Survival among metastatic colorectal patients in clinical trials compared to the real world.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 673-673
Author(s):  
Ziwei Wang ◽  
Lindsay Hwang ◽  
James Don Murphy
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Median Survival ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
The Real ◽  
Clinical Trial Results

673 Background: Randomized clinical trials play a central role in clinical research though only a small fraction of patients partake in clinical studies. Questions thus arise regarding the generalizability of clinical trial results to the remainder of the population. This study evaluated whether patient survival from randomized clinical trials in metastatic colorectal cancer reflects real world outcomes. Methods: A Pubmed search was used to identify randomized phase III clinical trials of first-line treatment for metastatic colorectal cancer published between 2005 and 2010. We excluded secondary or pooled analyses, second-line treatments, non-metastatic patients, non-English language, and non-randomized studies. Thirty-one clinical trials met these criteria, comprised of 79 distinct clinical trial arms. Overall survival among clinical trial patients was compared to metastatic colorectal cancer patients within the Surveillance, Epidemiology, and End Results (SEER) program. Within SEER, we restricted the analysis time-period and age of patients to match the enrollment period and age of patients within each individual clinical trial. Results: The clinical trials enrolled a total of 16,614 patients. Among all clinical trial arms the median survival ranged from 6.7-62 months, 1-year survival ranged from 30-97%, and 2-year survival ranged from 6-88%. Compared to SEER, the median survival was higher in 95% of the individual clinical trial arms by an average of 5.4 months (p<0.0001). The 1-year survival was higher in 94% of the clinical trial arms by an average of 16.7% (p<0.0001). The 2-year survival was higher in 71% of the clinical trial arms by an average of 7.2% (p<0.0001). Conclusions: This study found substantially improved survival among clinical trial participants compared to patients in the SEER database suggesting that survival estimates from clinical trials may not generalize to the “real world.” Potential patient factors such as differences in underlying comorbidity, performance status, disease burden, as well as variation in treatment could not be addressed in this study, though these factors likely explain some of the observed survival differences.

Survival impact on regorafenib (REG) and trifluridine/tipiracil hydrochloride (FTD/TPI) for patients with metastatic colorectal cancer: Single institutional experience.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 43-43
Author(s):  
Keigo Chida ◽  
Daisuke Kotani ◽  
Kentaro Sawada ◽  
Yoshiaki Nakamura ◽  
Akihito Kawazoe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Phase Iii ◽  
First Line ◽  
Standard Chemotherapy ◽  
Exon 2 ◽  
The Real ◽  
Real World Setting ◽  
Tipiracil Hydrochloride

43 Background: Regorafenib (REG) and trifluridine/tipiracil hydrochloride (FTD/TPI) demonstrated overall survival (OS) benefit in patients (pts) with metastatic colorectal cancer (mCRC) in the CORRECT and RECOURSE phase III trials. In Japan, REG and FTD/TPI have been approved in 2013 and 2014, respectively. However, little is known about survival impact on these agents in the real-world setting. Therefore, the aim of this retrospective study was to evaluate the effects of REG and FTD/TPI in pts with mCRC. Methods: We collected medical records from consecutive 1142 pts who had been initiated with first-line chemotherapy for mCRC from 2008 to 2016 at National Cancer Center Hospital East. The survival outcomes were compared between pts from 2008 to 2011 (cohort A) and those from 2012 to 2016 (cohort B). This study excluded pts who have not been refractory or intolerant to standard chemotherapy including fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR antibody if KRAS exon 2/ RAS wild-type tumors. Results: A total of 590 pts were analyzed (cohort A; N = 236 and cohort B; N = 354). More patients received at least one of REG or FTD/TPI in cohort B (16.1% vs. 59.9%, p < 0.001). The time from initiation to end of standard chemotherapy was comparable between the two cohort (20.0 vs. 17.5 months, p = 0.266). With a median follow-up period of 34.9 months, salvage-line OS (sOS) after standard chemotherapy was significantly longer in cohort B (4.8 vs. 6.6 months, p = 0.001), while there was only a favorable trend in cohort B in terms of OS from start of first-line treatment (27.3 vs. 28.5 months, p = 0.516). In cohort B, pts who sequentially received both of REG and FTD/TPI showed longest sOS (median, both of REG and FTD/TPI; 11.3 months, either REG or FTD/TPI; 7.0 months, neither REG nor FTD/TPI; 3.1 months). Conclusions: Our study showed that REG and FTD/TPI led to prolongation of sOS in the real-world setting, indicating the importance of strategies which make all active agents available to pts with mCRC.

