Phase III trial: Adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/ carboplatin in high-intermediate and high-risk early stage endometrial cancer

Marcus E. Randall, Virginia Filiaci, D. Scott McMeekin, Vivian Von Gruenigen, Helen Huang, Catheryn M. Yashar, Robert S. Mannel, Jae Weon Kim, Ritu Salani, Paul A. DiSilvestro, James J. Burke, Thomas Rutherford, Nick M. Spirtos, Keith Terada, Penny R. Anderson, Wendy R. Brewster, William Small, Carol A. Aghajanian, David S Miller

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Abstract

PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

Original languageEnglish (US)
Pages (from-to)1810-1818
Number of pages9
JournalJournal of Clinical Oncology
Volume37
Issue number21
DOIs
StatePublished - Jul 20 2019

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Carboplatin
Brachytherapy
Endometrial Neoplasms
Paclitaxel
Radiotherapy
Drug Therapy
Recurrence
Survival
Histology
Gynecology
Obstetrics
Area Under Curve
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase III trial : Adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/ carboplatin in high-intermediate and high-risk early stage endometrial cancer. / Randall, Marcus E.; Filiaci, Virginia; McMeekin, D. Scott; Von Gruenigen, Vivian; Huang, Helen; Yashar, Catheryn M.; Mannel, Robert S.; Kim, Jae Weon; Salani, Ritu; DiSilvestro, Paul A.; Burke, James J.; Rutherford, Thomas; Spirtos, Nick M.; Terada, Keith; Anderson, Penny R.; Brewster, Wendy R.; Small, William; Aghajanian, Carol A.; Miller, David S.

In: Journal of Clinical Oncology, Vol. 37, No. 21, 20.07.2019, p. 1810-1818.

Research output: Contribution to journalArticle

Randall, ME, Filiaci, V, McMeekin, DS, Von Gruenigen, V, Huang, H, Yashar, CM, Mannel, RS, Kim, JW, Salani, R, DiSilvestro, PA, Burke, JJ, Rutherford, T, Spirtos, NM, Terada, K, Anderson, PR, Brewster, WR, Small, W, Aghajanian, CA & Miller, DS 2019, 'Phase III trial: Adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/ carboplatin in high-intermediate and high-risk early stage endometrial cancer', Journal of Clinical Oncology, vol. 37, no. 21, pp. 1810-1818. https://doi.org/10.1200/JCO.18.01575
Randall, Marcus E. ; Filiaci, Virginia ; McMeekin, D. Scott ; Von Gruenigen, Vivian ; Huang, Helen ; Yashar, Catheryn M. ; Mannel, Robert S. ; Kim, Jae Weon ; Salani, Ritu ; DiSilvestro, Paul A. ; Burke, James J. ; Rutherford, Thomas ; Spirtos, Nick M. ; Terada, Keith ; Anderson, Penny R. ; Brewster, Wendy R. ; Small, William ; Aghajanian, Carol A. ; Miller, David S. / Phase III trial : Adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/ carboplatin in high-intermediate and high-risk early stage endometrial cancer. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 21. pp. 1810-1818.
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title = "Phase III trial: Adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/ carboplatin in high-intermediate and high-risk early stage endometrial cancer",
abstract = "PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74{\%} had stage I disease. Histologies included endometrioid (71{\%}), serous (15{\%}), and clear cell (5{\%}). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95{\%} CI, 0.70 to 0.81) for RT and 0.76 (95{\%} CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90{\%} confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95{\%} CI, 0.83 to 0.91) for RT and 0.85 (95{\%} CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90{\%} confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9{\%} v 4{\%}). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.",
author = "Randall, {Marcus E.} and Virginia Filiaci and McMeekin, {D. Scott} and {Von Gruenigen}, Vivian and Helen Huang and Yashar, {Catheryn M.} and Mannel, {Robert S.} and Kim, {Jae Weon} and Ritu Salani and DiSilvestro, {Paul A.} and Burke, {James J.} and Thomas Rutherford and Spirtos, {Nick M.} and Keith Terada and Anderson, {Penny R.} and Brewster, {Wendy R.} and William Small and Aghajanian, {Carol A.} and Miller, {David S}",
year = "2019",
month = "7",
day = "20",
doi = "10.1200/JCO.18.01575",
language = "English (US)",
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TY - JOUR

T1 - Phase III trial

T2 - Adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/ carboplatin in high-intermediate and high-risk early stage endometrial cancer

AU - Randall, Marcus E.

AU - Filiaci, Virginia

AU - McMeekin, D. Scott

AU - Von Gruenigen, Vivian

AU - Huang, Helen

AU - Yashar, Catheryn M.

AU - Mannel, Robert S.

AU - Kim, Jae Weon

AU - Salani, Ritu

AU - DiSilvestro, Paul A.

AU - Burke, James J.

AU - Rutherford, Thomas

AU - Spirtos, Nick M.

AU - Terada, Keith

AU - Anderson, Penny R.

AU - Brewster, Wendy R.

AU - Small, William

AU - Aghajanian, Carol A.

AU - Miller, David S

PY - 2019/7/20

Y1 - 2019/7/20

N2 - PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

AB - PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

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