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The cross-over analysis of the SHIVA trial identified 37% of patients who crossed-over from TPC to MTA with a PFSMTA/PFSTPC ratio exceeding 1.3.

Background:The SHIVA trial is a multicentric randomised proof-of-concept phase II trial comparing molecularly targeted therapy based on tumour molecular profiling vs conventional therapy in patients with any type of refractory cancer. Results of the feasibility study on the first 100 enrolled patients are presented.Methods:Adult patients with any type of metastatic cancer who failed standard therapy were eligible for the study. The molecular profile was performed on a mandatory biopsy, and included mutations and gene copy number alteration analyses using high-throughput technologies, as well as the determination of oestrogen, progesterone, and androgen receptors by immunohistochemistry (IHC).Results:Biopsy was safely performed in 95 of the first 100 included patients. Median time between the biopsy and the therapeutic decision taken during a weekly molecular biology board was 26 days. Mutations, gene copy number alterations, and IHC analyses were successful in 63 (66%), 65 (68%), and 87 (92%) patients, respectively. A druggable molecular abnormality was present in 38 patients (40%).Conclusions:The establishment of a comprehensive tumour molecular profile was safe, feasible, and compatible with clinical practice in refractory cancer patients.

Background: Several prognostic factors and composite scores based on either patients general condition and/or usual blood analyses have been described in the setting of advanced metastatic cancers to estimate patients overall survival (OS). Over the past decade, circulating tumor cells (CTC) have been repeatedly reported as being a strong prognostic tool in metastatic breast cancer patients. We took the opportunity of the observational part of a prospective clinical trial (CirCe01, NCT01349842) that included 3rd line metastatic breast cancer patients to assess and compare several prognostic factors/scores and circulating tumor cell count. Patients and Methods: Metastatic breast cancer patients were included before the start of a 3rd line chemotherapy at the Institut Curie, Paris, France. The following adverse prognostic factors were assessed prospectively and compared to overall survival: altered performance status (PS≥2), lymphopenia (<1,000 lymphocyte/microl), elevated CTC count (CellSearch, ≥5CTC/7.5ml), low albumin (<35g/l), elevated CA 15.3 (>30UI/ml), elevated CEA (>5ng/ml), elevated LDH (>50UI/l). Two composite scores were also evaluated: the Barbot score (combining Karnofsky index, number of metastases, albumin and LDH; Barbot JCO 2008) and the Prognostic Inflammatory and Nutritional Index (PINI; combining albumin, prealbumin, orosomucoid and C-reactive protein). Metastatic sites (liver, lung, bone) were also analyzed. Survival was analyzed by Kaplan-Meier curves; multivariate analysis was done using a Cox model. Results: 56 patients have included prospectively and 36 of them (64%) died. CA 15.3 and CEA levels, lymphopenia and metastatic sites had no significant impact on OS in univariate analysis. The incidence of the significant prognostic markers (%), their correlations (p value) and impact (p value) on overall survival are shown. Correlation and impact on overall survival of prognostic markersFactorIncidenceCorrel. with PS (p value)Correl. with Alb (p value)Correl. with LDH (p value)Correl. with Barbot (p value)Correl. with PINI (p value)Univ. OS (p value)CTC > = 545%NSNS<0.001NSNS0.004PS > = 214%-0.0020.04<0.0010.003<0.001Alb <3516%--NS<0.001<0.001<0.001LDH>50065%---0.05NS0.032Barbot score >316%----0.005<0.001PINI >1013%-----<0.001 In multivariable analysis, the three independent prognostic markers on OS were: elevated CTC count (p = 0.003, HR = 3.4 95% CI [1.5-7.7]), poor PS (p = 0.005, HR = 4.1 95% IC[1.5-11.3]) and low albumin (p<0.0001, HR = 11.3 95% IC[3.9-32.5]). Discussion: CTC are an independent prognostic marker, even in advanced metastatic breast cancer. The disease aggressiveness being captured by the CTC count, usual clinical and biochemical tests appear to be sufficient to evaluate the patient prognosis, whereas more complex score (PINI, Barbot) appear to be of low interest. Financed by: Ligue contre le cancer and PHRC 2009. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-16.

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