Trends in the design and interpretation of metastatic colorectal cancer phase III clinical trials.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 692-692
Author(s):  
Sunil Parimi ◽  
Soundouss Raissouni ◽  
Yongtao Lin ◽  
Jose Gerard Monzon ◽  
Patricia A. Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Trial Design ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
Steady Increase ◽  
Study Results ◽  
Over Time

692 Background: Increasing use of subsequent lines of therapy and crossover in phase III randomized clinical trials (P3 RCTs) has shifted how we perceive the effectiveness of treatments for metastatic colorectal cancer (mCRC). This study aims to characterize the evolution of P3 RCTs in mCRC with respect to clinical trial design and result interpretation. Methods: Abstracts of P3 RCTs of systemic therapy for mCRC conducted between 1980 and 2014 were identified by searching PubMed, Medline, and ASCO abstracts. Data regarding trial design, agent(s) investigated, primary endpoint, secondary endpoint(s), primary endpoint significance and interpretation of the study results (conclusions) were extracted. Results: A total of 422 trials were identified by the search strategy, and 132 eligible trials were included. Over time the sample size of P3 RCTs in mCRC has been increasing and there has been a steady increase in trials studying targeted therapy (see table below for detailed results by decade). A trend towards a smaller percentage of P3 RCTs sponsored by co-operative groups has been observed in recent decades. The most common primary endpoint was overall survival (OS) which was used in 35% of the trials. A decreasing trend in the use of OS was observed since the 1990s. Other common primary endpoints include: progression-free survival (PFS) in 28% and response rate (RR) in 20% of the P3 RCTs. The primary endpoint was met in 45% of the trials. There was discordance between the primary endpoint significance and the authors’ conclusions in 14% of the trials. Conclusions: The design and interpretation of P3 RCTs for mCRC has changed over time from 1980 to present. The use of OS as the primary endpoint is decreasing, while the use of PFS is increasing. [Table: see text]

Effect of subsequent chemotherapy on overall survival in first-line chemotherapy with targeted agents for patients with metastatic colorectal cancer: Systematic review and meta-analysis of randomized control trials.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 782-782
Author(s):  
Daisuke Sakai ◽  
Toshihiro Kudo ◽  
Aya Kato ◽  
Toshinori Sueda ◽  
Hidekazu Takahashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Randomized Clinical Trials ◽  
Progression Free Survival ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
First Line ◽  
Line Chemotherapy

782 Background: One of recent standard first line chemotherapies for metastatic colorectal cancer is doublet of cytotoxic agents, fluorouracil and oxaliplatin or irinotecan, in combination with target agent, bevacizumab, or anti-EGFR antibody as cetuximab or panitumumab for KRAS or RAS wild type (WT). In this decade, nevertheless progression free survival (PFS) of clinical trials was little improved, overall survival (OS) had been increased. Methods: We analyzed data from 14 recently published phase III randomized clinical trials in mCRC to correlate the percentage of patients receiving subsequent chemotherapy with the reported OS. Results: Median PFS and OS were 10.3 and 25.0 months, respectively. In all comer trials, median OS is significantly correlated with the percentage of patients who received subsequent chemotherapy after first line chemotherapy of their disease [regression coefficient (R2) = 0.85 p = 0.0018]. In trials with KRAS WT, a correlation between OS and the rate of subsequent therapy was modest [r2 = 0.605, p = 0.0637]. Median PFS and RR were not correlated with median OS. Conclusions: Our results support the strategy of making salvage chemotherapy available to all patients with advanced CRC to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, PFS might no longer be regarded as the appropriate surrogate end point of OS by which to assess the efficacy of a palliative first-line treatment in CRC.

scholarly journals Are clinical trial results transferable in the real life?

