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Randomized Controlled Trial
. 2024 Jul 10;42(20):2425-2435.
doi: 10.1200/JCO.23.01279. Epub 2024 Apr 25.

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial

Ann H Klopp  1 , Danielle Enserro  2 , Matthew Powell  3 , Marcus Randall  4 , Julian C Schink  5 , Robert S Mannel  6 , Laura Holman  6 , David Bender  7 , Christina L Kushnir  8 , Floor Backes  9 , Susan L Zweizig  10 , Steven Waggoner  11 , Kristin A Bradley  12 , Lana DeSouza Lawrence  13 , Parviz Hanjani  14 , Christopher J Darus  15   16 , William Small Jr  17 , Higinia R Cardenes  18 , Jonathan M Feddock  19 , David S Miller  20
Affiliations
Randomized Controlled Trial

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial

Ann H Klopp et al. J Clin Oncol. .

Abstract

Purpose: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy.

Materials and methods: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS.

Results: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression.

Conclusion: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

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Conflict of interest statement

The following authors have no conflicts of interest to disclose: Dr. Ann Klopp, Dr. Susan Zweizig, Dr. Steven Waggoner, Dr. Lana de Souza Lawrence, Dr. Parviz Hanjani, Dr. Higinia Cardenes, Dr. William Small and Dr. Jonathan Feddock.

Dr. Danielle Enserro wishes to disclose that NCI support was received as Cooperative Grant/NCTN Grant funding for all aspects of this trial including travel to group meetings, statistical analysis, study monitoring, etc.

Dr. Matthew Powell acknowledges receiving consulting fees from the following: GlaxoSmithKline GSK/Tesaro, Merck, AstraZeneca, Clovis Oncology, Seagen and Eisai.

Dr. Marcus Randall reports receiving support for attending GOG/NRG travel and meeting support as Co-Chair of the Uterine Corpus Committee.

Dr. Robert Mannel and Dr. Laura Holman report institutional support received from NCI clinical trials network in support of this manuscript.

Dr. David Bender has received grants from Tesaro, Inc., AbbVie, Inc., AstraZeneca, Merck Sharp & Dohme Company, Clovis Oncology, Inc. and Genentech.

Dr. Christina Kushnir received consulting fees from Intuitive Surgical and Ethicon Biosurgery.

Dr. Floor Backes acknowledges research grants to Institution from Merck, Eisai, Immunogen, Clovis, BeiGene, Natera and Tempus. Dr. Backes received personal fees from UptoDate. Additionally, Dr. Backes received consulting fees from Agenus, Merck, Clovis, Immunogen, Eisai, AstraZeneca, GlaxoSmithKline, Myriad and Genentech. Dr. Backes also received personal fees for CME lectures from Clinical Educational Concepts, Clinical Care Options, Medscape/WebMD, Med Learning, 13Health, CMR Institute, Global Learning Initiative/Prova, OncLive. Dr. Backes served as a Board Member for the Society of Gynecologic Oncology (unpaid), Co-Chair for both NRG Oncology Developmental Therapeutics Committee and IGCS Education360.

Dr. Kristin Bradley reports serving as Treasurer of the American Brachytherapy Society (unpaid position) and is on the Board of Directors for the same.

Dr. Christopher Darus reports serving on the AstraZeneca Advisory Board and has received payments for the same. He also reports owning stock in Regeneron and Humanigen.

Dr. David Miller reports serving as Chair, Uterine Corpus Committee for GOG then NRG Oncology, 2003-2018.

Figures

Figure 1.
Figure 1.. CONSORT diagram.
CONSORT diagram depicting the flow of participants through the study. The study design and report are in accordance with the Consolidate Standard of Reporting Trials (CONSORT) statement.
Figure 2.
Figure 2.. Progression free and overall survival. Kaplan-Meier curve comparing progression-free survival (PFS) and overall survival (OS) for patients treated with chemoradiation (CRT) versus radiation alone (RT).
The x-axis represents time in months, and the y-axis represents the probability of remaining progression-free or alive overall. The solid line represents the PFS for the RT group, and the dashed line represents the PFS for the CRT group.
Figure 2.
Figure 2.. Progression free and overall survival. Kaplan-Meier curve comparing progression-free survival (PFS) and overall survival (OS) for patients treated with chemoradiation (CRT) versus radiation alone (RT).
The x-axis represents time in months, and the y-axis represents the probability of remaining progression-free or alive overall. The solid line represents the PFS for the RT group, and the dashed line represents the PFS for the CRT group.
Figure 3.
Figure 3.. Forest plot showing the analysis for potential prognostic (3A) and predictive factors per treatment arm (3B) for progression-free survival (PFS).
The x-axis represents the odds ratio (OR) for each predictive factor. The y-axis lists the predictive factors, and the horizontal lines extending from the squares represent the 95% CIs. Separate adjusted Cox proportional hazards models (stratified by performance status and tumor location, adjusted for treatment arm) were used to assess for prognostic associations between baseline factors and PFS. Separate adjusted Cox proportional hazards (stratified by performance status and tumor location, and including main effects of treatment and baseline factor plus an interaction term for treatment and baseline factor) were used to assess for predictive associations between PFS and baseline factors with treatment allocation.
Figure 3.
Figure 3.. Forest plot showing the analysis for potential prognostic (3A) and predictive factors per treatment arm (3B) for progression-free survival (PFS).
The x-axis represents the odds ratio (OR) for each predictive factor. The y-axis lists the predictive factors, and the horizontal lines extending from the squares represent the 95% CIs. Separate adjusted Cox proportional hazards models (stratified by performance status and tumor location, adjusted for treatment arm) were used to assess for prognostic associations between baseline factors and PFS. Separate adjusted Cox proportional hazards (stratified by performance status and tumor location, and including main effects of treatment and baseline factor plus an interaction term for treatment and baseline factor) were used to assess for predictive associations between PFS and baseline factors with treatment allocation.
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