Matching-adjusted Indirect Treatment Comparison Research Articles

Cost effectiveness of axicabtagene ciloleucel versus tisagenlecleucel for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in the United States

Aims To assess from a US payer perspective the cost-effectiveness of the chimeric antigen receptor T (CAR T)-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) to treat relapsed or refractory (r/r) large B-cell lymphoma (LBCL) following ≥2 systemic therapy lines. Methods A three-state (i.e. pre-progression, post-progression, and death) partitioned survival model was used to estimate the quality-adjusted life-years (QALYs) and costs for patients on each treatment over a lifetime horizon. Progression-free survival (PFS) and overall survival (OS) were based on a matching-adjusted indirect treatment comparison (MAIC) that accounted for differences in trial population baseline characteristics. Mixture cure models (MCMs) were used to account for long-term survivors. Costs included drug acquisition and administration for the CAR T-cell therapies and conditioning chemotherapy, apheresis, CAR T-specific monitoring, transplant, hospitalization, adverse events, routine care, and terminal care. Health state utilities were derived from trial and published data. Sensitivity analyses included probabilistic sensitivity analyses (PSAs) and an analysis of extremes that assessed the results across a vast array of combinations of parametric OS and PFS curves across the two therapies. Results Compared to tisa-cel, axi-cel resulted in 2.31 QALYs gained and a cost reduction of $1,407 in the base case. In the PSA, the cost per QALY gained was ≤$31,500 in 95% of the 1,000 simulations. In the analysis of extremes, the cost per QALY gained was ≤$7,500 in 99% of the 1,296 combinations of MCMs and ≤$40,000 in 95% of the 1,296 combinations of standard models. Limitations In absence of head-to-head comparative data, we relied on a MAIC, which cannot account for all possible confounders. Moreover, some outcomes (i.e. transplantations, hospitalizations, adverse events (AEs)) were not adjusted in the MAIC. Conclusions In this simulation, axi-cel was a superior treatment option as it is predicted to achieve better outcomes at lower or minimal incremental costs versus tisa-cel.

Carfilzomib 56mg/m2 Twice-Weekly in Combination with Dexamethasone and Daratumumab (KdD) Versus Daratumumab in Combination with 8 Cycles of Bortezomib and Dexamethasone (DVd); A Matching-Adjusted Indirect Treatment Comparison

Carfilzomib 56mg/m2 Twice-Weekly in Combination with Dexamethasone and Daratumumab (KdD) Versus Daratumumab in Combination with 8 Cycles of Bortezomib and Dexamethasone (DVd); A Matching-Adjusted Indirect Treatment Comparison

Matching-adjusted indirect treatment comparison of siponimod and other disease modifying treatments in secondary progressive multiple sclerosis

Background: Siponimod, interferon beta-1a (IFNβ-1a), IFNβ-1b and natalizumab have been evaluated as treatments for secondary progressive multiple sclerosis (SPMS) in separate randomized controlled trials (RCTs), but not head-to-head. These trials included heterogeneous patient populations, which limits the use of standard network meta-analysis (NMA) for indirect treatment comparison (ITC) of relative efficacy. Matching-adjusted indirect comparison (MAIC) aims to correct these cross-trial differences. We compared siponimod to other disease modifying treatments (DMTs) in SPMS using MAIC.Methods: Individual patient data (IPD) were available for siponimod (EXPAND), while only published summary data were available for IFNβ-1a (Nordic Study, SPECTRIMS, IMPACT), IFNβ-1b (North American Study, European Study) and natalizumab (ASCEND). MAICs were conducted between siponimod and the other DMTs by re-weighting patients in EXPAND based on logistic regression.Results: Siponimod was determined to be statistically significantly more effective for the outcome of time to 6 month confirmed disability progression (CDP) compared with 22 µg IFNβ-1a and 250 µg IFNβ-1b, and for the outcome of time to CDP-3 compared with 60 µg IFNβ-1a. Siponimod was numerically but not statistically superior for CDP in all other comparisons. For annualized relapse rate (ARR), with the exception of natalizumab, siponimod was numerically but not statistically superior to all comparators.Conclusions: EXPAND provides evidence of the efficacy of siponimod compared with placebo, and these MAICs complement this by demonstrating improved efficacy of siponimod relative to DMTs. Siponimod offers a significant therapeutic advance that may slow disease progression compared to other DMTs in an EXPAND-like population with secondary progressive disease.

A matching-adjusted indirect treatment comparison (MAIC) of daratumumab–bortezomib–melphalan–prednisone (D-VMP) versus lenalidomide–dexamethasone continuous (Rd continuous), lenalidomide–dexamethasone 18 months (Rd 18), and melphalan–prednisone–thalidomide (MPT)

D-VMP is a novel treatment for transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM). D-VMP significantly prolonged PFS versus VMP in the ALCYONE trial. The FIRST trial investigated Rd given in 28-day cycles until disease progression, Rd for 18 cycles, and MPT for 12 cycles for TIE NDMM. As no randomized controlled trials comparing D-VMP to standard-of-care regimens such as those in FIRST are available, an MAIC was performed to assess relative OS and PFS for D-VMP from ALYCONE and Rd continuous, Rd 18, and MPT from FIRST. Individual patient data for D-VMP in ALCYONE were weighted to match aggregated baseline patient characteristics for each arm of FIRST. D-VMP significantly improved OS versus MPT and Rd 18, with a trend favoring D-VMP versus Rd continuous. D-VMP performed significantly better than all FIRST comparators for PFS. This MAIC demonstrates OS and PFS benefits for D-VMP versus Rd continuous, Rd 18, and MPT.

