Abstract P1-01-02: Circulating tumor cells (CTC) and endothelial cells (CEC) prognostic value in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab: First results of a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET study
Authors: Pierga J-Y , Tredant O , Chevrier M , Dubot C , Lorgis V , Romieu G , Goncalves A , Debled M , Levy C , Ferrero J-M , Jouannaud C , Luporsi E , Mouret-Reynier M-A , Dalenc F , Berger F , Lemonnier J , Proudhon C , Bidard F-C 
Published: March 2017

Abstract
Background: increased levels of circulating tumor cells (CTC) are associated with worse progression-free survival (PFS) and overall survival (OS) in patients (pts) with metastatic breast cancer (MBC). It has been hypothesized that bevacizumab could modify CTC prognostic value. CEC variations to predict benefit of anti-angiogenic treatment is still controversial. Predictive markers for response to bevacizumab combined to chemotherapy in MBC remains a clinical unmet need.
Patients & methods: The French cohort COMET is a prospective study including first line HER2 negative patients (pts) receiving weekly paclitaxel and bevacizumab according to EMA approved combination. The aim of this cohort is to evaluate clinical, biological and radiological parameters associated with pts outcome (CTC, CEC, serum markers, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). We present here the first planned analysis on 203 pts evaluated for CTC and CEC using the FDA cleared CellSearch method.
Results: For CTC substudy, 211 patients were included from 09/2012 to 5/2014. Median follow-up is 24 months. Median PFS was 10 months (CI95 9-12) and response rate was 57%. Median OS was not reached. 203 patients were evaluable for both CTC and CEC at baseline and first day of second cycle of CT (D1C2). At baseline, 97/203 (48%) pts had ≥ 5 CTC (median 4 (range 0-30,000). Median number CEC was 21 (0-2231) at baseline and 22 (1-881) at D1C2. LDH, CEA, CA15.3 and CYFRA 21 were above normal at baseline in 44%, 46%, 73% and 71% of the cases respectively. CTC level was not correlated with any patients' characteristics except a number of metastatic site &gt;3. After one cycle of chemotherapy (D1C2) 37 pts (22%) had still ≥ 5 CTC: 36 pts with initial high level and only one patient with low CTC at baseline had increased CTC above 5. Prognostic factors for PFS at univariate analysis were visceral disease, number of metastatic sites (&gt; 3), triple negative status, LDH, CTC level at baseline and CTC level after one cycle of chemotherapy (D1C2). None of serum marker nor CEC level at baseline or any variations had prognostic value. In multivariate analysis for PFS, CTC level after one cyle of chemotherapy predicts poor outcome
Table 1 Multivariate analysis for PFSPts' characteristicsnRRCI 95%p-valueNumber of metastatic sites &lt;3 sites971 &gt;=3 sites1001.65[1.13 ; 2.41]0.010CTC D1C2 &lt; 51321 &gt;= 5372.17[1.43 ; 3.29]&lt;0.001Hormonal status Luminal (HR+)1531 Triple negative372.86[1.85 ; 4.54]&lt;0.001
Conclusion: We confirm in a large prospective series the lack of clinical validity of CEC to predict response to an antiangiogenic based treatment in MBC. A persistent elevated level of CTC after just one cycle of chemotherapy is a very strong and independent marker of poor outcome in a homogeneously bevacizumab-treated cohort of MBC patients. This marker could be used to stopped earlier an inefficient and costly treatment.
Citation Format: Pierga J-Y, Tredant O, Chevrier M, Dubot C, Lorgis V, Romieu G, Goncalves A, Debled M, Levy C, Ferrero J-M, Jouannaud C, Luporsi E, Mouret-Reynier M-A, Dalenc F, Berger F, Lemonnier J, Proudhon C, Bidard F-C. Circulating tumor cells (CTC) and endothelial cells (CEC) prognostic value in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab: First results of a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-02.