scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

scholarly journals Patient-reported outcomes in clinical trials

2016 ◽  
Vol 4 (2) ◽  
pp. 54-58
Author(s):  
Florence Joly ◽  
Gloria Mittica
Keyword(s):  
Clinical Trials ◽  
Health Care Professionals ◽  
Patient Reported Outcomes ◽  
Specific Treatment ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Treatment Benefit ◽  
Free Survival ◽  
Disease Response ◽  
Patient Reported

Patient-reported outcomes (PROs) are progressively being included in clinical trials to provide information about treatment benefits identified by the patients themselves that extend the data on traditional clinical trial endpoints, such as disease free survival, overall survival, progression-free survival, and response rate. PROs may have a greater impact for patients than other endpoints. For example, patients may be prepared to forgo some increase in progression-free survival in return for reduced treatment-related toxicity. PROs may also be an indicator of disease response and have value as prognostic factors. This article discusses the way PROs can be defined and incorporated into clinical trials to enhance the value of clinical trials data and improve the understanding of the clinical benefits of a specific treatment, not only for health care professionals, but for patients and caregivers. The importance and relevance of a patient-centered perspective and shared decision making in defining value and determining treatment benefit is increasingly recognized. However, despite the acknowledged value of PROs, their inclusion in clinical trials remains far from ideal. New guidelines from the research community and technological improvements in data collection and analytics will increase the quality and the importance of PROs as standard methods for the evaluation of medical studies and in the drugs approval process.

Clinical implications of polymorphisms in UDP-glucuronosyl transferase (UGT) in patients with metastatic colorectal cancer (mCRC) who were treated with oxaliplatin, irinotecan, and S-1.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 503-503
Author(s):  
Sun Young Kim ◽  
Mi Song I Jang ◽  
Hyun Mi Kim ◽  
Ji Yeon Baek ◽  
Yong Sang Hong ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Regimen ◽  
High Rate ◽  
Free Survival ◽  
Effective Therapeutic Option ◽  
Glucuronosyl Transferase ◽  
Intensive Regimen ◽  
Selection Of

503 Background: The three-drug regimen with oxaliplatin, irinotecan and fluoropyrimidine is an effective therapeutic option for patients with mCRC, but is associated with high rate of toxicity. Pharmacogenetic profile might be helpful for selection of proper patients for this intensive regimen. Methods: Forty-two patients were enrolled to our phase II trial and were given irinotecan 150mg/m2 plus oxaliplatin 85mg/m2 on D1 and S-1 80mg/m2/day on D1-14 every 21 days as their front-line therapy for mCRC. Genomic DNA was extracted from peripheral blood, where the presence of germline polymorphisms of UGT including UGT1A1*6, UGT1A1*28, UGT1A1*60, UGT1A6*2, and UGT1A7*3 were tested. Results: Patients with UGT1A1*6 allele had a tendency of more frequent grade 2-3 vomiting (p = 0.06) compared to those without UGT1A1*6. The presence of a haplotype containing UGT1A6*2 and UGT1A7*3 was associated with grade 2-3 vomiting (p = 0.014) and grade 2-3 diarrhea (p = 0.063). Higher objective response rate (18/20, 90%) was noted in patients without UGT1A*60 compared to those with UGT1A1*60 (11/22, 50%; p = 0.008). The absence of UGT1A1*60 was also associated with marginally improved progression-free survival (10.3 mo v 7.7 mo, p = 0.081) and overall survival (26.8 mo v 15.1 mo, p= 0.044) compared to the presence of the variant allele. Conclusions: UGT1A1*6 and a haplotype containing UGT1A6*2 and UGT1A7*3 may be associated with irinotecan-related gastrointestinal toxicities. Phenotypic association of UGT1A1*60 and efficacy of the three-drug regimen requires further investigation.

