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Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points.

Lee L, Wang L, Crump M - Ann. Oncol. (2011)

Bottom Line: For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73-0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS.For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35-0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS.Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Canada.

ABSTRACT

Background: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS).

Methods: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (r(s)).

Results: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73-0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35-0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS.

Conclusions: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data.

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Related in: MedlinePlus

Correlation between differences in 3-year event or progression-free survival and 5-year overall survival in aggressive non-Hodgkin's lymphoma. Solid line represents the linear regression with 95% confidence intervals indicated by the dashed line.
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fig3: Correlation between differences in 3-year event or progression-free survival and 5-year overall survival in aggressive non-Hodgkin's lymphoma. Solid line represents the linear regression with 95% confidence intervals indicated by the dashed line.

Mentions: For strongly correlated end points, linear regression was carried out through the origin. In aggressive NHL, the regression of differences in CR and 3-year EFS yielded a slope of 0.9 ± 0.1 [±1 standard error (SE) of the estimate] with a R2 of 0.78 (Figure 2). The regression of differences in 3-year EFS/PFS and 5-year OS yielded a slope of 0.7 ± 0.1 (±1 SE of the estimate) with a R2 of 0.66 for aggressive histology NHL (Figure 3). In indolent NHL, the regression of differences in CR and 3-year EFS yielded a slope of 0.9 with a large SE (0.3) due to the smaller number of trials.


Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points.

Lee L, Wang L, Crump M - Ann. Oncol. (2011)

Correlation between differences in 3-year event or progression-free survival and 5-year overall survival in aggressive non-Hodgkin's lymphoma. Solid line represents the linear regression with 95% confidence intervals indicated by the dashed line.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101365&req=5

fig3: Correlation between differences in 3-year event or progression-free survival and 5-year overall survival in aggressive non-Hodgkin's lymphoma. Solid line represents the linear regression with 95% confidence intervals indicated by the dashed line.
Mentions: For strongly correlated end points, linear regression was carried out through the origin. In aggressive NHL, the regression of differences in CR and 3-year EFS yielded a slope of 0.9 ± 0.1 [±1 standard error (SE) of the estimate] with a R2 of 0.78 (Figure 2). The regression of differences in 3-year EFS/PFS and 5-year OS yielded a slope of 0.7 ± 0.1 (±1 SE of the estimate) with a R2 of 0.66 for aggressive histology NHL (Figure 3). In indolent NHL, the regression of differences in CR and 3-year EFS yielded a slope of 0.9 with a large SE (0.3) due to the smaller number of trials.

Bottom Line: For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73-0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS.For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35-0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS.Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Canada.

ABSTRACT

Background: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS).

Methods: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (r(s)).

Results: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73-0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35-0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS.

Conclusions: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data.

Show MeSH
Related in: MedlinePlus