A Q-TWiST analysis comparing panitumumab plus best supportive care (BSC) with BSC alone in patients with wild-type KRAS metastatic colorectal cancer

Abstract

Background:Panitumumab+best supportive care (BSC) significantly improved progression-free survival (PFS) vs BSC alone in patients with chemo-refractory wild-type KRAS metastatic colorectal cancer (mCRC). We applied the quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis to provide an integrated measure of clinical benefit, with the objective of comparing quality-adjusted survival between the two arms. As the trial design allowed patients on BSC alone to receive panitumumab after disease progression, which confounded overall survival (OS), the focus of this analysis was on PFS.Methods:For each treatment group, the time spent in the toxicity (grade 3 or 4 adverse events; TOX), time without symptoms of disease or toxicity (TWiST), and relapse (after disease progression; REL) states were estimated by the product-limit method, and adjusted using utility weights derived from patient-reported EuroQoL 5-dimensions measures. Sensitivity analyses were performed in which utility weights (varying from 0 to 1) were applied to time in the TOX and REL health states.Results:There was a significant difference between groups favouring panitumumab+BSC in quality-adjusted PFS (12.3 weeks vs 5.8 weeks, respectively, P<0.0001) and quality-adjusted OS (P=0.0303).Conclusion:In patients with chemo-refractory wild-type KRAS mCRC, panitumumab+BSC significantly improved quality-adjusted survival compared with BSC alone.

Systematic review of health state utility values for economic evaluation of colorectal cancer

“…Some studies did not report their settings or were multinational or multicentre studies [55–60]. Studies were mostly published in the last 15–20 years and focussed narrowly on different interventions at specific stages of CRC.…”

Clinical Pharmacokinetics and Pharmacodynamics of the Epidermal Growth Factor Receptor Inhibitor Panitumumab in the Treatment of Colorectal Cancer

“…Furthermore, longer OS and PFS were correlated with a high grade of skin toxicity (grade 2–4) in patients treated with panitumumab [53]. By combining the efficacy and safety measures in a Q-twist analysis, the quality-adjusted PFS was significantly longer in the panitumumab arm (12.3 weeks) versus the BSC-alone arm (5.8 weeks) [54]. In the open-label extension study focusing on safety, 176 of the patients who had progressive disease in the BSC arm received panitumumab monotherapy [55].…”

Quality‐adjusted time without symptoms or toxicity (Q‐TWiST): patient‐reported outcome or mathematical model? A systematic review in cancer

“…Most studies utilized a health index, whereas other studies had a battery of health questionnaires. The EQ‐5D and the subjective health estimation were used to calculate utilities in two studies (18.2%) each . Three (27.3%) studies used utility weights from non‐study participants with similar cancers .…”