Disease-Free Survival Versus Overall Survival As a Primary End Point for Adjuvant Colon Cancer Studies: Individual Patient Data From 20,898 Patients on 18 Randomized Trials

Sargent, Daniel J.; Wieand, Harry S.; Haller, Daniel G.; Gray, Richard; Benedetti, Jacqueline; Buyse, Marc; Labianca, Roberto; Seitz, Jean François; O’Callaghan, Christopher J.; Francini, Guido; Grothey, Axel; O’Connell, Michael J.; Catalano, Paul J.; Blanke, Charles D.; Kerr, David; Green, Erin; Wolmark, Norman; Thewis, André; Goldberg, Richard M.; Gramont, Aimery de

doi:10.1200/jco.2005.01.6071

Cited by 600 publications

(407 citation statements)

References 34 publications

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“…The survival rates for Stage I, Stage II, and Stage III were 74%, 54%, and 49%, respectively, according to the data from Surveillance, Epidemiology and End Results [14]. Due to the lack of long-term follow-up, and since RFS correlates with OS in colon cancer patients who received adjuvant chemotherapy [15], we decided to measure RFS as a primary outcome. Consistent with data from other studies, our study confirmed that patients with Stage III colon cancer have statistically significant inferior RFS rates compared to Stage I and II disease.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with short recurrence-free survival in completely resected colon cancer

Alnimer

Ghamrawi

Aburahma

et al. 2017

Journal of Community Hospital Internal Medicine Perspectives

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Background: Several factors could affect disease recurrence in surgically resected colon cancer. While the role of certain factors such as cancer stage and grade is well established, the role of other factors (e.g., histological subtypes) is yet to be determined. Objective:Therefore, we conducted a study to evaluate the impact of several factors in recurrence-free survival (RFS) in patients who were disease free following surgical resection of the colon cancer. Design/Methods: Data were collected for patients with Stage I–III colon cancer who underwent complete surgical resection of the tumor between January 2010 and December 2015 in our institution. A total of 90 subjects met the inclusion criteria and were included in the study. The following factors were collected at the time of surgical resection of the colonic tumor: patient’s age, gender, colon cancer stage, grade and histological subtype, body mass index, hemoglobin A1c, and smoking history. Results: A total of 28 patients (31%) developed recurrence and had a mean follow-up time of 19.8 months (range: 2–54.4 months). Median RFS was 54.4 months with a 5-year RFS of 49%. Advanced colonic cancer stage and mucinous histological subtype were associated with shorter RFS with an HR of 2.37, 95% CI = 1.38–4.06, and 95% CI = 1.02–5.90, respectively. Current smokers or those who quit less than 15 years earlier tended to have worse RFS with an HR of 2.47, 95% CI = 0.98–6.27. Conclusion: Advanced colon cancer stage and mucinous histological subtype are independent risk factors for cancer recurrence and shorter RFS in completely resected colonic tumor.

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Section: Discussionmentioning

confidence: 99%

Factors associated with short recurrence-free survival in completely resected colon cancer

Alnimer

Ghamrawi

Aburahma

et al. 2017

Journal of Community Hospital Internal Medicine Perspectives

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“…In breast and other tumour types, the highest predictive power was achieved when meta-analyses were performed using individual patient data on a small group of trials (Sargent et al, 2005;Buyse et al, 2007). Hackshaw et al (2005) noted an association between treatment effects on progression and survival when comparing anthracycline-based regimens in advanced breast cancer and suggested use of time-to-progression as a surrogate marker for survival.…”

Section: Discussionmentioning

confidence: 99%

“…Several meta-analyses have been published (Table 1) that show a link between time-toprogression (TTP) or progression-free survival (PFS) with overall survival (OS) in metastatic colorectal or non-small cell lung cancer (Johnson et al, 2006) and colon cancer in the adjuvant setting (Sargent et al, 2005). For breast cancer, a moderately strong correlation between 2-year disease-free survival and 5-year overall survival was observed in the adjuvant setting (Ng et al, 2008).…”

