Abstract
PurposeTo 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.MethodsData 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.ResultsOverall, 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.ConclusionsThese 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.
Highlights
Tumour response, as defined by Response Evaluation Criteria In Solid Tumours (RECIST), is a common endpoint in clinical trials, and requires that tumour shrinkage of ≥ 30% is confirmed at consecutive visits (Therasse et al 2000; Eisenhauer et al 2009)
We further build on these data by reporting new exploratory analyses of the optimal early tumour shrinkage (ETS) and depth of response (DpR) cut-offs to predict improved overall survival (OS), multiple regression analyses of factors associated with ETS and DpR, the impact of DpR by category on outcome in PEAK, and the impact of ETS and DpR on response and resection outcomes
Multiple regression analyses were performed to determine baseline factors associated with ETS in the PRIME and PEAK studies
Summary
As defined by Response Evaluation Criteria In Solid Tumours (RECIST), is a common endpoint in clinical trials, and requires that tumour shrinkage of ≥ 30% is confirmed at consecutive visits (Therasse et al 2000; Eisenhauer et al 2009). Tumour shrinkage (ETS of ≥ 20% or ≥ 30% assessed after 6 or 8 weeks of treatment) can provide an early indication of sensitivity to treatment (Piessevaux et al 2013; Giessen et al 2013; Modest et al 2013; Douillard et al 2015; Heinemann et al 2015; Cremolini et al 2015), whereas depth of response (DpR) assesses the maximum tumour shrinkage achieved by a patient during treatment (Heinemann et al 2015). Exploratory analyses of first-line trial data demonstrated that both ETS and DpR were associated with improved overall survival (OS) (Mansmann et al 2013; Cremolini et al 2015; Douillard et al 2015; Heinemann et al 2015; Stintzing et al 2016; Rivera et al 2017). We further build on these data by reporting new exploratory analyses of the optimal ETS and DpR cut-offs to predict improved OS, multiple regression analyses of factors associated with ETS and DpR, the impact of DpR by category on outcome in PEAK, and the impact of ETS and DpR on response and resection outcomes (where available)
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