Quality‐adjusted time without symptoms or toxicity analysis of pazopanib versus sunitinib in patients with renal cell carcinoma

Abstract

BACKGROUND In a phase 3, randomized, open-label trial (COMPARZ; NCT00720941), pazopanib was found to be non-inferior to sunitinib in terms of progression-free survival in patients with metastatic renal cell carcinoma with no prior therapy. Overall treatment differences were evaluated in a post hoc analysis using a quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) methodology. METHODS Each patient’s overall survival was partitioned into 3 mutually exclusive health states: grade 3 or 4 toxicity (TOX), time without symptoms of disease or grade 3/4 toxicity (TWiST), and time after progression or relapse (REL). Time spent in each state was weighted by a health-state utility associated with that state and summed to calculate the Q-TWiST. A threshold utility analysis was used, applying utilities across the range of 0 (similar to death) to 1 (perfect health). RESULTS A total of 1,110 patients were enrolled (557 pazopanib, 553 sunitinib). The mean time spent with TOX was 31 days (95% confidence interval, 13–49) higher for sunitinib compared with pazopanib. In the threshold utility analysis, the difference in Q-TWiST ranged from -11 days (utility TOX=1, REL=0) to 43 days (TOX=0, REL=1), in favor of pazopanib across most utility combinations. Differences were significant in less than half of the utility combinations examined, typically when the utility for TOX was lower than the utility for REL. CONCLUSIONS Patients randomized to pazopanib had slightly longer Q-TWiST compared with sunitinib patients, primarily due to a reduced length of time spent with grade 3/4 toxicities.

Pazopanib as first-line therapy for patients with metastatic kidney cancer

“…Среди больных, получавших пазопаниб, чаще отмечалось повышение уровней аланинамино-трансферазы (60 против 43% в группе сунитиниба), в то время как у пациентов на фоне сунитиниба чаще отме-чались усталость (63 против 55%), ладонно-подошвен-ный синдром (50 против 29%) и тромбоцитопения (78 против 41%) по сравнению с пациентами, получавшими пазопаниб. В группе пазопаниба прекратили исследова-ние из-за нежелательных эффектов 24% пациентов (Motzer et al, 2013) [14][15][16].…”

“…Согласно опубликованному анализу COMPARZ, у боль-ных, принимавших пазопаниб, токсические реакции раз-вивались несколько позднее (Q-TWiST) по сравнению с реципиентами сунитиниба [16].…”

Oncology Gold StandardTM practical consensus recommendations 2016 for treatment of advanced clear cell renal cell carcinoma

“…The risk of discontinuation and interruptions due to clinically significant toxicity will form an important consideration [Figure 2]. [4142]…”

Q‐TWiST: What really matters to the cancer patient?

“…Berry et al performed threshold analyses to project the entire range of Q‐TWiST outcomes for different combinations of utilities of TOX and REL. However, it is important to identify the relevant utilities directly from the patient to provide meaningful interpretations of the threshold analyses . For example, “perfect health” may not be the same as “the best health expected for this disease” to a cancer patient .…”

“…Currently, there is also little information on what constitutes a clinically important difference in Q‐TWiST scores . Guidelines would be helpful in settings where little survival difference is anticipated and the primary concerns lie with balancing disease symptoms and treatment toxicities . This will ultimately make the Q‐TWiST model more suitable as a clinical tool that can be directly applied in patient care rather than just a mathematical model …”