The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: A Gynecologic Oncology Group study

ObjectivesTo explore associations between histology and outcome in advanced or recurrent endometrial cancer patients participating in Gynecologic Oncology Group chemotherapy trials.MethodsAge, race, performance status, histologic type (serous = S; clear cell = CC; endometrioid = E), disease stage, and prior radiation were evaluated using various analytic methods to evaluate the probability of response and identify independent predictors of progression-free survival (PFS) and overall survival (OS).ResultsSingle agent or combination chemotherapy regimens including doxorubicin (A) (12%), doxorubicin/cisplatin (AP) (63%), doxorubicin/paclitaxel (AT) (13%), and paclitaxel/doxorubicin/cisplatin (TAP) (11%) were used among 1203 patients treated on 4 randomized clinical trials. Breakdown of disease stage was 7.8% stage III, 22.8% stage IV, and 69.4% recurrent disease. Histologic distribution was 18% S, 3.7% CC, 8.5% mixed, 51.7% E and 18.1% other. More S/CC patients enrolled on trials with advanced stage (III–IV) disease (as opposed to recurrent disease) compared to E patients (45% vs. 24%, p < 0.05). Overall response rate was 42% (E = 44%, S = 44%, CC = 32%). Histologic type was not an independent predictor of response. Independent predictors of PFS included race, performance status, disease stage, and CC histology. Histology was also an independent predictor of OS; the relative hazard ratio for S histology was 1.2 (1.02–1.4; p = 0.03), and for CC was 1.51 (1.1–2.07; p = 0.01).ConclusionIn patients with advanced/recurrent endometrial cancer treated with A, P and/or T, response was not associated with histology. This exploratory analysis does not support exclusion of S tumors in future trials. Poorer PFS and OS were observed in CC compared to other types, but a lack of benefit from chemotherapy was not shown, and as this histology represents such a small fraction, it does not seem feasible to have separate chemotherapy trials for CC.