Impact of cholangiocarcinoma (CC) molecular heterogeneity on outcome during first-line chemotherapy and access to targeted therapies in early clinical trials (CT).

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 4091-4091
Author(s):  
Helena Verdaguer ◽  
Irene Brana ◽  
Cinta Hierro ◽  
Analia Azaro ◽  
Elena Elez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapies ◽  
Molecular Heterogeneity ◽  
First Line ◽  
Line Chemotherapy

Progression-free survival (PFS) as a surrogate end point for overall survival (OS) in first-line treatment of advanced epithelial ovarian cancer (EOC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5081-5081 ◽  
Author(s):  
Katrin Marie Sjoquist ◽  
Chee Lee ◽  
Sally Lord ◽  
Mark D. Chatfield ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Effect ◽  
Gynecological Cancer ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Least Square ◽  
First Line ◽  
End Point ◽  
Platinum Based Chemotherapy ◽  
Line Chemotherapy

5081 Background: The duration and cost of clinical trials of first-line chemotherapy in advanced EOC could be reduced if a surrogate endpoint were used in place of OS. The consensus of the Gynecological Cancer Intergroup was that PFS is the preferred primary end point for these trials due to potential confounding of post-progression therapy on OS. We performed a systematic review to assess the extent to which treatment effect on PFS is predictive of OS in this patient population. Methods: Randomised trials of first-line chemotherapy comparing platinum containing regimens in advanced EOC were identified; trials with non-platinum backbone, maintenance strategies or biological containing therapies were excluded. Summary data (hazard ratios (HR), median PFS and OS and the ratios of medians between treatment arms) were extracted. Weighted least-square (WLS) R2 by trial sample size derived using linear regression was used to report correlation. Results: 15 eligible trials with 19 treatment comparisons were identified comprising a total of 16,598 patients. There was a good correlation between treatment effect on PFS and OS (correlation of HR: r, 0.88, WLS R2, 0.71; correlation of ratios of medians: r, 0.84, WLS R2, 0.72). Good correlation between treatment effect on PFS and OS was also observed in various prognostic subgroups (Table). Conclusions: In clinical trials of first-line platinum based chemotherapy without biological agents in advanced EOC, treatment effect on PFS and OS is highly correlated. PFS could be considered as a primary end point when evaluating future first line strategies in advanced EOC. [Table: see text]

scholarly journals Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 183-191
Author(s):  
Yuankai Lv ◽  
Zhuo Cao ◽  
Jiongwei Pan ◽  
Enhui Gong ◽  
Hao Zheng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
First Line ◽  
Randomized Controlled Clinical Trials ◽  
Line Chemotherapy

Abstract Objective The aim of the present work was to investigate the clinical efficacy of first-line chemotherapy regimens in the treatment of advanced non-small cell lung cancer (NSCLC) through a comprehensive network meta-analysis (NMA). Methods The prospective randomized controlled clinical trials relevant to 10 first-line chemotherapy regimens in the treatment of advanced NSCLC were systematic electronic search in the databases of Pubmed, Embase, Cochrane Library and CNKI. The combined direct or indirect objective response rate (ORR) between each of the 10 first-line chemotherapy regimens was calculated. Results Seventeen prospective clinical trials of first-line chemotherapy regimens in treatment of advanced NSCLC were included in the NMA. The 10 treatment regimens including A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = docetaxel + carboplatin, G = gemcitabine + vinorelbine, H = pemetrexed + carboplatin, I = cisplatin + pemetrexed and J = cisplatin + docetaxel were compared in the present NMA. Direct pooled results indicated that the ORR was not statistically different (P all > 0.05). However, NMA showed that the combined ORR for regimens A (OR = 1.47, 95% CI: 0.80–2.81), B (OR = 3.22, 95% CI: 1.45–6.923), D (OR = 3.30, 95% CI: 1.22–9.33), E (OR = 4.36, 95% CI: 1.64–12.82), G (OR = 3.72, 95% CI: 1.12–12.83) and I (OR = 5.80, 95% CI: 2.04–17.86) was superior to regimen C. Rank probability analysis indicated that regimen C = gemcitabine and regimen I = cisplatin + pemetrexed had the highest probability of inferior and superior treatment ORR among the 10 first-line chemotherapy regimens. Conclusion Cisplatin + pemetrexed may have particularly prominent ORR for advanced NSCLC as the first-line chemotherapy regimen.

Esophageal Cancer: A Critical Evaluation of Systemic Second-Line Therapy

2011 ◽  
Vol 29 (35) ◽  
pp. 4709-4714 ◽  
Author(s):  
Christiane Maria Rosina Thallinger ◽  
Markus Raderer ◽  
Michael Hejna
Keyword(s):  
Esophageal Cancer ◽  
Targeted Therapies ◽  
Single Agent ◽  
Critical Evaluation ◽  
Individual Therapy ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Line Chemotherapy

