Association Of Skin Toxicity (St) Severity With Clinical Outcomes And Health-Related Quality Of Life (Hrqol) With Panitunumab (Pmab)

4038 Background: STs are associated with epidermal growth factor receptor (EGFr) inhibition. Studies of anti-EGFr inhibitors have shown associations between the severity of ST per clinical toxicity grading and response rate, progression-free-survival (PFS) and overall survival (OS). However a correlation between these endpoints and ST severity as measured by ST patient reported outcomes (PRO) and the impact of ST on HRQoL is unknown. We evaluated the associations among PFS, OS and ST PRO, and the impact of ST on overall HRQoL for Pmab. Methods: In a phase 3 study of mCRC patients (pts) with disease progression after treatment (tx) with standard chemotherapy, pts were randomized to best supportive care (BSC) ± Pmab 6mg/kg Q2W. ST was measured using modified NCI-CTC v3.0 grading criteria and a modified Dermatology Life Quality Index (mDLQI). HRQoL (EQ-5D and EORTC QLQ-C30 Global QoL subscale) and CRC symptoms (NCCN/FACT CRC symptom index, FCSI) were also measured. Analyses of ST with PFS and OS were restricted to pts in the Pmab arm with ≥ grade (gr) 1 ST that were progression-free at least 28 days. These analyses were adjusted for randomization factors. Hazard ratios (HR) and correlation analyses were used to determine relationships between PFS and OS to ST, and ST to overall HRQoL. Results: Tx with Pmab (n=231) prolonged PFS vs BSC alone (n=232; p<.0001). The incidence of gr 2–4 ST was higher in the Pmab arm. OS was significantly prolonged in pts with more severe ST (gr 2–4 vs. gr 1; HR=0.67; p=0.0235). Lower mDLQI scores (worse ST) also predicted improved OS (Cox model, p<0.0001). Similar results were seen with PFS. Pearson correlation coefficients showed that the minimum post- baseline mDLQI score was inversely associated with post-baseline median HRQoL and CRC symptom scores, suggesting that Pmab pts with more severe ST have a higher (better) HRQoL (p=0.0006, 0.0148, 0.2487) and improved CRC symptom scores (p=0.0649). Conclusions: Pts with gr 2–4 ST appear to experience longer PFS and OS compared to those with gr 1 ST. Pts reporting the greatest bother from their ST also tend to report better overall HRQoL and reduced CRC symptoms. [Table: see text]