CabaGast: multicentre, Phase II study with cabazitaxel in previously treated patients with advanced or metastatic adenocarcinoma of the esophagogastric junction and stomach

This is a single-arm study (NCT01956149) to determine the prolonged (4 months) disease control rate with cabazitaxel administered in second-(or later) setting for patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (EGJ) and stomach. 65 patients with advanced EGJ and stomach cancer were treated with 20 mg/m(2) cabazitaxel every 3 weeks for a maximum of six cycles. The main objective of the study is a prolonged disease control rate (pDCR: CR, PR or SD lasting at least 4 months). Secondary outcome measures were overall survival, progression-free survival, response rate by subgroup (with vs without previous treatment with a taxane) and toxicity. Patients were assessed for tumor response every 6 weeks during therapy and during the follow-up (up to 12 months). 65 patients (median age: 63, range 31-86 years) were assigned to treatment. Median no. of prior therapies that had received prior taxane therapy was 2. 80%. Patients received a median of two cycles of cabazitaxel. Efficacy results are for the ITT population. The mDCR in n = 65 patients was 10.8% (95% CI 4.4-20.9%). There was a control of disease (CR + PR + SD) in n = 26 patients of n = 65, corresponding to a DCR of 40.0% (95% CI 28.0-52.9%). In patients without prior taxane use, it was 46.2% (95% CI 25.1-80.8%) and in patients with only one prior therapy, DCR was 50.0% (95% CI 31.3-68.7%). The median overall survival was 4.6 months (95% CI 3.16, 5.59) in the whole ITT population. In patients with only one prior therapy, median OS was 5.4 months (95% CI 2.60, 7.43) and in patients without taxane pretreatment, it was 6.4 months (95% CI 1.38, 14.17). The median progression-free survival time was 1.5 months (95% CI 1.32, 2.27) in the whole ITT population, 2.9 months (95% CI 0.72, 4.67) without prior taxane therapy and was 1.7 (95% CI 1.28, 3.35) months in patients with only one prior therapy median. Cabazitaxel is active in heavily pretreated patients with metastatic and advanced esophagogastric junction and gastric adenocarcinoma. Efficacy results in a classic second-line population are comparable to other second-line studies, therefore, under the limitations of this trial, (single arm, Phase II design) cabazitaxel might be an option especially in patients without prior taxane therapy, in second line and even further line therapy of metastatic and advanced esophagogastric junction and gastric adenocarcinoma

CabaGast: multicentre, Phase II study with cabazitaxel in previously treated patients with advanced or metastatic adenocarcinoma of the esophagogastric junction and stomach

This is a single-arm study (NCT01956149) to determine the prolonged (4 months) disease control rate with cabazitaxel administered in second-(or later) setting for patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (EGJ) and stomach. 65 patients with advanced EGJ and stomach cancer were treated with 20 mg/m(2) cabazitaxel every 3 weeks for a maximum of six cycles. The main objective of the study is a prolonged disease control rate (pDCR: CR, PR or SD lasting at least 4 months). Secondary outcome measures were overall survival, progression-free survival, response rate by subgroup (with vs without previous treatment with a taxane) and toxicity. Patients were assessed for tumor response every 6 weeks during therapy and during the follow-up (up to 12 months). 65 patients (median age: 63, range 31-86 years) were assigned to treatment. Median no. of prior therapies that had received prior taxane therapy was 2. 80%. Patients received a median of two cycles of cabazitaxel. Efficacy results are for the ITT population. The mDCR in n = 65 patients was 10.8% (95% CI 4.4-20.9%). There was a control of disease (CR + PR + SD) in n = 26 patients of n = 65, corresponding to a DCR of 40.0% (95% CI 28.0-52.9%). In patients without prior taxane use, it was 46.2% (95% CI 25.1-80.8%) and in patients with only one prior therapy, DCR was 50.0% (95% CI 31.3-68.7%). The median overall survival was 4.6 months (95% CI 3.16, 5.59) in the whole ITT population. In patients with only one prior therapy, median OS was 5.4 months (95% CI 2.60, 7.43) and in patients without taxane pretreatment, it was 6.4 months (95% CI 1.38, 14.17). The median progression-free survival time was 1.5 months (95% CI 1.32, 2.27) in the whole ITT population, 2.9 months (95% CI 0.72, 4.67) without prior taxane therapy and was 1.7 (95% CI 1.28, 3.35) months in patients with only one prior therapy median. Cabazitaxel is active in heavily pretreated patients with metastatic and advanced esophagogastric junction and gastric adenocarcinoma. Efficacy results in a classic second-line population are comparable to other second-line studies, therefore, under the limitations of this trial, (single arm, Phase II design) cabazitaxel might be an option especially in patients without prior taxane therapy, in second line and even further line therapy of metastatic and advanced esophagogastric junction and gastric adenocarcinoma

