Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer

Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes

Expression génique et puces à ADN (revue et analyse des applications à la cancérologie)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Séminome testiculaire métastatique : analyse descriptive de 18 patients suivis au centre Oscar Lambret entre 1983 et 1998

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Diagnostic and prognostic value of MRI T2 quantificationin heart transplant patients

International audienceThis study was designed retrospectively to assess the value of myocardial T2 to detect or predict ongoing acute heart rejection, in heart transplant patients, with a 1.5-T MRI magnet. One hundred and ninety-six myocardial T2 quantifications were performed on sixty consecutive heart transplant patients during routine follow- up. T2 values were assessed (i) with regard to the results of concomitant biopsies and (ii) with a Cox multivariate model for the prediction of subsequent rejections, defined by a ≥ grade 2 at biopsy or highly suspected in the absence of biopsy (>10% drop in ejection fraction with subsequent reversibility under treatment). T2 values were proposed as main covariate, after logit transformation andadjustment for other confounding parameters such as delay since graft surgery and delay before biopsy. T2 values were strongly linked (i) to the presence of rejection on concomitant biopsy (P < 0.0001) and (ii) to the risk of subsequent rejection on Cox multivariate model (P < 0.001). T2 values above 60 ms were associated with relative risk of rejection higher than 2.0 and rapidly increasing. In conclusion, myocardial T2 yields a high diagnostic and prognostic value for graft rejection in heart transplant patients