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

Author(s): Ann H. Klopp, MD, PhD¹; Danielle Enserro, PhD²; Matthew Powell, MD³; Marcus Randall, MD⁴; Julian C. Schink, MD⁵; Robert S. Mannel, MD⁶; Laura Holman, MD⁶; David Bender, MD⁷; Christina L. Kushnir, MD, MPH⁸; Floor Backes, MD⁹; Susan L. Zweizig, MD¹⁰; Steven Waggoner, MD¹¹; Kristin A. Bradley, MD¹²; Lana DeSouza Lawrence, MD¹³; Parviz Hanjani, MD¹⁴; Christopher J. Darus, MD^15,16; William Small Jr, MD¹⁷; Higinia R. Cardenes, MD, PhD¹⁸; Jonathan M. Feddock, MD¹⁹; David S. Miller, MD²⁰

Source: https://doi.org/10.1200/JCO.23.01279

Dr. Anjan Patel's Thoughts

For patients with local recurrences of endometrial cancer, XRT alone is extremely effective, and the addition of cisplatin does not offer any benefit while increasing toxicity. These patients with low-grade and vaginal recurrences have a good prognosis and most should be treated with XRT alone.

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.

Author Affiliations

¹Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; ²Clinical Trials Development Division, Roswell Park Comprehensive Cancer Center, Buffalo, NY; ³Washington University School of Medicine, Obstetrics & Gynecology, St Louis, MO; ⁴University of Kentucky, Radiation Oncology, Lexington, KY; ⁵Cancer Treatment Centers of America, City of Hope, Gynecologic Oncology, Chicago, IL; ⁶University of Oklahoma Health Sciences, Oklahoma City, OK; ⁷University of Iowa Hospitals & Clinics, Iowa City, IA; ⁸Women’s Cancer Center of Nevada, Las Vegas, NV; ⁹The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, OH; ¹⁰University of Massachusetts Memorial Health Care, Gynecologic Oncology, Worcester, MA; ¹¹Cleveland Clinic Foundation, Medical Oncology, Cleveland, OH; ¹²University of Wisconsin Hospital and Clinics, Radiation Oncology, Madison, WI; ¹³Delaware/Christiana Care, Radiation Oncology, Newark, DE; ¹⁴Abington Memorial Hospital, Gynecologic Oncology, Abington, PA; ¹⁵Maine Medical Center, Gynecologic Oncology, Scarborough, ME; ¹⁶Providence Gynecologic Oncology Program and Earle A Chiles Research Institute, Portland, OR; ¹⁷Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Cardinal Bernardin Cancer Center, Chicago, IL; ¹⁸New York-Presbyterian Hospital, Weill Cornell Medicine, Clinical Radiation Oncology, New York, NY; ¹⁹Baptist Health, Radiation Oncology, Lexington, KY; ²⁰University of Texas Southwestern Medical Center, Gynecologic Oncology, Dallas, TX

Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors

Study showing feasibility and possible improvements in DFS with chemo + pembro vs. chemo alone in the adjuvant setting of resected endometrial cancer in dMMR patients. While a nice idea / proof of principle, I would be more interested in how IO alone performs vs. chemo in this setting, particularly if a brief course of neoadjuvant IO is given prior to surgery.

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

Initial results from the DUO-E study in metastatic endometrial cancer. The preliminary report suggests that maintenance durvalumab and maintenance durvalumab + olaparib were superior to standard observation after systemic carbo/taxol. As the trial data matures, the question will be: is this in all patients or driven by those with dMMR or HDR mutations?

Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer

This is another possibility for maintenance therapy. It will require further study.

Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer

An interesting study where the authors performed a post hoc analysis of randomized trials using molecular classification of endometrial cancers. There was good evidence to omit RT for those with POLE mutations and def-MMR. There seems to be a higher degree of benefit in those with a p53 mutation.

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer

Large phase III study of carbo/taxol+pembro x 6 followed by pembro alone x 14 cycles in metastatic endometrial cancer. There was a benefit in both pMMR and dMMR patients, although the magnitude was unsurprisingly higher in those with dMMR. OS results are still pending, and carcinosarcoma-type histology was excluded. This combination has been approved and is on NCCN as a cat-1 recommendation.