2016 ◽  
Vol 84 (1-2) ◽  
Author(s):  
Enrico Natale ◽  
Alfiera Marsocci
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Recurrent Events ◽  
Randomized Clinical Trials ◽  
Real Life ◽  
Recurrent Event ◽  
The Real ◽  
Number Of Patients ◽  
Clinical Trial Results

<p>Generally in the clinical practice patients are more complex in comparison with those included in the clinical trials. In this article, we discuss three relevant items, which may implement the transferability of the clinical trial results in the real world. The observational studies have fewer restrictions on the number of patients included, due to more relaxed inclusion and exlusion criteria than in randomized clinical trials. The absence of randomization however may lead to potential for bias. The recurrent event analysis may extend the positive results of clinical trials regarding the reductions of the first primary endpoint event to total events, including those beyond the first event. This analysis is of great interest in the clinical practice, where recurrent events are common. Finally the reliability of subgroup analysis is discussed. Pre-specified subgroup analyses are more credible and valuable than <em>post-hoc</em> analyses.</p><p><strong>Riassunto</strong></p><p>Nella pratica clinica i pazienti sono generalmente più complessi rispetto alle popolazioni studiate nei trial clinici. Si rendono necessari pertanto strumenti di analisi che integrino i trial clinici. In questo articolo vengono esaminati alcuni punti di rilevante importanza nella definizione di una corretta applicabilità dei risultati dei trial clinici al mondo reale. Il primo punto riguarda il ruolo e i limiti degli studi osservazionali. Il secondo tratta delle analisi degli eventi ricorrenti, una modalità di analisi dei trial clinici che rende i risultati più aderenti alla vita reale, nella consapevolezza che limitare i dati di outcome al primo evento sia riduttivo rispetto alla necessità di stabilire che l’intervento studiato nel trial confermi la sua efficacia anche sugli eventi successivi al primo. Il terzo punto riguarda la controversa questione delle analisi per sottogruppi, uno strumento utile per generare ipotesi, ma discutibile quando impiegato per rimediare a trial con risultati negativi o estendere i risultati di trial positivi a sottopopolazioni particolari di pazienti. </p>

Pancreatic cancer: Survival in clinical trials versus the real world.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Reith Roy Sarkar ◽  
Rayna Matsuno ◽  
James Don Murphy
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Pancreatic Adenocarcinoma ◽  
Median Survival ◽  
Real World ◽  
Locally Advanced ◽  
The Real ◽  
Survival Differences

216 Background: Physicians often use clinical trial data to estimate expected survival for their patients, however clinical trial results may not generalize to a broader population. Given the need for accurate prognostication, we examined whether the survival of clinical trial pancreatic adenocarcinoma patients was similar to “real world” patients. Methods: We conducted a literature search using Pubmed to identify pancreatic adenocarcinoma Phase III trials published between 2005 and 2012. We excluded secondary or pooled analyses, trials with second-line treatments, and non-randomized studies. We compared clinical trial patients to a cohort of patients from the Surveillance, Epidemiology, and End Results (SEER) program, matching for diagnosis year, age and stage of disease. We evaluated for differences in median survival, 1-year survival, and 2-year survival. Results: We identified 27 trials (3 metastatic, 16 mixed metastatic and locally advanced, 3 locally advanced, and 5 resectable) that fit our search criteria, consisting of 8,438 patients. Compared to SEER the median survival was higher in 98% of the individual clinical trial arms by an average of 3.7 months (p = 0.001). The 1-year overall survival rate was higher in 100% of the clinical trial arms by an average of 12.3% (p <.0001). The 2-year overall survival was higher in 76% of the clinical trial arms by an average of 5.1% (p <.0001). The survival differences between SEER and clinical trials were greatest for patients with metastatic pancreatic cancer. Conclusions: We found that clinical trial patients have profoundly improved survival compared to patients in the SEER database, suggesting that clinical trial survival estimates may not generalize to “real world” patients with pancreatic cancer. Patient performance status, underlying comorbidity, and differences in treatment could not be assessed in SEER, though these factors likely explain a portion of the survival differences. These findings suggest that physicians should use caution when extrapolating survival estimates from clinical trials to the real world.

scholarly journals Systemic therapy for colorectal cancer

2003 ◽  
Vol 11 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Borut Stabuc
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Metastatic Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Randomized Clinical Trials ◽  
Response Rate ◽  
Phase Iii ◽  
Oral Fluoropyrimidines ◽  
Significant Difference

