PD-024 Retrospective analysis of quality of life and early tumour shrinkage during first-line FOLFOX4 ± panitumumab in RAS wild-type metastatic colorectal carcinoma

Abstract

Introduction: Metastatic colorectal cancer (mCRC) is rarely curable. Prolonging survival and maintaining or improving quality of life (QoL) are therefore key treatment goals. Achieving tumour shrinkage is also an important goal in these patients, as it can reduce tumour burden and increase the chance of surgical resection. In particular, early tumour shrinkage (ETS) may rapidly relieve tumour-related symptoms and provide an early indication of sensitivity to treatment.We therefore conducted an exploratory retrospective analysis on the impact of FOLFOX4 chemotherapy, with or without panitumumab, on patient-reported QoL in patients with RAS wild type (WT) mCRC, categorised by ETS status. Methods: A randomised phase 3 open-label study of first-line panitumumab + FOLFOX4 vs FOLFOX4 (NCT00364013) enrolled adults with untreated mCRC and an Eastern Cooperative Oncology Group performance status of 0-2. This analysis includes patients with RAS WT tumours (n = 505). QoL ( pre-specified endpoint) was assessed using the EuroQoL 5-domain health state index (HSI) and overall health rating (OHR) ≤7 days before randomisation and every 4 weeks until disease progression, with a final assessment at safety follow-up. In an exploratory analysis of QoL, patients were categorised according to the presence or absence of ETS, defined as a reduction in tumour size by ≥30% by week 8, and by the presence or absence of tumour-related symptoms at baseline (defined as EQ-5D pain/discomfort scale score >1). Differences in QoL were assessed using analysis of covariance and a mixed-effect linear model. Minimally important differences (MIDs) were prospectively defined as 0.08 for HSI and 7 for OHR. Results: Of 1183 patients enrolled in PRIME, 505 had RAS WT mCRC, of whom 456 were included in the QoL analysis (panitumumab + FOLFOX4, n = 232; FOLFOX4, n = 224). Overall rates of compliance with the QoL assessments (evaluable vs expected assessments) were 57% for both HSI and OHR. There were no statistically significant differences in overall QoL (least squares mean treatment difference [95% confidence interval]) between treatment arms from baseline to treatment discontinuation (HSI: - 0.011 [-0.042, 0.020]; OHR: -1.640 [-4.257, 0.976]). More patients receiving panitumumab + FOLFOX4 vs FOLFOX4 had ETS (59% vs. 38%; p < 0.001). In patients with tumour symptoms at baseline, there were statistically significantly greater improvements in QoL in those with ETS vs those without ETS (Table; p = 0.02 for both HSI and OHR). In addition, in patients with symptomatic disease and ETS, the magnitude of improvement from baseline in HSI score (+0.096) was greater than the MID. In the overall population (i.e. irrespective of symptomatic disease at baseline), there was no difference in change in QoL for those with ETS vs those without ETS. Conclusion: Addition of panitumumab to FOLFOX4 in first-line therapy of RAS WT mCRC increased ETS rates, with no negative effect on overall QoL - in terms of OHR and HSI - compared with FOLFOX4 alone in this retrospective analysis. Furthermore, our exploratory analysis suggests that, for those patients with tumour symptoms at baseline, achieving ETS may be associated with improvement in QoL.