Komal Gupte-Singh

Quality-adjusted survival of nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma: a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis

PurposeTo compare the quality-adjusted survival of nivolumab plus ipilimumab combination and nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma based on a minimum 36-month follow-up from the CheckMate 067 trial.MethodsOverall survival was partitioned into time without symptoms of progression or toxicity (TWiST), time with treatment-related gradeu2009≥u20093 adverse events after randomization but before progression (TOX), and time from progression until end of follow-up or death (REL). Mean quality-adjusted TWiST (Q-TWiST) was calculated by multiplying the mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Sensitivity analyses included varying utilities of TOX and REL; Q-TWiST gains at different follow-up times were calculated using EQ-5D-3L utilities from the trial. Relative Q-TWiST gain of ≥u200910% was considered clinically important.ResultsCompared with ipilimumab-treated patients, those who received nivolumabu2009+u2009ipilimumab combination had significantly longer TWiST and TOX but shorter REL; nivolumab-treated patients had significantly longer TWiST, shorter REL, and shorter but statistically nonsignificant TOX. Mean Q-TWiST was highest for nivolumabu2009+u2009ipilimumab (23.5xa0months; 95% CI 21.9–25.2), followed by nivolumab (21.8xa0months; 95% CI 20.2–23.4) and ipilimumab (15.3xa0months; 95% CI 13.9–16.6). Relative Q-TWiST gains were favorable and clinically important for nivolumabu2009+u2009ipilimumab combination (+u200936.81%) and nivolumab alone (+u200929.18%) versus ipilimumab alone. Relative gains increased with follow-up from 3 to 40xa0months for all comparisons. These gains remained consistent in magnitude and direction in the different sensitivity analyses.ConclusionsNivolumabu2009+u2009ipilimumab combination and nivolumab alone resulted in a statistically significant and clinically important improvement in quality-adjusted survival compared with ipilimumab alone.

Confirming the timing of phase-based costing in oncology studies: a case example in advanced melanoma

Abstract Aims: The utilization of healthcare services and costs among patients with cancer is often estimated by the phase of care: initial, interim, or terminal. Although their durations are often set arbitrarily, we sought to establish data-driven phases of care using joinpoint regression in an advanced melanoma population as a case example. Methods: A retrospective claims database study was conducted to assess the costs of advanced melanoma from distant metastasis diagnosis to death during January 2010–September 2014. Joinpoint regression analysis was applied to identify the best-fitting points, where statistically significant changes in the trend of average monthly costs occurred. To identify the initial phase, average monthly costs were modeled from metastasis diagnosis to death; and were modeled backward from death to metastasis diagnosis for the terminal phase. Points of monthly cost trend inflection denoted ending and starting points. The months between represented the interim phase. Results: A total of 1,671 patients with advanced melanoma who died met the eligibility criteria. Initial phase was identified as the 5-month period starting with diagnosis of metastasis, after which there was a sharp, significant decline in monthly cost trend (monthly percent change [MPC]u2009=u2009–13.0%; 95% CIu2009=u2009–16.9% to –8.8%). Terminal phase was defined as the 5-month period before death (MPCu2009=u2009–14.0%; 95% CIu2009=u2009–17.6% to –10.2%). Limitations: The claims-based algorithm may under-estimate patients due to misclassifications, and may over-estimate terminal phase costs because hospital and emergency visits were used as a death proxy. Also, recently approved therapies were not included, which may under-estimate advanced melanoma costs. Conclusions: In this advanced melanoma population, optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastasis and before death, respectively. Joinpoint regression can be used to provide data-supported phase of cancer care durations, but should be combined with clinical judgement.

Sequential treatment approaches in the management of BRAF wild-type advanced melanoma: a cost–effectiveness analysis

AIMnTo evaluate the cost-effectiveness of treatment sequences with checkpoint inhibitors in patients with BRAF wild-type melanoma.nnnMATERIALS & METHODSnUsing a discrete event simulation model, cost and health outcomes were estimated. Pooled data from CheckMate 067/069 trials were used to calculate survival outcomes including treatment-free interval extrapolated over a patients lifetime. Costs accounted for treatment, administration, toxicity, and disease management.nnnRESULTSnFirst-line anti-PD-1xa0+ anti-CTLA-4 initiating sequences had the highest estimated mean survival gain (7.6-7.7 years), driven by a longer estimated mean treatment-free interval (5.3 years). Incremental costs per incremental quality-adjusted life year gained for anti-PD-1 + anti-CTLA-4 followed by chemotherapy were US

1223PDQuality-adjusted survival of combined nivolumab plus ipilimumab (NIVO+IPI) or NIVO alone vs IPI among treatment-naïve patients (pts) with advanced melanoma (MEL): a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis

30,955 versus anti-PD-1 initiating sequences, within the willingness-to-pay threshold.nnnCONCLUSIONnAnti-PD-1xa0+ anti-CTLA-4 initiating sequences for BRAF wild-type melanoma are cost-effective versus anti-PD-1.