Difference In Disease Control Rate Research Articles

Salvage Therapy of Gemcitabine Plus Endostar Significantly Improves Progression-free Survival (PFS) with Platinum-resistant Recurrent Epithelial Ovarian Cancer

Anti-angiogenic agents have played crucial roles in the treatment of ovarian cancer in recent years, but potential benefits of endostatin have been largely unexplored. The present retrospective study evaluated its efficacy and toxicity with two cohorts of patients with platinum-resistant recurrent ovarian cancer. One cohort received gemcitabine plus endostar (rh-endostatin), and the second cohort received gemcitabine regimen alone, with totals of 31 and 27 patients, respectively. The main endpoints were disease control rate (DCR), PFS, overall survival (OS) and safety. There were statistically significant differences in DCR (70.9% vs. 40.7%; P = 0.02) and PFS (6.3 months vs. 3.2 months, P = 0.001) between the two cohorts. Though the endostar cohort also improved median OS by 2.1 months, there was no statistically significant difference compared with gemcitabine alone cohort in this case (12.5 months vs. 10.4 months, P = 0.201). Treatment was well tolerated for most patients, and toxicity of endostar was negligible. Gemcitabine plus endostar significantly improved the prognosis in patients with platinum-resistant recurrent ovarian cancer, especially in those with malignant effusion. The endostar- containing regimen is recommended in this setting.

A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 peptide vaccine and the combination in patients with previously treated, unresectable stage III or IV melanoma.

4 Background: Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte antigen-4, demonstrated activity in advanced melanoma. Gp100 vaccine showed immunological and clinical responses, and enhanced clinical activity when combined with other immunotherapy. This phase III study compared efficacy and safety of ipilimumab or gp100 monotherapy and combination. Methods: Eligible patients (HLA-A*0201+ previously treated adults with unresectable stage III/IV melanoma) were randomized 1:3:1 to ipilimumab (3 mg/kg q3w x 4 doses) + placebo (n=137), ipilimumab + gp100 (peptides 209-217[210M] and 280-288 [288V]; 1mg q3w x 4 doses; n=403), or gp100 + placebo (n=136). There was no maintenance phase. Primary endpoint was comparison of overall survival (OS) between patients who received combination versus gp100 alone; secondary endpoints were all other OS comparisons, best overall response rate (BORR), disease control rate (DCR) to W24, progression-free survival (PFS), and safety. Results: The study demonstrated statistically significant results for all efficacy endpoints (below). Ipilimumab alone or combined with gp100 resulted in a significant improvement in OS with risk reduction of 32-34% compared to gp100. Significant differences in DCR, BORR, and PFS were observed. Adverse events with ipilimumab were consistent with prior studies: generally mild, immune-related, and medically manageable. Conclusions: Ipilimumab is the first agent to improve median and long-term OS in a phase III study of previously treated patients with advanced melanoma. Addition of gp100 vaccine to ipilimumab did not improve outcome. [Table: see text] [Table: see text]

Abstract 2697: Analysis of the correlation between gene expression of IGF-pathway components and benefit from cetuximab (Erbitux™) in metastatic colorectal cancer patients

Abstract OBJECTIVE: There is considerable evidence showing cross-talk between the epidermal growth factor receptor (EGFR) and insulin-like growth factor-I receptor (IGF-IR) pathways. This analysis was carried out to examine the correlation between the gene expression levels of IGF pathway components and the clinical benefit from the anti-EGFR monoclonal antibody cetuximab in metastatic colorectal cancer (mCRC) patients; and to look for the factors contributing to non-benefit from cetuximab in K-Ras wild type (WT) patients, further seeking the treatment options for this sub-population. EXPERIMENTAL DESIGN: Gene expression profiling data for the components of IGF pathway and K-Ras mutational status are available from 70 pre-treatment tumor biopsies from patients with refractory mCRC receiving cetuximab monotherapy (Khambata-Ford et al., 2007). RESULTS: In this cohort of mCRC, patients with tumors expressing high level of IGF-IR or GRB7 were associated with longer progression-free survival (PFS) with cetuximab than patients with low expression levels of these genes. In addition, patients with tumors that express low level of insulin inducible gene 2 (INSIG2), insulin receptor (INSR), IGF-1 or IGF binding protein 3 (IGFBP3) were found to have a longer PFS and higher disease control rate than patients with high expression levels of these genes. For example, median PFS was 115 days in INSIG2 low-expressing tumors and 58 days in INSIG2 high-expressing tumors (log-rank p=0.0029, hazard ratio=0.45); and the disease control rate was 51.4% and 11.4%, respectively, for patients with INSIG2 low-expressing tumors vs. INSIG2 high-expressing tumors (Fisher exact p=0.0006). Furthermore, among patients with K-Ras WT tumors, a significant difference in disease control rate was observed for INSIG2 low- and high-expressing tumors (76.2 % vs. 18.2 %, Fisher exact p=0.0002). Additionally, patients with K-Ras WT tumors that have a high gene expression of IGF-1R had a significantly higher disease control rate (62.5%) than patients with low expression (26.3%) (Fisher exact p=0.03) and longer PFS (log-rank p= 0.01, hazard ratio=2.45, and median PFS, 122 days vs. 60 days, respectively). CONCLUSION: A statistically significant association was observed between the gene expression of some key components of the IGF pathway and benefit from cetuximab in mCRC. In patients with K-Ras WT tumors, high expression of IGF-1R and GRB7 are potential predictive factors for clinical benefit whereas low expression of IGF-1 and INSIG2 are potential predictive factors for resistance to cetuximab. Our data suggest that IGF pathway plays an important role in benefit from the anti-EGFR therapy cetuximab, and that targeting IGF-1R/IR may prove valuable treatment option in K-Ras WT mCRC patients that not benefit from cetuximab. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2697.