Prognostic Role of Circulating Tumor Cells during Induction Chemotherapy Followed by Curative Surgery Combined with Postoperative Radiotherapy in Patients with Locally Advanced Oral and Oropharyngeal Squamous Cell Cancer

<div><p>Background</p><p>The prognostic role of circulating tumor cells (CTCs) after induction chemotherapy using docetaxel, cisplatin and fluorouracil (TPF) prior to surgery and adjuvant (chemo)radiation in locally advanced oral squamous cell cancer (OSCC) was evaluated.</p><p>Methods</p><p>In this prospective study, peripheral blood samples from 40 patients of the phase II study TISOC-1 (NCT01108042) with OSCC before, during, and after treatment were taken. CTCs were quantified using laser scanning cytometry of anti– epithelial cell adhesion molecule–stained epithelial cells. Their detection was correlated with clinical risk factors, recurrence-free (RFS) and overall survival (OS).</p><p>Results</p><p>Before starting the treatment CTCs were detected in 32 of 40 patients (80%). The median number at baseline was 3295 CTCs/ml. The median maximal number of CTCs during treatment was 5005 CTCs/ml. There was a significant increase of CTCs before postoperative radiotherapy compared to baseline before 1^st cycle of IC (p = 0.011), 2^nd cycle of IC (p = 0.001), 3^rd cycle of IC (p = 0.004), and before surgery (p = 0.002), but not compared to end of therapy (p = 0.118). CTCs at baseline >median was also associated to risk of recurrence (p = 0.014). Maximal CTCs during therapy >median was more frequently observed in tumors of the oral cavity (p=0.022) and related to higher risk of death during follow-up (p = 0.028). Patients with CTCs at baseline >median value had significant lower RFS than patients with CTCs at baseline median during the complete course of therapy had a significantly lower OS than patients with values </p><p>Conclusions</p><p>Baseline CTCs and maximal CTCs during therapy both seem to be good prognostic markers for OSCC when treated by TPF induction chemotherapy, surgery, and postoperative (chemo)radiation.</p></div

Univariate analysis (log-rank test) of negative prognostic parameters influencing recurrence-free survival (RFS) and overall survival (OS).

<p>CR = complete response; IC = induction chemotherapy</p><p>Univariate analysis (log-rank test) of negative prognostic parameters influencing recurrence-free survival (RFS) and overall survival (OS).</p

Kaplan-Meier curves on recurrence-free survival (A, B) and overall survival (C, D) according to therapy arm (A, C), circulating tumor cells (CTCs) at baseline (B), and maximal amount of CTCs during the treatment.

<p>Kaplan-Meier curves on recurrence-free survival (A, B) and overall survival (C, D) according to therapy arm (A, C), circulating tumor cells (CTCs) at baseline (B), and maximal amount of CTCs during the treatment.</p

Circulating tumor cells (CTCs) during TISOC1 treatment.

<p>Circulating tumor cells (CTCs) during TISOC1 treatment.</p

Clinicopathologic characteristics.

<p>Clinicopathologic characteristics.</p

Treatment characteristics.

<p>*all surgeries were performed R0.</p><p>Treatment characteristics.</p

Univariate analysis (log-rank test) of negative prognostic parameters influencing recurrence-free survival (RFS) and overall survival (OS).

<p>CR = complete response; IC = induction chemotherapy</p><p>Univariate analysis (log-rank test) of negative prognostic parameters influencing recurrence-free survival (RFS) and overall survival (OS).</p