Colorectal cancer alone accounts for around 200,000 deaths in Europe and represents a significant health problem. Although about fifty percent of patients are cured by surgery alone, the other half will eventually die due to metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis. Surgical resection of the primary tumor and regional lymph nodes is the only curative therapy for colorectal cancer. However, adjuvant chemotherapy in stage III for colon cancer following curative resection has been shown to reduce the risk of recurrence by 19-40% and of death by 16-33%. Today, 5-fluoroUracil and Leucovorin given for six months may represent the best adjuvant treatment available The contribution of levamisole to adjuvant treatment seems to be marginal, if any. The benefit of adjuvant chemotherapy for the patients with Dukes B colon cancer is less clear. A meta-analysis of 1,381 patients with advanced colorectal cancer showed a significant increase in response rate with the bolus 5-fluoroUracil and Leucovorin versus 5-fluoroUracil alone but no significant difference in median survival. Continuous infusion allows higher doses of 5-FU than rapid bolus infusion and improves response rate survival and time to progression. Oral fluoropyrimidines (capecitabine and Uracil/Tegafur [UFT]) are as active as intravenous fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines have safety advantages clinical benefits, and are more convenient for patients. Phase III randomized clinical trials in patients with metastatic colorectal cancer demonstrate the significant superiority of combining irinotecan with 5-fluoroUracil and Leucovorin or oxaliplatin with 5-fluoroUracil and Leucovorin over the same 5-fluoroUracil and Leucovorin alone. Several phase II studies have shown that the combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin is very active in metastatic colorectal cancer. Trials with agents acting on novel targets in colorectal cancer are progressing rapidly, including doxifluridine, new inhibitors of thymidylate synthase (ZD9331), oral camptothecins (Rubitecan), multitarget antifolate antimetabolite (Premetrexet), inhibitors of epidermal growth factor receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze inhibitors (Zarnestra). However, a few randomized trials failed to show a survival advantage compared with placebo in patients with advanced refractory colorectal cancer.

scholarly journals Evaluation of Continuous Tumor-Size–Based End Points as Surrogates for Overall Survival in Randomized Clinical Trials in Metastatic Colorectal Cancer

2019 ◽  
Vol 2 (9) ◽  
pp. e1911750
Author(s):  
Tomasz Burzykowski ◽  
Elisabeth Coart ◽  
Everardo D. Saad ◽  
Qian Shi ◽  
Dirkje W. Sommeijer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Tumor Size ◽  
Randomized Clinical Trials ◽  
End Points

The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong

2016 ◽  
Vol 93 (1101) ◽  
pp. 395-400 ◽  
Author(s):  
Ka-On Lam ◽  
Kin-Chung Lee ◽  
Joanne Chiu ◽  
Victor Ho-Fun Lee ◽  
Roland Leung ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hong Kong ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Treatment Pattern ◽  
The Real

The impact of data errors on the outcome of randomized clinical trials

2017 ◽  
Vol 14 (5) ◽  
pp. 499-506 ◽  
Author(s):  
Marc Buyse ◽  
Pierre Squifflet ◽  
Elisabeth Coart ◽  
Emmanuel Quinaux ◽  
Cornelis JA Punt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Randomized Clinical Trials ◽  
Systematic Errors ◽  
Age Related Macular Degeneration ◽  
Random Errors ◽  
Significant Treatment ◽  
Age Related ◽  
The Impact

Background/aims Considerable human and financial resources are typically spent to ensure that data collected for clinical trials are free from errors. We investigated the impact of random and systematic errors on the outcome of randomized clinical trials. Methods We used individual patient data relating to response endpoints of interest in two published randomized clinical trials, one in ophthalmology and one in oncology. These randomized clinical trials enrolled 1186 patients with age-related macular degeneration and 736 patients with metastatic colorectal cancer. The ophthalmology trial tested the benefit of pegaptanib for the treatment of age-related macular degeneration and identified a statistically significant treatment benefit, whereas the oncology trial assessed the benefit of adding cetuximab to a regimen of capecitabine, oxaliplatin, and bevacizumab for the treatment of metastatic colorectal cancer and failed to identify a statistically significant treatment difference. We simulated trial results by adding errors that were independent of the treatment group (random errors) and errors that favored one of the treatment groups (systematic errors). We added such errors to the data for the response endpoint of interest for increasing proportions of randomly selected patients. Results Random errors added to up to 50% of the cases produced only slightly inflated variance in the estimated treatment effect of both trials, with no qualitative change in the p-value. In contrast, systematic errors produced bias even for very small proportions of patients with added errors. Conclusion A substantial amount of random errors is required before appreciable effects on the outcome of randomized clinical trials are noted. In contrast, even a small amount of systematic errors can severely bias the estimated treatment effects. Therefore, resources devoted to randomized clinical trials should be spent primarily on minimizing sources of systematic errors which can bias the analyses, rather than on random errors which result only in a small loss in power.

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