Eric Levy

A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV non-small cell lung cancer

Background: TG4010 is a recombinant viral vector expressing both the tumor-associated antigen MUC1 and Interleukine-2. This vector is based on the modified virus of Ankara, a significantly attenuated strain of vaccinia virus. TG4010 has been designed to induce or amplify a cellular immune response directed against tumor cells expressing MUC1. Methods: A multicenter, randomized phase II study has explored two schedules of the combination of TG4010 with first line chemotherapy in patients with stage IIIB/IV non-small cell lung cancer. In Arm 1, TG4010 was combined upfront with cisplatin (100 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and day 8). In Arm 2, patients were treated with TG4010 monotherapy until disease progression, followed by TG4010 plus the same chemotherapy as in Arm1. Response rate was evaluated according to RECIST. Median time to progression and median overall survival were calculated according to the Kaplan–Meier method. Results: Sixty-five patients were enrolled, 44 in Arm 1 and 21 in Arm 2, in accordance with the two stage Simon design of the statistical plan. In Arm 1, partial response was observed in 13 patients out of 37 evaluable patients (29.5% of the intent to treat population, 35.1% of the evaluable patients). In Arm 2, two patients experienced stable disease for more than 6 months with TG4010 alone (up to 211 days), in the subsequent combination with chemotherapy, one complete and one partial response were observed out of 14 evaluable patients. Arm 2 did not meet the criteria for moving forward to second stage. The median time to progression was 4.8 months for Arm 1. The median overall survival was 12.7 months for Arm 1 and 14.9 for Arm 2. One year survival rate was 53% for Arm 1 and 60% for Arm 2. TG4010 was well tolerated, mild to moderate injection site reactions, flu-like symptoms, and fatigue being the most frequent adverse reactions. A MUC1-specific cellular immune response was observed in lymphocyte samples from all responding patients evaluable for immunology. Conclusions: The combination of TG4010 with standard chemotherapy in advanced non-small cell lung cancer is feasible and shows encouraging results. A randomized study evaluating the addition of TG4010 to first line chemotherapy in this population is in progress.

Multicenter Study of a Frozen Glove to Prevent Docetaxel-Induced Onycholysis and Cutaneous Toxicity of the Hand

PURPOSE Onycholysis and skin toxicity occur in approximately 30% of patients treated with docetaxel. We investigated the efficacy and safety of an Elasto-Gel (84400 APT Cedex, Akromed, France) frozen glove (FG) for the prevention of docetaxel-induced onycholysis and skin toxicity. PATIENTS AND METHODS Patients receiving docetaxel 75 mg/m2 alone or in combination chemotherapy were eligible for this case-control study. Each patient wore an FG for a total of 90 minutes on the right hand. The left hand was not protected and acted as the control. Onycholysis and skin toxicity were assessed at each cycle by National Cancer Institute Common Toxicity Criteria and documented by photography. Wilcoxon matched-pairs rank test was used. RESULTS Between August 2002 and September 2003, 45 patients were evaluated. Onycholysis and skin toxicity were significantly lower in the FG-protected hand compared with the control hand (P = .0001). Onycholysis was grade (G) 0 in 89% v 49% and G1 to 2 in 11% v 51% for the FG-protected hand and the control hand, respectively. Skin toxicity was G0 in 73% v 41% and G1 to 2 in 27% v 59% for the FG-protected and the control hand, respectively. Median time to nail and skin toxicity occurrence was not significantly different between the FG-protected and the control hand, respectively (106 v 58 days for nail toxicity; 57 v 58 days for skin toxicity). Five patients (11%) experienced discomfort due to cold intolerance. CONCLUSION FG significantly reduces the nail and skin toxicity associated with docetaxel and provides a new tool in supportive care management to improve a patients quality of life.

Matched case‐control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel‐induced onycholysis and cutaneous toxicity of the foot

Onycholysis occurs in approximately 30% of patients treated with docetaxel. The efficacy and safety of an Elasto‐Gel frozen sock (FS) was investigated for the prevention of docetaxel‐induced nail and skin toxicity of the feet.

What is the real impact of bone pain on survival in patients with metastatic hormone‐refractory prostate cancer treated with docetaxel?

To determine the benefit of starting early chemotherapy with docetaxel (the recommended first‐line treatment) for patients with asymptomatic metastatic hormone‐refractory prostate cancer (HRPC).

Neoadjuvant Dose-Dense Gemcitabine plus Docetaxel and Vinorelbine plus Epirubicin for Operable Breast Cancer: Improved Prognosis in Triple-Negative Tumors

AbstractBackground: Neoadjuvant anti-tumor activity of an alternating taxane- and anthracycline-based dose-dense regimen in patients with operable, noninflammatory large breast cancer was investigated. Objective: The objective is to study the rate of pathological complete response in patients with breast cancer receiving dose-dense chemotherapy sequentially with gemcitabine plus docetaxel and vinorelbine plus epirubicin. Methods: Women (n = 74) with clinical stage II or III breast cancer were enrolled in this open-label, multicenter study to receive six 2-weekly courses of gemcitabine 1000 mg/m2 plus docetaxel 75 mg/m2 on days 1 and 15, and vinorelbine 25 mg/m2 plus epirubicin 100mg/m2 on days 29 and 43. Patients with an objective response on day 56 then received another cycle of gemcitabine/ docetaxel on day 57 and of vinorelbine/epirubicin on day 71. Conservative surgery was scheduled for all patients. Results: Of the patients enrolled, 30% had triple-negative breast cancer (TNBC). The pathologic complete response (pCR) rate was 22% overall, but was higher in TNBC than patients without TNBC (40.9% vs 14.0%; p=0.028). Among patients with a pCR, patients with TNBC had similar recurrence-free survival (RFS) and overall survival (OS) to patients without TNBC. Among those without a pCR, RFS rates for patients with TNBC were significantly lower than for patients without TNBC (p=0.04). The most common severe hematologic toxicity was neutropenia. Conclusions: Administering four drugs in a dose-dense alternating sequence gave a high pCR in patients with operable, invasive breast cancer. Patients with TNBC with a pCR had similar OS to patients without TNBC, whereas patients with TNBC without a pCR had poorer survival rate than their non- TNBC counterparts.

