Abstract
Background
Gemcitabine-based combinations in advanced pancreatic cancer have been reported to
have superior activity compared with gemcitabine alone. The results of the commonly
used endpoints of clinical trials after chemotherapy or targeted therapy have been
poorly reported.
Methods and Materials
We performed a search of randomized trials of systemic treatment that included gemcitabine
plus chemotherapy or targeted therapy versus gemcitabine alone. For selected trials,
the differences between the treatment arms for every endpoint were calculated, and
a correlation analysis between these differences and the differences in overall survival
was performed for every intermediate endpoint. Whenever a correlation coefficient
was significant, regression analysis was performed. Finally, an analysis was performed
to evaluate the factors that could mediate and moderate the effect of progression-free
survival on overall survival.
Results
In addition to overall survival, progression-free survival, the overall response rate,
and the disease control rate were the most frequently reported endpoints. Of the possible
surrogate endpoints of overall survival, progression-free survival appears to be a
reliable endpoint to assess chemotherapy (R2 = 0.646) and chemotherapy plus targeted therapy (R2 = 0.530) regimens and the disease control rate to assess chemotherapy (R2 = 0.569). Of the factors that could limit the effect of progression-free survival
on overall survival, the interval of radiologic evaluation could play a role.
Conclusion
In the selected trials, progression-free survival and the disease control rate were
the most reliable surrogate endpoints of overall survival. Similar to the time-to-event
endpoints, a standardization of response-related endpoints is strongly recommended.
Keywords
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Article info
Publication history
Published online: November 28, 2015
Accepted:
November 23,
2015
Received in revised form:
November 3,
2015
Received:
August 17,
2015
Identification
Copyright
© 2015 Elsevier Inc. All rights reserved.