The Analysis of Erlotinib on Brain Metastases in Patients with Non-small-cell Lung Cancer.

Brain metastases are common in non-small-cell lung cancer (NSCLC) and the prognosis is poor. Erlotinib is a specific inhibitor of the epidermal growth factor receptor-associated tyrosine kinase (EGFRTKI), which has been gradually used in the treatment for advanced NSCLC. The aim of this study is to evaluate the antitumor efficacy and its relevant factors of erlotinib in NSCLC patients with brain metastases. The clinical data of 30 NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with erlotinib, given orally 150mg daily. These patients discontinued administration of erlotinib until disease progression, death or intolerable side effects. In terms of intracranial lesions, partial response (PR) was observed in 2 patients (6.7%), with stable disease (SD) in 17 patients (56.7%), for overall disease control rate (DCR) of 63.4%. As for systemic disease, PR was observed in 2 patients (6.7%), with SD in 5 patients (16.7%), for overall DCR of 23.4%. There was no statistical difference in DCR among different subtypes of age, gender, smoking history, histology, PS score, the number of brain metastases, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects. The median time to disease progression (MTTP) and median survival time (MST) was 2.4 months and 7.7 months respectively. The 1 and 2 year survival rate was 38.4% and 15.2%. The univariate analysis showed that the survival time was related to the patients' PS score, smoking history, brain radiotherapy and chemotherapy. The multivariate analysis indicated that brain radiotherapy was the independent prognostic factor and the relationship between the survival time and smoking history was near to statistical significance. The patients receiving brain radiotherapy may have better survival benefit. Non-smokers have a trend to survive longer than smokers. Erlotinib may be effective on brain metastases in NSCLC patients and appears to be a possible new treatment option.

Phase II randomized trial of erlotinib versus vinorelbine in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) aged ≥70 years in Taiwan

8051 Background: Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors, such as erlotinib, are effective against NSCLC, especially in East Asian patients. Single-agent chemotherapy, such as vinorelbine, is an appropriate treatment choice for elderly patients. Oral vinorelbine is more convenient for elderly patients than intravenous vinorelbine. The primary objective of this study was to compare the response rate of chemo-naïve, elderly patients with advanced NSCLC treated with daily erlotinib versus oral vinorelbine. Methods: Chemo-naïve Taiwanese patients aged ≥70 years with advanced NSCLC were enrolled and randomized (stratified by histology, smoking status, ECOG performance status, and gender) to receive either oral erlotinib 150mg/day or oral vinorelbine (60mg/m2 on days 1 and 8 of the first cycle and subsequently increased to 80mg/m2 every 3 weeks in the absence of grade 2 adverse events). From February 2007 to July 2008, 116 patients were enrolled. Results: By October 2008, 77 enrolled patients (n = 37 for erlotinib; n = 40 for vinorelbine) had completed 6 cycles of study treatment and were available for efficacy and safety analyses. Objective response rates were 21.6% (8/37) with erlotinib and 12.8% (5/39) with vinorelbine [95% CI -0.09–0.24 for the difference in response rate between arms]. Disease control rate was 70.3% with erlotinib and 56.4% with vinorelbine [95% CI -0.09–0.34 for the difference in disease control rate between arms; p = 0.216). Median time to disease progression was 4.4 months [95% CI 4.1–5.4] with erlotinib, compared with 3.9 months [95% CI 2.4–6.9] with vinorelbine, p = 0.6069. The most common treatment-related toxicities were skin rash and diarrhea with erlotinib, and diarrhea and nausea with vinorelbine. Conclusions: Erlotinib is effective and well tolerated compared with oral vinorelbine in elderly, chemo-naïve, Taiwanese patients with NSCLC. Updated efficacy and safety data will be presented. [Table: see text]