PD-L1 expression and prognosis significance in advanced ovarian cancer

Abstract

Background: Recent data suggest that programmed death ligand 1 (PD-L1) expression may predict response to anti-programmed death 1 (PD-1) therapy. This retrospective observational study evaluated the prognostic effect of PD-L1+expression in patients with histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube cancer (OCa). Methods: Patients diagnosed with FIGO stages II-IV OCa from 2004-2012, at Aarhus University Hospital and Rigshospitalet, Copenhagen, Denmark, were included. PD-L1 expression was measured in tissue collected at OCa surgery, using immunohistochemistry with anti-PD-L1 22C3 antibody. PD-L1+ expression was defined as staining in>=1% of tumor or inflammatory cells. Patients partially sensitive (PPS; treatmentfree interval [TFI] of 6-12 mo) or fully sensitive (FPS; TFI>12 mo) to platinum therapy were considered platinum sensitive, whereas those refractory (TFI <3 mo) or resistant (TFI of 3-6 mo) to platinum were platinum insensitive. Data were analyzed using Cox proportional hazard model, adjusting for age, stage, histology, residual tumor, surgery type, performance status, and/or TFI. Results: Median age of the 376 patients at diagnosis was 63 years (range, 26-86). 77% had histologic grade 2/3 serous adenocarcinoma, 46% had residual tumor after surgery, and 9%, 70%, and 21% had FIGO stages II, III, and IV disease, respectively. FPS, PPS, platinum-resistant, and platinum-refractory disease comprised 49%, 27%, 15%, and 9% of patients, respectively. 50.5% of patients were PD-L1+, with prevalence increasing with increased platinum sensitivity (P for linear trend <0.05). Median overall survival (OS) was 43 mo (50.4 mo in PD-L1+ vs 38.3 mo in PD-L1- patients). A statistically significant association was seen between PD-L1+ tumors and longer OS (adjusted hazard ratio [aHR], 0.71 [95% CI, 0.55-0.91]). The association was not significant in platinum-insensitive patients (aHR, 0.82 [0.50-1.36]), but there was a tendency towards significance in platinum-sensitive patients (0.77 [0.57-1.06]), driven by those with a TFI of 6-12mo. Conclusions: PD-L1 was frequently expressed in advanced OCa patients, and expression may be prognostic, particularly in those with partially platinum-sensitive OCa.