Résumé
Background: Amongst metastatic breast cancer (MBC) patients (pts), those with triple-negative breast cancer (mTNBC) have a poor prognosis. Although chemotherapy (CT) remains the cornerstone therapy, its benefit on outcome is not established beyond second line while side effects increase and impair quality of life. Factors predicting for efficacy might help guiding in the treatment decision process. The purpose of this study was to evaluate factors predicting for progression-free survival (PFS) and overall survival (OS) in the third or fourth line treatment in pts with mTNBC within the National multicenter ESME cohort, and to build a nomogram based on the selected variables.
Methods: The ESME (Epidemiological Strategy and Medical Economics) MBC database (NCT03275311) is a unique national Metastatic Breast Cancer cohort built from existing information systems, pharmacy records and patients’ electronic medical records (EMR), with homogenous on-site collected information. This prospective cohort includes all consecutive pts who initiated a first-line treatment for a MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. We searched for independent prognostic factors under third and fourth line chemotherapy (PFS3 and PFS4, OS3 and OS4) for mTNBC patients, using COX proportional hazard regression models. Variables included in the model were pts and tumour (primary cancer and MBC) characteristics, as well as observed PFS under previous lines of therapy. We built prognostic nomograms based on main prognostic factors retrieved. Nomograms’ prediction ability were evaluated by concordance index (C-index), calibration and subgroup analysis. We used a 6-month cut-off for each PFSx.
Results: Among 22266 women in the ESME cohort, 2922 had a mTNBC. 1792 (61%), 1074 (37%) and 598 (20%) mTNBC pts respectively received at least 2, 3 or 4 lines of CT in the metastatic setting, with a median follow-up of 53.3 months (range 4.6-103). The median PFS3, PFS4, OS3 and OS4 were 2.3 months 95%CI [2.3-2.5], 2.1 months 95%CI [1.9-2.3], 6.6 months 95%CI [6.3-7.2] and 5.9 months 95%CI[5.2-6.4], respectively. PFS1, PFS2 and number of metastatic sites ≤3 at baseline were identified as prognostic factors by multivariate analysis both for OS3 and OS4 (HR 0.76 95%CI[0.66-0.88], HR 0.55 95%CI[0.46-0.65], HR 1.36 95%CI[1.14-1.62], all p<0.001, and HR 0.76 95%CI[0.63-0.91], p<0.001, HR 0.56 95%CI[0.45-0.7], p<0.001, HR 1.37 95%CI[1.07-1.74], p=0.01, respectively). In addition, disease free-interval between primary cancer and metastatic relapse was identified as an independent factor for OS3 (p=0.01) and PFS3 for OS4 (HR 0.75 95%CI[0.57-0.98], p=0.03). Median PFS3, PFS4, OS3 and OS4 according to previous duration of PFS are shown in Table 1. Nomograms predicting for PFS3, PFS4, OS3 and OS4 respectively achieved a C-index of 0.59, 0.58, 0.62, 0.61.
Conclusion: The previous duration of each PFS is a major prognostic factor of PFS and OS in TNBC in 3rd or 4rd of CT among mTNBC pts. However, nomograms predicting for PFS and OS this setting do not reach a clinical utilityTable 1: PFS and OS according to previous PFS duration
Previous PFS 1/2 (months)N=OS3 months [95%CI]HR [95%CI]pPFS3 months[95%CI]HR [95%CI]p≤6/≤65245.2 [4.7-5.9]1<0.0012.1 [1.9-2.2]1<0.001>6/≤63127.3 [6.4-8.7]0.71 [0.61; 0.82]2.4 [2.2-2.6]0.86 [0.75; 1]≤6/>611211.3 [8.1-13.4]0.48 [0.38; 0.6]2.7 [2.3-3.5]0.69 [0.56; 0.85]>6/>612611.9 [9.9-15.2]0.43 [0.34; 0.54]3.5 [3.2-4.1]0.52 [0.42; 0.64]Previous PFS1/2/3N=OS4 months [95%CI]HR [95%CI]PFS4 months [95%CI]HRp≤6/≤6 /≤62284.5 [3.9-5.4]1<0.0011.8 [1.6-1.9]1<0.001≤6/≤6 />6357.0 [4.1-10.9]0.7 [0.47; 1.04]2.1 [1.8-2.8]0.83 [0.57; 1.2]>6/≤6 />6176.9 [4.3-NA]0.7 [0.4; 1.22]3.0 [1.6-NA]0.54 [0.31; 0.94]>6/≤6 /≤61665.6 [4.7-6.7]0.65 [0.52; 0.8]2.3 [1.9-2.7]0.66 [0.54; 0.81]>6/>6 /≤6567.8 [4.9-11.1]0.54 [0.38; 0.75]2.1 [1.8-2.4]0.87 [0.64; 1.18]≤6/>6 /≤6608.1 [6.7-12.7]0.45 [0.33; 0.63]2.4 [1.9-3.0]0.65 [0.49; 0.88]≤6/>6 />61316.7 [5.9-NA]0.3 [0.16; 0.57]4.2 [2.3-NA]0.32 [0.17; 0.59]>6/>6 />62310.7 [8.5-NA]0.25 [0.14; 0.45]4.8 [3.4-8.0]0.33 [0.21; 0.51]
Citation Format: Luc Cabel, Matthieu Carton, Barbare Pistilli, Florence Dalenc, Laurence Vanlemnens, Christelle Levy, William Jacot, Marc Debled, Agnes Loeb, Bruno Coudert, Thubault De la Motte Rouge, Lilian Laborde, Carine Laurent, Emmanuel Chamorey, Damien Parent, Thierry Petit, Marie-Ange Mouret-Reynier, Geneviève Perrocheau, Claire Labreveux, Thomas Bachelot, Mathieu Robain, Florence Lerebours. Prediction of PFS and OS under third and fourth line chemotherapy among metastatic triple-negative breast cancer patients in the national multicenter ESME metastatic breast cancer cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-18.