Q-TWiST analysis comparing ipilimumab/dacarbazine vs placebo/dacarbazine for patients with stage III/IV melanoma

Abstract

Background:Study CA184024 was a multinational, randomised, double-blind, phase 3 study comparing ipilimumab/dacarbazine (DTIC) vs placebo/DTIC in patients with untreated stage III/IV melanoma, which showed that ipilimumab significantly improves survival in patients with metastatic melanoma. The objective of this analysis was to compare the quality-adjusted survival experience among patients in this trial.Methods:Survival time was partitioned into health states: toxicity, time before progression without toxicity, and relapse until death or end of follow-up. Q-TWiST (quality-adjusted time without symptoms of disease or toxicity of treatment) was calculated as the utility-weighted sum of the mean health state durations. Analyses were repeated over extended follow-up periods.Results:Based on a combination of trial-based and external utility scores, the Q-TWiST difference in this trial was 0.50 months (P=0.0326) favoring ipilimumab after 1 year. The Q-TWiST difference was 1.5 months with 2 years of follow-up (P=0.0091), 2.36 months at 3 years (P=0.005) and 3.28 months at 4 years (P=0.0074).Conclusion:During the first year of study, there was little difference between groups in quality-adjusted survival. However, after 2, 3 and 4 years follow-up for patients with extended survival, the benefits of IPI+DTIC vs PLA+DTIC for advanced melanoma continue to accrue.

Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone in Patients with Malignant Melanoma: A Meta-Analysis

“…Then, 92 full-text articles were assessed for eligibility. Eight possible candidates were retrieved for detailed examination by reading the full text [18] – [25] . The screening process is summarized in a flow diagram ( Fig.…”

Trial Watch

“…In addition, (1) Sherrill and colleagues evaluated the quality-adjusted survival of patients enrolled in study CA184024, a multinational, randomized, double-blind, Phase III trial testing dacarbazine (an alkylating agent currently approved by the US FDA for the treatment of Hodgkin’s lymphoma and melanoma) alone vs. dacarbazine plus ipilimumab in subjects with previously untreated metastatic melanoma; 59 , 76 (2) Santegoets and collaborators performed an exploratory T-cell monitoring study in the context of Phase I/II dose escalation/expansion trial testing ipilimumab plus a GM-CSF-secreting allogeneic vaccine in prostate carcinoma patients; 77 and (3) Kwek and co-authors monitored the humoral immune responses elicited by the co-administration of ipilimumab and a fixed dose of GM-CSF 102 , 103 in subjects with prostate cancer 81 . In these clinical settings, ipilimumab-based immune(chemo)therapy was well tolerated and associated with promising clinical responses, 79 , 80 , 82 with a single exception 78 .…”

Targeting immune checkpoints in unresectable metastatic cutaneous melanoma: a systematic review and meta‐analysis of anti‐CTLA‐4 and anti‐PD‐1 agents trials

“…Of these, two retrospective studies [17,18], 18 single arm or randomized studies without control treatment [11,13,14,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], one study with sequential treatment with a BRAF inhibitor [34], and one study with resectable melanoma [35] were excluded from the meta-analysis. Seven duplicate or ad hoc studies [36][37][38][39][40][41][42] were also excluded. Following verification of eligibility, a total of six phase II or III randomized controlled trials (three with anti-CTLA-4 [7,43,44] and three with anti-PD-1 [12,45,46] monoclonal antibodies) were selected for the meta-analysis.…”