Josee-Lyne Ethier1, Danielle N Desautels2, Eitan Amir3, Helen MacKay2. 1. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada. Electronic address: josee-lyne.ethier@uhn.ca. 2. Division of Medical Oncology and Hematology, Sunnybrook Health Sciences Centre, Toronto, Canada. 3. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada.
Abstract
BACKGROUND: Hormonal therapy (HT) is used commonly in the treatment of advanced endometrial cancer (EC). However, a 2010 Cochrane Review did not show a survival benefit for HT. Here, we quantify its effects and explore the influence of clinico-pathologic factors and hormone receptor (HR) status on overall response rates (ORR). METHODS: A systematic search of electronic databases identified publications of HT in advanced EC. Data from individual studies reporting ORR, median progression-free (PFS) or overall survival (OS) were weighted by individual study sample size and pooled in a meta-analysis. Outcomes of estrogen (ER) and progesterone receptor (PgR) subgroups were collected. Studies of first- and second-line HT were analyzed independently. Mixed studies were included if subgroup data based on previous HT exposure were provided. Meta-regression was performed to evaluate the influence of clinico-pathologic factors on outcomes. RESULTS: Thirty-nine studies were included, with seven providing subgroup data based on HR status. First-line HT was associated with a mean ORR of 21.6% and clinical benefit rate (CBR) of 36.7%. Median PFS and OS were 2.8 and 10.2months respectively. ORR was 20.4% in clinical trials and 25.3% in observational studies. Magnitude of ORR was lower in older age, adenosquamous histology and high grade. ORR was higher in ER+ (26.5%) and PgR+ (35.5%) disease, and lower in ER- (9.2%) or PgR- (12.1%) tumors. Second-line ORR was 18.5%. CBR was 35.8%, but was significantly associated with timing of stable disease assessments in first- and second-line. Meta-regression performed in mixed and second-line studies showed an association between previous HT and greater ORR (β 0.561; p=0.024), suggesting potential confounding by indication (re-treatment of good responders to first-line HT). CONCLUSION: HT is associated with modest ORR in advanced EC, and is greatest in HR+ tumors. Response rates in second-line are likely dependent on response to previous HT.
BACKGROUND: Hormonal therapy (HT) is used commonly in the treatment of advanced endometrial cancer (EC). However, a 2010 Cochrane Review did not show a survival benefit for HT. Here, we quantify its effects and explore the influence of clinico-pathologic factors and hormone receptor (HR) status on overall response rates (ORR). METHODS: A systematic search of electronic databases identified publications of HT in advanced EC. Data from individual studies reporting ORR, median progression-free (PFS) or overall survival (OS) were weighted by individual study sample size and pooled in a meta-analysis. Outcomes of estrogen (ER) and progesterone receptor (PgR) subgroups were collected. Studies of first- and second-line HT were analyzed independently. Mixed studies were included if subgroup data based on previous HT exposure were provided. Meta-regression was performed to evaluate the influence of clinico-pathologic factors on outcomes. RESULTS: Thirty-nine studies were included, with seven providing subgroup data based on HR status. First-line HT was associated with a mean ORR of 21.6% and clinical benefit rate (CBR) of 36.7%. Median PFS and OS were 2.8 and 10.2months respectively. ORR was 20.4% in clinical trials and 25.3% in observational studies. Magnitude of ORR was lower in older age, adenosquamous histology and high grade. ORR was higher in ER+ (26.5%) and PgR+ (35.5%) disease, and lower in ER- (9.2%) or PgR- (12.1%) tumors. Second-line ORR was 18.5%. CBR was 35.8%, but was significantly associated with timing of stable disease assessments in first- and second-line. Meta-regression performed in mixed and second-line studies showed an association between previous HT and greater ORR (β 0.561; p=0.024), suggesting potential confounding by indication (re-treatment of good responders to first-line HT). CONCLUSION: HT is associated with modest ORR in advanced EC, and is greatest in HR+ tumors. Response rates in second-line are likely dependent on response to previous HT.
Authors: Nicole Concin; Carien L Creutzberg; Ignace Vergote; David Cibula; Mansoor Raza Mirza; Simone Marnitz; Jonathan A Ledermann; Tjalling Bosse; Cyrus Chargari; Anna Fagotti; Christina Fotopoulou; Antonio González-Martín; Sigurd F Lax; Domenica Lorusso; Christian Marth; Philippe Morice; Remi A Nout; Dearbhaile E O'Donnell; Denis Querleu; Maria Rosaria Raspollini; Jalid Sehouli; Alina E Sturdza; Alexandra Taylor; Anneke M Westermann; Pauline Wimberger; Nicoletta Colombo; François Planchamp; Xavier Matias-Guiu Journal: Virchows Arch Date: 2021-02 Impact factor: 4.064
Authors: Anthony N Karnezis; Samuel Leung; Jamie Magrill; Melissa K McConechy; Winnie Yang; Christine Chow; Martin Kobel; Cheng-Han Lee; David G Huntsman; Aline Talhouk; Friederich Kommoss; C Blake Gilks; Jessica N McAlpine Journal: J Pathol Clin Res Date: 2017-10-14