Characteristics and response outcomes of long-term survivors in studies of first-line panitumumab for metastatic colorectal cancer

Abstract

Introduction: First-line trials have shown that the EGFR-targeted monoclonal antibody Pmab can improve survival in patients (pts) with RAS wild-type (WT) mCRC. Baseline disease characteristics and response outcomes are described for a subset of pts with very extended overall survival (OS). Methods: Analyses (retrospective) included pts with RAS WT mCRC (i.e. tumours containing no mutations in KRAS or NRAS exons 2 [codons 12/13], 3 [codons 59/61] and 4 [codons 117/146]) from the phase 3 PRIME study (NCT00364013; Pmab+FOLFOX4 vs FOLFOX4) and phase 2 PEAK study (NCT00819780; mFOLFOX6+Pmab or bevacizumab). Baseline disease characteristics and response outcomes (early tumour shrinkage [ETS]; depth of response [DpR]) were summarised for longand short-term survivors. Definitions: ETS - reduction of ≥30% in the sum of the longest diameters of measurable target lesions at 8 weeks; DpR - max. % change from baseline to nadir in pts who had tumour shrinkage, or % change at progression in pts with no shrinkage (if there was no progression, DpR could not be defined); long-term survivors - the 25% of pts with the longest OS. In a second pooled analysis, long-term survival was defined as ≥45 months. Results: For 664 pts analysed, median survival was 39.5 months (PRIME: 120/475 pts) and 45.9 months (PEAK: 34/137 pts) using the 25% cut-off. Long-term survivors were more likely than short-term survivors to be randomised to Pmab (PRIME: 61% vs 46%; PEAK: 62% vs 47%), have an Eastern Cooperative Oncology Group performance status of 0 (PRIME: 74% vs 50%; PEAK: 76% vs 56%), have BRAF WT, left-sided primary tumours, to have received study treatment for ≥9 months, have undergone resection, and to have experienced ETS (Table); median DpR was also higher. Overall, 124/664 pts (19%) survived ≥45 months; baseline characteristics and response outcomes were similar to those in the 25% analysis (data not shown). (Table presented) Conclusions: Long-term survivors were more likely to have received Pmab, have baseline characteristics associated with favourable prognosis, and have better response outcomes (ETS, resection, DpR). They may reflect a cohort of pts with tumour biology that has greater sensitivity to Pmab.