Circulating Tumor Cells Count-Based Nomograms To Predict Survival Of Metastatic Breast Cancer Patients: Results From The European Pooled Analysis

Background: The European Pooled Analysis of CTC (EPAC) in metastatic breast cancer, based on 1,944 individual data from patients with various tumor types and clinical settings (Bidard et al, Lancet Oncol 2014), has established CTC count (CellSearch) at baseline and during therapy as a level of evidence 1 independent prognostic biomarker and demonstrated its superiority over serum blood markers. As part of the study pre-planned objectives, we sought to establish nomograms allowing accurate individual survival predictions. Methods: Using individual data from 17 centers, we built simplified multivariate prognostic models taking into account the independent prognostic clinico-pathological (CP) characteristics including CTC count, dichotomized using the 5CTC/7.5ml threshold, at baseline and at 3-5 weeks after the start of a new treatment regimen, and derived nomograms for progression-free survival (PFS) and overall survival (OS) prediction at baseline and after 3-5 weeks of treatment. We report here the internal validation of these nomograms. Discrimination of the models was assessed using the c-index estimated by a jackknife procedure and the calibration was visually assessed through 10-fold crossvalidated calibration plots at 1,2,3 years for OS and 1,2 years for PFS. Results: Multivariate models at baseline for PFS and OS were fitted on 1501 and 568 individual patient data with CTC count at baseline and CTC count at baseline and after 3-5 weeks, respectively. Models include tumor subtype, the number of previous chemotherapy lines (0/1/≥2), PS, age ( 50-65/u003e65 years), metastasis-free intervals (0/u003e0-3/u003e3 years), metastatic sites (liver and CNS) and CTC count at baseline and eventually at 3-5 weeks of treatment. The C-index increased from 0.722 to 0.755 (increase in C-index:0.033, 95% CI [0.019;0.045]) when adding baseline CTC to the CP only model for OS (n=1501). For those patients with CTC values at 3-5 weeks (n=568), there was an additional increase in the C-index when adding CTC at 3-5 weeks to a model with already CP and baseline CTC from 0.731 to 0.743 (increase in C-index 0.013, 95% CI [-0.004;0.025]). The model with CP and baseline CTC counts showed a good calibration for OS at 1,2,3 years and the model with CP, baseline CTC and CTC count at 3-5 weeks a moderately good calibration. Similar results were obtained for PFS. Conclusion: From the largest database with individual CTC data, we were able to build PFS and OS survival nomograms, with satisfactory discrimination and calibration. Our planned next step is to validate the nomogram in an additional cohort. Citation Format: Bidard F-C, Peeters D, Fehm T, Nole F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, Fernandez de Lascoiti A, de Mattos-Arruda L, Ignatiadis M, van Laere SJ, Meier-Stiegen F, Sandri M-T, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson S-J, Raimondi C, Rutten A, Janni W, Munzone E, Caranana V, Agelaki S, Almici C, Dirix L, Solomayer E, Zorzino L, Reis-Filho JS, Squifflet P, Pantel K, Beije N, Sleijfers S, Pierga J-Y, Michiels S. Circulating tumor cells count-based nomograms to predict survival of metastatic breast cancer patients: Results from the European pooled analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-08.