Henry Letocha

Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

BackgroundIntegument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial.MethodsIntegument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity.Results154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity.ConclusionsFirst-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity.Trial registrationClinicalTrials.gov NCT00508404

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer

Background:To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC).Methods:154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression.Results:Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease. Median response duration was longer in RAS WT (13.0 months) vs RAS MT (5.8 months) (hazard ratio (HR): 0.16). Median progression-free survival was longer in RAS WT vs MT (11.2 vs 7.3 months; HR, 0.37) and was also longer in RAS WT/BRAF WT vs RAS or BRAF MT (13.2 vs 6.9 months; HR, 0.25). Incidence of adverse events was similar regardless of RAS/BRAF status, and no new safety signals were noted. Among patients with RAS WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression.Conclusions:First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with RAS WT and RAS WT/BRAF WT vs MT mCRC tumours and was well tolerated.

Amphiregulin (AREG) expression and response to first-line panitumumab (pmab) plus FOLFIRI in metastatic colorectal cancer (mCRC).

731 Background: Biomarker analyses have shown that patients (pts) with RAS wild-type (WT) mCRC can achieve overall survival (OS) benefits with first-line pmab plus chemotherapy. Other biomarkers may exist that could optimize pt selection. Epidermal growth factor receptor ligand (eg AREG) levels have been correlated with OS during anti-EGFR therapy. Here we investigate the relationship between AREG expression and treatment outcome in a single-arm first-line mCRC study of pmab + FOLFIRI. Methods: Qualified reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure AREG RNA expression in archival formalin-fixed, paraffin embedded tumor samples from mCRC pts in two pmab trials (STEPP and 314). The STEPP analysis was used to establish a cut-off point in AREG expression that identified the best responders. This cut-off was applied prospectively to samples previously analyzed for KRAS in the 314 trial. Using the KRASMT subgroup as a non-responding comparator, Cox proportio...