Low probability of disease cure in advanced ovarian carcinomas before the PARP inhibitor era
Benoît You, Lilian van Wagensveld, Michel Tod, Gabe S. Sonke, Hugo M. Horlings, Roy F.P.M. Kruitwagen, Andreas du Bois, Frédèric Selle, Timothy Perren, Jacobus Pfisterer, Florence Joly, Adrian Cook, Marie Christine Kaminsky, K. Wollschlaeger, Alain Lortholary, Oliver Tomé, Alexandra Léary, Gilles Freyer, Maaike A. van der Aa, Olivier Colomban
Abstract
BACKGROUND: In ovarian carcinomas, the likelihood of disease cure following first-line medical-surgical treatment has been poorly addressed. The objective was to: (a) assess the likelihood of long-term disease-free (LDF) > 5 years; and (b) evaluate the impact of the tumour primary chemosensitivity (assessed with the modelled CA-125 KELIM) with respect to disease stage, and completeness of debulking surgery. METHODS: Three Phase III trial datasets (AGO-OVAR 9; AGO-OVAR 7; ICON-7) were retrospectively investigated in an "adjuvant dataset", whilst the Netherlands Cancer Registry was used in a "neoadjuvant dataset". The prognostic values of KELIM, disease stage and surgery outcomes regarding the likelihood of LDF were assessed using univariate/multivariate analyses. RESULTS: Of 2029 patients in the "adjuvant dataset", 82 (4.0%) experienced LDF (Stage I-II: 25.9%; III: 2.1%; IV: 0.5%). Multivariate analyses identified disease stage and KELIM (OR = 4.24) as independent prognostic factors. Among the 1452 patients from the "neoadjuvant dataset", 36 (2.4%) had LDF (Stage II-III: 3.3%; IV: 1.3%). Using multivariate tests, high-risk diseases (OR = 0.18) and KELIM (OR = 2.96) were significant. CONCLUSION: The probability of LDF > 5 years after first-line treatment in 3486 patients (<4%) was lower than thought. These data could represent a reference for future studies meant to assess progress related to PARP inhibitors.