The objective of this article was to review clinical trials that used antineoplastic second-line chemotherapy and/or targeted therapies in patients with esophageal cancer after first-line therapy. Computerized (MEDLINE) and manual searches were performed to identify articles published on this topic between 1996 and 2011. Twenty-five published trials and four abstracts presented at scientific meetings were identified. A total of 10 trials included only patients with squamous cell carcinomas (SCCs), four focused exclusively on adenocarcinoma (AC), the remaining 15 studies included both SCC and AC. The majority of trials (17 of 29) used docetaxel in combination with platinum analogs, eight used single-agent cytotoxic chemotherapy, and six evaluated targeted therapies. The numbers of patients were relatively small, ranging from eight to 55 patients. The response rates were generally low (between 0% and 39%), with only two small studies reporting objective responses of 50% and 63%, respectively. Time to progression ranged from 1.4 to 6.2 months, and the overall survival was disappointing at 4.0 to 11.4 months. Approximately 40% of patients who experience progressive disease after first-line chemotherapy are able to undergo second-line treatment. On the basis of data published so far, no standard second-line therapy has emerged. Future research will need to focus on individual therapy strategies such as genetic receptor mutations to increase the therapeutic outcome.

scholarly journals Chemotherapy plus bevacizumab as an optimal first-line therapeutic treatment for patients with right-sided metastatic colon cancer: a meta-analysis of first-line clinical trials

ESMO Open ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. e000605 ◽  
Author(s):  
Xia-Hong You ◽  
Yu-Huan Jiang ◽  
Zhou Fang ◽  
Fan Sun ◽  
Yao Li ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Growth Factor ◽  
Targeted Therapies ◽  
Meta Analysis ◽  
Survival Ratio ◽  
Metastatic Colon Cancer ◽  
Wild Type ◽  
First Line ◽  
Metastatic Setting ◽  
The Right

BackgroundMonoclonal antibodies of anti-epidermal growth factor receptor (EGFR) have been recommended as first-line therapy for patients with left-sided metastatic colorectal cancer (mCRC) with wild-type RAS. The effect of tumour laterality on antivascular endothelial growth factor antibody and how to optimise targeted therapies for the right-sided cases remain controversial.Patients and methodsA comprehensive meta-analysis enrolling 16 first-line clinical trials was performed to evaluate the efficacy of chemotherapy alone and chemotherapy plus targeted therapies for patients with mCRC with right primary tumour site, and we validated the results in metastatic setting (14 trials containing 4306 patients with unresectable mCRC).ResultsHere, we found that progression-free survival (PFS) (combined HR 1.30, 95% CI 1.17 to 1.44) and overall survival (OS) (combined HR 1.46, 95% CI 1.32 to 1.62) of the right-sided patients were significantly inferior to the left-sided individuals receiving chemotherapy alone in overall population, regardless of race. Similar results were also observed in metastatic setting. OS of patients with left-sided mCRC receiving chemotherapy plus bevacizumab was superior to the right-sided individuals (combined median survival ratio (MSR)=1.23, 95% CI 1.08 to 1.39 for overall population; combined MSR=1.23, 95% CI 1.05 to 1.45 for metastatic setting), especially for wild-type RAS and mixed population. Moreover, the right-sided patients benefited more from chemotherapy plus bevacizumab comparing with chemotherapy alone in both overall population and metastatic setting. Importantly, the RAS-wild right-sided patients achieved longer PFS (combined HR 0.67, 95% CI 0.52 to 0.88) and OS (combined HR 0.74, 95% CI 0.56 to 0.98) from chemotherapy plus bevacizumab comparing with chemotherapy associated with anti-EGFR agents.ConclusionsPatients with right-sided mCRC show impaired chemosensitivity, and chemotherapy plus bevacizumab can be an optimal first-line therapeutic regimen for the RAS-wild patients with right-sided mCRC.

scholarly journals A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1795
Author(s):  
Elisabete Cruz Da Silva ◽  
Marie-Cécile Mercier ◽  
Nelly Etienne-Selloum ◽  
Monique Dontenwill ◽  
Laurence Choulier
Keyword(s):  
Clinical Trials ◽  
Targeted Therapies ◽  
Standard Treatment ◽  
Cell Metabolism ◽  
Tyrosine Kinase Receptors ◽  
Newly Diagnosed ◽  
Glial Tumor ◽  
First Line ◽  
The Mean ◽  
And Migration

Glioblastoma (GBM), the most frequent and aggressive glial tumor, is currently treated as first line by the Stupp protocol, which combines, after surgery, radiotherapy and chemotherapy. For recurrent GBM, in absence of standard treatment or available clinical trials, various protocols including cytotoxic drugs and/or bevacizumab are currently applied. Despite these heavy treatments, the mean overall survival of patients is under 18 months. Many clinical studies are underway. Based on clinicaltrials.org and conducted up to 1 April 2020, this review lists, not only main, but all targeted therapies in phases II-IV of 257 clinical trials on adults with newly diagnosed or recurrent GBMs for the last twenty years. It does not involve targeted immunotherapies and therapies targeting tumor cell metabolism, that are well documented in other reviews. Without surprise, the most frequently reported drugs are those targeting (i) EGFR (40 clinical trials), and more generally tyrosine kinase receptors (85 clinical trials) and (ii) VEGF/VEGFR (75 clinical trials of which 53 involving bevacizumab). But many other targets and drugs are of interest. They are all listed and thoroughly described, on an one-on-one basis, in four sections related to targeting (i) GBM stem cells and stem cell pathways, (ii) the growth autonomy and migration, (iii) the cell cycle and the escape to cell death, (iv) and angiogenesis.

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