Assessment of frozen glove use in the prevention of docetaxel induced onycholysis and cutaneous reaction. Results of a multicenter case-control study

8003 Background: Onycholysis and skin toxicity occur in about 15% of patients (pts) treated with docetaxel (D). We investigated the efficacy and safety of an Elasto-Gel (Akromed, France) flexible frozen glove (FG) for the prevention of D-induced onycholysis and skin toxicity. METHODS Cancer pts receiving D at 75 mg/m2 (1 hour infusion q3w) alone or in combination chemotherapy were eligible for this matched case-control study. Each patient wore a FG for a total of 90 minutes (min) on the right hand (15 min before, during D administration, and 15 min after). The left hand was not protected by FG and acted the control. Onycholysis and skin toxicity were assessed at each cycle by NCI-CTC v.2 criteria and documented by photography. Wilcoxon matched-pairs ranks test was used to determine the magnitude of difference between two matched groups. RESULTS Between Aug 2002 and Sept 2003, 45 pts were evaluated: median age 65 years, M/F: 35/10, performance status 0/1/2 (%) = 52/41/7, cancer type (prostate: 58%, lung: 24%, breast: 11%, others: 7%), D monotherapy 72%. Onycholysis and skin toxicity (main criteria) was significantly lower in the FG protected hand compared with the control hand (p=0.0001, Wilcoxon test). Onycholysis was grade (G)0: 89% vs 49% and G1-2: 11% vs 51% in the FG-protected hand and the control hand, respectively. Skin toxicity was G0: 73% vs. 41% and G1-2: 27% vs. 59% in the FG-protected hand and the control hand, respectively. Median time to nail and skin toxicity occurrence was not significantly different between FG-protected and the control hand, respectively [106 days (5 cycles) vs. 58 days (2.7 cycles) for nail toxicity; 57 days vs. 58 days for skin toxicity]. Five pts (11%) experienced discomfort due to cold intolerance of the FG protected hand. CONCLUSIONS Frozen glove significant reduces the nail and skin toxicity associated with docetaxel and provides a new tool in supportive care management for a better patients quality of life. No significant financial relationships to disclose.

Validation of an expanded neoantigen identification platform for therapeutic and diagnostic use in immuno-oncology.

To assess the e ectiveness of this pipeline in predicting immunogenic neoantigens, we assembled a gold-set of 23 known, previously experimentally-validated immunogenic neoantigens from the literature. We spiked in these neoepitopes into exome data and assessed the ability of our neoantigen pipeline to find and rank these immunogenic known neoantigens. Preliminary results show our neoantigen pipeline is able to accurately identify 22 out of 23 (~96%) of the spiked in neoantigens as being potentially immunogenic. Within our neoantigen pipeline, variants that are detected by our DNA and RNA cancer analysis pipelines are processed for antigen identification, including SNVs, indels, and fusion events. Importantly, both in-frame and out-of-frame events are accurately considered by transcript, allowing for detection of a wealth of candidate neoantigens. Our pipeline includes assessment of important immunologic components including HLA prediction, MHC binding (class I and II), immunogenicity, similarity to self, and similarity to known antigens. Additionally, peptides are evaluated for variant allele frequency in both the RNA and DNA of the tumor sample and gene expression level is considered. Collectively, our ImmunoID product provides a comprehensive assessment of features that may be used for identifying and ranking potentially immunogenic neoantigens. Validation of an Expanded Neoantigen Identification Platform for Therapeutic and Diagnostic Use in Immuno-oncology

Effect of neoadjuvant alternating taxane- and anthracycline-based dose-dense regimen for operable breast cancer on prognosis in triple-negative tumors with a complete histological response.

610 Background: Neoadjuvant antitumour activity of an alternating taxane- and anthracycline-based dose-dense regimen in patients with operable, noninflammatory large breast cancer was investigated. Methods: Women (n = 74) with clinical stage II or III breast cancer were enrolled in this open-label, multicentre study to receive six twice-weekly courses of: gemcitabine 1,000 mg/m2 plus docetaxel 75 mg/m2 on days 1 and 15 and vinorelbine 25 mg/m2 plus epirubicin 100 mg/m2 on days 29 and 43. Patients with an objective response on day 56 then received another cycle of gemcitabine/docetaxel on day 57 and of vinorelbine/epirubicin on day 71. Conservative surgery was scheduled for all patients. Results: Of the patients enrolled, 30% had triple-negative breast cancer (TNBC). Thepathological complete response (pCR) rate was 22% overall, but was higher in TNBC than non-TNBC patients (40.9% versus 14.0%; p = 0.028). Among patients with a pCR, TNBC patients had similar recurrence-free survival (RFS) and overall surviv...