OBJECTIVES: Panitumumab, a fully human anti-EGFr monoclonal antibody, is approved in Europe as monotherapy for mCRC patients with wild-type (non-mutated) KRAS tumors. In a randomized phase 3 trial, chemorefractory mCRC patients receiving panitumumab plus BSC had significantly longer progression-free survival vs. BSC alone. Analyses of the KRAS gene showed that all responders had wild type KRAS. This analysis evaluates patient-reported outcomes (PROs) by KRAS status.
METHODS: In the phase 3 trial, mCRC patients with disease progression after standard chemotherapy were randomized 1:1 to panitumumab (6mg/kg Q2W) plus BSC vs. BSC alone. KRAS status was assessed in 427/463 (92%) patients. Analyses of PROs included HRQOL (EQ-5D) and CRC symptoms (NCCN/FACT CRC Symptom Index, FCSI). Linear mixed models estimating change from baseline in PRO scores were employed. Sensitivity analysis using pattern-mixture models evaluated the appropriateness of the assumption that PRO data were missing at random. Pattern-mixture models can provide unbiased estimates of treatment effects, taking into account missing data patterns. ANCOVA of the time-adjusted AUC using last value carried forward (LVCF) and slope imputation methods were also used.
RESULTS: There were 363/427 (85%) patients in the KRAS-PRO analysis set (188 panitumumab [112 wild-type KRAS; 76 mutant KRAS]; 175 BSC [96 wild-type KRAS; 79 mutant KRAS]). Linear mixed models showed significant differences in CRC symptoms and HRQOL in favor of panitumumab in patients with wild-type KRAS. No differences were observed in patients with mutant KRAS. Pattern-mixture analysis showed that significant differences in CRC symptoms (FCSI scores: difference in LS adjusted means [95%CI]; 5.746 [1.448, 10.044] and HRQOL (EQ-5D scores: difference in LS adjusted means [95%CI]; 0.319 [0.184, 0.454]) in favor of panitumumab treated patients with wild-type KRAS were particular to patients who progressed greater or equal to 9 weeks.
CONCLUSIONS: Panitumumab patients with wild-type KRAS showed significantly better HRQOL and CRC symptoms compared to BSC alone.
