chemotherapy. A generalized linear regression was performed to assess factors associated with variability in cost. RESULTS: The mean total payment per patient in the initial treatment period was $65,908 (range of means, $30,745-$96,360). Increasing medical comorbidity, use of PET/CT, surgical complications, and readmissions were associated with increased costs. Treatment with NCCN Guideline-consistent surgery and chemotherapy had a mean annual cost of $85,987 compared with $89,149 for non-NCCN Guideline-consistent treatment with surgery and chemotherapy. The cost of surgery and chemotherapy that was not consistent with NCCN Guidelines was approximately $7,000 more than the cost of therapy that was consistent (P<.001) CONCLUSIONS: The financial burden of caring for patients with ovarian cancer is substantial. Treatment that is consistent with NCCN recommendations for treating advanced ovarian cancer, which is shown to have improved outcomes, is not associated with higher cost.

Ovarian cancer outcomes: Predictors of early death.

OBJECTIVE: To describe the outcomes and mortality in advanced ovarian cancer patients in a population-based cohort in the 90 days after diagnosis. METHODS: Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified a cohort of women with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. A χ(2) test was used to assess demographic and clinical factors. Kaplan-Meier curves and Cox proportional hazards models were used to assess factors associated with variation in survival. RESULTS: Of the 9491 patients with stage III/IV ovarian cancer identified from the SEER/Medicare system, 4131 (43.6%) patients died in the first year after diagnosis. Of these, 2472 (26.0%) patients died in the first 90 days after diagnosis. Over the study period, the number of patients who died in the first 90 days after diagnosis slightly increased (p=0.053). Older age (>75 years of age), increased comorbidity, stage IV disease, lack of a visit with a gynecologic oncologist, and surgery were associated with an increase in 90-day mortality. Chemotherapy was associated with a reduction in 90-day mortality. CONCLUSIONS: Approximately 25% of patients with advanced ovarian cancer in our study period died within 90 days of diagnosis, and more than 40% died within the first year of diagnosis. In addition, a substantial proportion of patients did not receive any treatment. Further research into the characteristics of these patients should be performed to elucidate clinical areas for intervention to either prevent these poor outcomes or allocate appropriate resources to patients with extremely poor prognoses.