Exploratory analyses assessing the impact of early tumour shrinkage and depth of response on survival outcomes in patients with RAS wild-type metastatic colorectal cancer receiving treatment in three randomised panitumumab trials
Purpose To report exploratory analyses of early tumour shrinkage (ETS) and depth of response (DpR) in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), receiving the first-line treatment in three randomised panitumumab trials. Methods Data from the PRIME (NCT00364013), PEAK (NCT0...
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Published in: | Journal of cancer research and clinical oncology Vol. 144; no. 2; pp. 321 - 335 |
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Main Authors: | , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Berlin/Heidelberg
Springer Berlin Heidelberg
01-02-2018
Springer Nature B.V |
Subjects: | |
Online Access: | Get full text |
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Summary: | Purpose
To report exploratory analyses of early tumour shrinkage (ETS) and depth of response (DpR) in patients with
RAS
wild-type (WT) metastatic colorectal cancer (mCRC), receiving the first-line treatment in three randomised panitumumab trials.
Methods
Data from the PRIME (NCT00364013), PEAK (NCT00819780) and PLANET (NCT00885885) studies were included. Median DpR, the proportion of patients achieving ETS ≥ 20% or ≥ 30% at week 8, and the impact of ETS and DpR (including by category) on outcome were analysed. Factors associated with ETS and DpR and the optimal ETS/DpR cut-off values for predicting improved overall survival (OS) were assessed.
Results
Overall, 505, 170 and 53 patients had
RAS
WT mCRC in PRIME, PEAK and PLANET, respectively. Patients receiving panitumumab had higher ETS rates (≥ 30%: PRIME 59% vs. 38%; PEAK 64% vs. 45%) and greater DpR (PRIME: 54% vs. 46%; PEAK: 65% vs. 46%) than those receiving treatment without panitumumab. In multiple regression analyses, panitumumab treatment, liver-only metastases and WT
BRAF
status were consistently associated with improved ETS and DpR outcomes. Irrespective of treatment, ETS and DpR were associated with improved progression-free survival, overall survival and resection rates; most resections occurred in patients in the two highest DpR categories. In PRIME and PEAK, respectively, the optimal cut-offs for predicting improved OS were 32 and 34% for ETS, and 59 and 70% for DpR.
Conclusions
These exploratory analyses suggest that panitumumab is associated ETS and DpR benefits in patients with
RAS
WT mCRC and that achieving these endpoints during first-line treatment is linked with favourable outcomes. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-News-3 content type line 23 |
ISSN: | 0171-5216 1432-1335 |
DOI: | 10.1007/s00432-017-2534-z |