Health-related quality of life and colorectal cancer-specific symptoms in patients with chemotherapy-refractory metastatic disease treated with panitumumab

Abstract

Purpose: Panitumumab monotherapy is approved for chemotherapy-refractory wild-type KRAS metastatic colorectal cancer (mCRC). Patient-reported outcomes-although important in the palliative setting-have not been reported in this patient population.

Methods: In a phase 3 trial (n = 463), patients with chemotherapy-refractory mCRC were randomized 1:1 to panitumumab plus best supportive care (BSC) or BSC alone. Patient-reported outcomes were assessed using the NCCN/FACT CRC Symptom Index (FCSI) and EQ-5D Index. KRAS tumor status was analyzed in a prospectively defined, retrospective analysis. Average difference in change from baseline between treatment groups was evaluated using linear mixed and pattern-mixture models.

Results: KRAS tumor status and post-baseline patient-reported outcomes were available for 363 patients. Linear mixed models indicated significant differences in the FCSI score (difference in least-squares [LS] adjusted means [95% CI]; 5.62 [2.38, 8.86]) and the EQ-5D Index (difference in LS adjusted means [95% CI]; 0.22 [0.12, 0.32]) favoring panitumumab over BSC in patients with wild-type KRAS mCRC. By pattern-mixture analysis, the advantage of panitumumab over BSC was more pronounced in those patients with wild-type KRAS mCRC who did not drop out of the study early. In patients with mutant KRAS mCRC, no differences were observed between groups.

Conclusions: Panitumumab-treated patients with wild-type KRAS mCRC maintained better control of CRC symptoms and quality of life compared with BSC alone, extending our understanding of the benefits of panitumumab treatment beyond improvements in progression-free survival.

Fig. 1

a Least-squares mean differences in the change from baseline in the FCSI scores between panitumumab plus BSC and BSC alone for patients with wild-type KRAS mCRC by analysis week, linear mixed models. Note: This model includes data only through week 13. Inclusion of week 17 data, which are missing for more than 80% of the analysis population, caused model instability to the extent that treatment effects could not be estimated. b Least-squares mean differences in the change from baseline in the EQ-5D Index between panitumumab plus BSC and BSC alone for patients with wild-type KRAS mCRC by analysis week (KRAS PRO analysis set), linear mixed models. FSCI Functional Assessment of Cancer Therapy, Colorectal Symptom Index; BSC best supportive care; mCRC metastatic colorectal cancer; EQ-5D EuroQol 5-Dimensions Index

Fig. 2

Unadjusted average change from baseline in FCSI score by week of assessment and dropout pattern (KRAS PRO analysis set). FSCI Functional Assessment of Cancer Therapy, Colorectal Symptom Index

Fig. 3

a Least-squares mean differences in the change from baseline in the FCSI scores between panitumumab plus BSC and BSC alone for patients with wild-type KRAS mCRC in the late dropout group by analysis week, pattern-mixture model. b Least-squares mean differences in the change from baseline in the EQ-5D Index score between panitumumab plus BSC and BSC alone for patients with wild-type KRAS mCRC in the late dropout group by analysis week, pattern-mixture model. FSCI Functional Assessment of Cancer Therapy, Colorectal Symptom Index, BSC best supportive care, mCRC metastatic colorectal cancer, EQ-5D EuroQol 5-Dimensions Index