Metronomic cyclophosphamide and bevacizumab for the treatment of recurrent gynecologic carcinosarcoma: A multi-institution, retrospective study.

Abstract

5532 Background: The recent findings from the GOG 261 trial established carboplatin and paclitaxel as the standard first-line therapy for advanced gynecologic carcinosarcoma (GCS). Response rates to alternative regimens are limited, and the optimal chemotherapy for later line treatment of gynecologic carcinosarcoma has not yet been determined. The objective of this retrospective study is to report clinical response to treatment regimens for patients with GCS treated at 2 large academic referral comprehensive cancer centers. Methods: This multi-institution, retrospective analysis identified patients with recurrent GCS treated between January 1, 2015 and August 1, 2020 at the Massachusetts General Hospital and the University of Alabama O’Neal Comprehensive Cancer Center. All eligible patients received platinum/taxane as their first-line treatment regimen and were subsequently treated for recurrent disease. Subsequent treatment strategies were investigated. Objective responses were determined based on the clinical radiologist’s interpretation. Time on treatment (TOT) and treatment toxicity were identified for each subject. Given the small number of patients in this series, descriptive statistics were employed. Results: 29 patients met inclusion criteria. 15 patients had recurrent uterine carcinosarcoma, and 14 patients had recurrent ovarian carcinosarcoma. The most commonly used treatment regimens were: liposomal doxorubicin (PLD)/bevacizumab (ORR: 13%; Range TOT: 2-7 months), metronomic oral cyclophosphamide (MOC)/bevacizumab (ORR: 17%; Range TOT: 1-18 months), weekly paclitaxel/bevacizumab (ORR 60%; Range TOT: 3-18.5 months), liposomal doxorubicin (PLD) (ORR: 0%; Range TOT: 1-3 months), and weekly paclitaxel (ORR: 33%; Range TOT: 4.5-5.5). All regimens were generally well tolerated, and only 3 patients discontinued treatment due to toxicity concerns. Conclusions: In summary, in our cohort of gynecologic carcinosarcoma patients, the most active regimen (defined by mean TOT) was paclitaxel/bevacizumab, but prolonged TOT was also observed in the patients treated with MOC/bevacizumab. Given the rarity and aggressive nature of this tumor, further studies into optimal second line chemo (and beyond) are warranted; although, the combination of MOC/bevacizumab should be considered given the tolerability and the duration of treatment in this patient population.