Correlation between overall response rate and progression-free survival/overall survival in comparative trials involving targeted therapies in molecularly enriched populations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3588-3588
Author(s):  
Benjamin J. Solomon ◽  
Herbert H. F. Loong ◽  
Yvonne J. Summers ◽  
Zachary M Thomas ◽  
Pearl Plernjit French ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Response Rate ◽  
Pearson Correlation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Targeted Agents ◽  
Free Survival ◽  
Comparative Trials

3588 Background: Randomized trials involving agents targeting oncogene addicted tumors have greatly increased over the past decade. Whether clinical response rates can predict or correlate with efficacy measures such as progression-free survival (PFS) or overall survival (OS) has not been established in molecularly enriched patient populations. In this meta-analysis, we investigated whether improvements in objective response rate (ORR) in comparative trials using targeted agents could serve as a potential surrogate endpoint for improvements in PFS or OS in populations with oncogene addicted cancer. Methods: CT.gov and MEDLINE databases were queried (using commercial text mining software I2E) for randomized, phase 3 clinical trials based on the following prospectively defined criteria: (1) use of agents targeting EGFR activating mutations (erlotinib, gefitinib, afatinib, dacomitinib, osimertinib), ALK and ROS1 rearrangements (crizotinib, ceritinib, alectinib), BRAF V600E or V600K mutations (dabrafenib), and BCR-ABL fusion protein (imatinib, dasatinib, nilotinib, ponatinib); (2) must include molecularly enriched trial populations (biomarker subgroup data included if available); (3) control arms should not include targeted agents directed towards those molecularly enriched populations. ORR, OS, and PFS data were manually extracted from the relevant studies and correlative analyses (weighted Pearson correlation) were performed. Results: 61 trials were identified with 15 ultimately meeting the prespecified criteria. ORR effect size (both the ORR difference and log odds ratio) and the log PFS hazard ratio were strongly correlated (-0.78, p-value = 0.0007). No significant correlation was found between ORR and OS. Conclusions: In our analyses, a strong correlation between ORR and PFS was found in randomized clinical trials investigating agents targeting oncogene-driven cancers. Establishing a correlation between ORR and OS was limited, most probably due to confounding factors such as treatment cross-over following progression, number of subsequent therapies and long post-progression survival in this setting. These findings further warrant the use of ORR as a surrogate for PFS in biomarker-driven studies.

scholarly journals Anlotinib combined with SOX regimen (S1 (tegafur, gimeracil and oteracil porassium capsules) + oxaliplatin) in treating stage IV gastric cancer: study protocol for a single-armed and single-centred clinical trial

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e034685 ◽  
Author(s):  
Juan Wang ◽  
Dong Xue Wu ◽  
Lu Meng ◽  
Gang Ji
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Iv Gastric Cancer ◽  
Before And After

IntroductionAnlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy in some solid tumours. However, evidence on the safety and feasibility of anlotinib in patients with stage IV gastric cancer is scarce.Methods and analysisThis study is a single-armed and single-centred clinical study being designed to include 150 patients of stage IV gastric cancer. The patients’ demographics, pathological characteristics, test results of blood, biochemistry and tumour markers before and after medication, disease-free survival and overall survival will be collected and analysed. The primary and main efficacy outcomes are objective response rate, progression-free survival, disease control rate and overall survival. The secondary efficacy outcome is safety indicator including the incidence of adverse drug reactions and adverse events after administration.Ethics and disseminationEthics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20192111-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.Trial registration numberChiCTR1900026291 (registration date: 29 September 2019).

scholarly journals Overall Survival Versus Progression-Free Survival in Oncology Clinical Trials

2016 ◽  
Vol 19 (7) ◽  
pp. A717 ◽  
Author(s):  
A Aissaoui ◽  
A Bin Sawad ◽  
F Turkistani ◽  
N Aissaoui
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Progression Free Survival ◽  
Free Survival ◽  
Oncology Clinical Trials

scholarly journals Use of first-line trabectedin in advanced leiomyosarcoma: a review of clinical data and future perspectives

2016 ◽  
Vol 4 (1) ◽  
pp. 6-10
Author(s):  
Nadia Hindi ◽  
Florence Duffaud ◽  
Giacomo Giulio Baldi ◽  
Patricia Pautier
Keyword(s):  
Clinical Trials ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Large Subgroup ◽  
Myxoid Liposarcomas ◽  
Line Setting