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confidence: 99%

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

Sherrill

Amonkar

et al. 2008

Br J Cancer

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The relationship between overall survival (OS) and disease progression end points has been demonstrated in colorectal, colon, and non-small cell lung cancers. We assessed the association between OS and time-to-progression (TTP) or progression-free survival (PFS) in metastatic breast cancer (MBC) studies. A literature search retrieved all randomised controlled trials since 1994 in patients with MBC in which OS and either TTP or PFS were reported. Summary data on trial and patient characteristics were abstracted. Study effect sizes were derived as the ratio of median progression (or survival) times, which approximates the hazard ratio. Effects were centred at zero for regression analyses weighted by sample size. Numerous treatments were represented in 67 studies (17 081 patients). Modeling showed a positive association between outcomes for progression and survival (R 2 ¼ 0.30) with a slope of 0.32 (Po0.001) and a non-significant intercept. Thus, a treatment effect on TTP/PFS translated into a concordant effect on OS, but with attenuated effect size. Similar results were found in models of subsets and sensitivity analyses. These results demonstrate that treatment effects on progression end points in MBC trials are expected to result in treatment differences on OS that are smaller yet consistently in the same direction. British Journal of Cancer (2008) Most studies of anticancer agents are designed and powered to show differences between groups on disease progression end points such as response rates, time-to-progression, time-torecurrence or disease-free survival. Although increased survival time is clearly an implicit goal, it is difficult to establish in randomised studies when standard clinical practise is to change treatments at the onset of new progressive events. Especially in the metastatic setting, where expected survival time may be very short, the use of drug combinations or sequential use of multiple drug classes is commonplace. Increasingly, patients in clinical trials are offered alternate treatment upon progression. Consequently, few studies actually demonstrate an unequivocal survival benefit using intent-to-treat analysis approaches.In several tumour types, efforts have been made to justify the use of alternate, more easily established end points by showing how well they are correlated with survival. Several meta-analyses have been published (Table 1) that show a link between time-toprogression (TTP) or progression-free survival (PFS) with overall survival (OS) in metastatic colorectal or non-small cell lung cancer (Johnson et al, 2006) and colon cancer in the adjuvant setting (Sargent et al, 2005). For breast cancer, a moderately strong correlation between 2-year disease-free survival and 5-year overall survival was observed in the adjuvant setting (Ng et al, 2008). A meta-analysis of metastatic breast cancer studies found a positive relationship between objective response and overall survival on an individual patient basis, but the relationship was less clear when treatment regimens were compared...

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“…The ACCENT group has assembled individual patient data from large randomized phase III clinical trials in adjuvant colon cancer conducted worldwide. Their work led to the acceptance of disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) for fluorouracil-based regimens in adjuvant colon cancer studies by United States Food and Drug Administration (FDA) (Sargent et al, 2005(Sargent et al, , 2007.…”

Section: Introductionmentioning

confidence: 99%

“…In Sargent et al (2005)'s work, surrogacy of DFS was evaluated not only based on Copular R 2 trial , but also by the simple measures based on regression or correlation type of analysis.…”

Section: Introductionmentioning

confidence: 99%

Comparative assessment of trial-level surrogacy measures for candidate time-to-event surrogate endpoints in clinical trials

Renfro

Bot

Burzykowski

et al. 2011

Computational Statistics & Data Analysis

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Summary: Various meta-analytical approaches have been applied to evaluate putative surrogate endpoints (S) of primary clinical endpoints (T), however a systematic assessment of their performance is lacking. Existing methods in the meta-analytic framework can be grouped into two types -conventional and model-based trial-level surrogacy (TLS) measures. Conventional TLS assess the association between treatment effects on S and T, including correlation coefficients and Rsquare measures from weighted linear regression. Model-based TLS included Copula R 2 proposed by Burzykowski et al. (2001) which measures the ability to predict treatment effect on T based on observed treatment effect on putative S. We examined and compared the estimation performance of these frequently used surrogacy measures in a large scale simulation study. The impact of several key factors on the estimation performance was assessed, including the strength of the true surrogacy, the amount of effective information provided by available data, and the range of within trial treatment effect on S and T. The TLS can be estimated accurately and precisely by both types of surrogacy measures when the true surrogacy is strong, number of trials is large, and the range of within trial treatment effects is wide. When one or more factors deviate from the "best" scenarios, both types of TLS measures tend to underestimate the true surrogacy with increased variability. The estimation performance of conventional measures is similar to model-based measures, but with higher computational efficiency. The findings are applied to a large individual patient data pooled analysis in colon cancer.

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Disease-Free Survival Versus Overall Survival As a Primary End Point for Adjuvant Colon Cancer Studies: Individual Patient Data From 20,898 Patients on 18 Randomized Trials

Cited by 600 publications

References 34 publications

Factors associated with short recurrence-free survival in completely resected colon cancer

Factors associated with short recurrence-free survival in completely resected colon cancer

Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer

Comparative assessment of trial-level surrogacy measures for candidate time-to-event surrogate endpoints in clinical trials

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