Leiomyosarcomas (LMS) represent a large subgroup of soft-tissue sarcoma (STS) generally considered moderately sensitive to conventional chemotherapy. Single-agent doxorubicin is the standard first-line therapy for advanced non-selected STS, although combination with ifosfamide appears to be superior in terms of objective response. Gemcitabine-based regimes, dacarbazine, trabectedin and pazopanib seem to be especially active in patients with advanced LMS, while the activity of ifosfamide in this histotype is low. Data derived from clinical trials and retrospective series show that trabectedin is especially active in L-sarcomas including non-gynecological and uterine LMS as well as liposarcomas, in particular myxoid liposarcomas. Trabectedin has also been tested in the first-line setting, alone or in combination with doxorubicin, for the treatment of LMS of uterine and non-uterine origin in a trial by the French Sarcoma Group (phase II study LMS-02) with encouraging results in terms of median progression-free survival and objective response. The toxicity profile of trabectedin appears to be comparable to, or even more manageable than, that of other chemotherapy combinations in the first-line setting. Designing new clinical trials based on specific histologic subtypes is feasible, and the results of such studies would help to optimize the management of patients with STS.

scholarly journals Immunotherapy for Prostate Cancer: Biology and Therapeutic Approaches

2011 ◽  
Vol 29 (27) ◽  
pp. 3677-3685 ◽  
Author(s):  
Edward Cha ◽  
Lawrence Fong
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Immune System ◽  
Cancer Biology ◽  
Objective Response ◽  
Progression Free Survival ◽  
Therapeutic Approaches ◽  
Free Survival ◽  
Randomized Controlled ◽  
The Past

Although prostate cancer was not historically considered to be a particularly immune-responsive cancer, recent clinical trials have demonstrated that immunotherapy for prostate cancer can lead to improvements in overall survival (OS). These studies include randomized controlled trials with sipuleucel-T and another with PROSTVAC-VF, both of which rely on stimulating the immune system to target prostate proteins. This review discusses the most promising developments over the past year in immune-based therapy for prostate cancer and the opportunities that lie ahead. Recent randomized immunotherapy trials in prostate cancer have demonstrated improvements in OS but without the concomitant improvements in progression-free survival. This uncoupling of survival from clinical response poses challenges to clinical management, because conventional measures of objective response cannot be used to identify patients benefiting from treatment. There is a significant need to identify immunologic or clinical surrogates for survival so that clinical benefit can be assessed in a timely manner. Immunotherapy is now an established treatment approach for prostate cancer, with multiple clinical trials demonstrating improvements in OS. Significant challenges to this modality remain, including determining best clinical setting for immunotherapy, identifying patients who benefit, and defining relevant clinical and immunologic end points. Nevertheless, the broader availability of novel immunotherapies will provide opportunities not only to target different components of the immune system but also to combine immunotherapies with other treatments for improved clinical efficacy.

scholarly journals Physicians’ Perception of the Evidence in Relation to Primary Endpoints of Clinical Trials on Breast Cancer

Breast Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Yi Zhang ◽  
Miao Liu ◽  
Houpu Yang ◽  
Shu Wang
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Local Treatment ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Absolute Difference ◽  
Chinese Society ◽  
Free Survival

<b><i>Objective:</i></b> To investigate physicians’ perception of the evidence of clinical trials on breast cancer. <b><i>Methods:</i></b> A survey was conducted by the Chinese Society of Breast Surgeons. We investigated the physicians’ perception of meaningful endpoints, appropriate follow-up duration, and clinically acceptable benefit through online questionnaires. <b><i>Results:</i></b> Among 278 validated questionnaires, the majority of the questions had no consistent answer. For local treatment, 30.6, 28.8, and 28.4% of participants regarded locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) as the most meaningful endpoint, respectively, 47.5% believed that 5-year follow-up can alter clinical practice, and 34.5% thought it should be &#x3e;10 years. In the adjuvant setting, 45.7, 38.5, and 12.9% regarded DFS, OS, and LRR as the most meaningful endpoint, respectively, 52.5% thought that 10-year follow-up was solid, while 37.4% thought that 5-year follow-up was enough. In the advanced setting, 49.6, 24.1, and 23.7% considered progression-free survival, quality of life, and OS the most meaningful endpoint, respectively, and 39.6 and 28.8% considered that a follow-up of 1 year and 3 years, respectively, was meaningful. Similarly, the clinically acceptable absolute difference was inconsistent. <b><i>Conclusion:</i></b> Most Chinese oncologists advocated that surrogate endpoints could be used in certain circumstances, though OS was the most reliable one in breast cancer studies. Doctors’ perceptions of follow-up time and magnitude of benefit vary widely, reflecting the fact that there are many unanswered questions about supporting the use of new cancer treatments; a common understanding needs to be reached, such as a very consensual surrogate endpoint and a meaningful sufficiently large therapeutic benefit.

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