Estimating the comparative efficacy of cladribine tablets versus alternative disease modifying treatments in active relapsing–remitting multiple sclerosis: adjusting for patient characteristics using meta-regression and matching-adjusted indirect treatment comparison approaches

Objectives: To estimate the comparative efficacy of cladribine tablets versus alternative disease modifying therapies (DMTs) – fingolimod, natalizumab, alemtuzumab and ocrelizumab – in adults with active relapsing–remitting multiple sclerosis (RRMS), using meta-regression to provide subpopulation-specific estimates of drug effect. Additionally, to determine the feasibility of conducting a matching-adjusted indirect comparison (MAIC) to validate the meta-regression results.Methods: A published systematic literature review (SLR) identified studies evaluating the efficacy of cladribine tablets and alternative DMTs in the management of active RRMS. A series of meta-regression models were run with adjustment for baseline risk, fitted to data from the intention-to-treat cohorts of trials identified in the SLR. A non-parametric MAIC analysis adjusted for differences between studies by reweighting patient-level data from the index trial to match the mean baseline characteristics reported for trials with only aggregate data.Results: The meta-regression analysis showed significant overlap in credible intervals for the hazard ratios of 6 month confirmed disability progression (CDP-6M) and annualized relapse rate (ARR), with no therapy statistically dominating in terms of efficacy and all therapies estimated to reduce the ARR compared to placebo in all subpopulations. In the MAIC analysis, cladribine tablets showed a reduction in CDP-6M and ARR comparable to alemtuzumab before and after matching.Conclusion: This analysis has demonstrated that cladribine tablets have comparable relative efficacy to other highly efficacious DMTs in active RRMS across all subpopulations, thus validating the comparative effectiveness results from previous network meta-analysis. The MAIC analysis showed that cladribine tablets are comparable in efficacy to alemtuzumab in the treatment of patients with RRMS.

An Indirect Comparison between Bosutinib, Nilotinib and Dasatinib in First-Line Chronic Phase Chronic Myeloid Leukemia

IntroductionSeveral randomized controlled trials (RCTs) compare second generation tyrosine kinase inhibitors (TKIs) with imatinib (IM) for the first-line (1L) treatment of chronic phase chronic myeloid leukemia (CP-CML). However, an examination indicated cross-trial heterogeneity in terms of disease and patient characteristics (baseline risk score, age, trial region, and post-baseline IM dose escalation) and outcomes reported (type and time of evaluation). For this reason, a matching adjusted indirect treatment comparison (MAIC) can be used to assess comparative efficacy. The objective of this study was to compare the efficacy of bosutinib (BOS) with nilotinib (NIL) and dasatinib (DAS) in 1L CP-CML via unanchored MAICs.MethodsAs well as heterogeneity in baseline characteristics, differences in the amount of IM dose escalations in earlier clinical pivotal trials (ENESTnd: 15.9% at 12 months; DASISION 20% at 24 months) relative to more recent ones (BFORE: 27.5% and 30.9% at 12 and 24 months, respectively) were observed. Because differences in IM dose-escalation regimens are trial design matters, they cannot be adjusted for using anchored MAICs. Therefore, an unanchored MAIC (which dismisses the common comparator arm, in this case IM) was used.Unanchored MAICs comparing BOS with NIL and DAS were performed to match the summary statistics in the BFORE trial to the reported summary statistics in the ENESTnd (NIL) and the DASISION (DAS) trials. Outcomes assessed included major molecular response (MMR) at 12 months and at any time after 12 months, complete cytogenetic response (CCyR) by 12 months, and deep molecular response (MR4) at 12 months. Statistical significance was assessed based on confidence intervals (CI; significant when CI excludes 1). The sample size of the matching-adjusted BOS population was estimated using the effective sample size (ESS). No adjustments for multiple comparisons were made.ResultsThe MAICs showed an MMR at 12 months of 49.32% (vs 47.13% before the MAIC, N=244, ESS=186) for BOS vs 44% for NIL (OR 1.24, 95% CI [0.87-1.77], N=282) and an MMR at any time of 58.09% (vs 57.79% before MAIC, N=244, ESS=142) for BOS vs 57% for NIL (OR 1.05, 95% CI [0.72-1.5], N=282), and 58.52% (vs 58.16% before MAIC, N=239, ESS=192) for BOS vs 52% for DAS (OR 1.3, 95% CI [0.9-1.88], N=259). BOS had a CCyR by 12 months of 82.59% (vs 82.38% before MAIC, N=244) vs 80% for NIL (OR 1.19, 95% CI [0.75-1.87], N=282, ESS=195) and 80.47% (vs 82.01% before MAIC, N=239, ESS=185) vs 83% for DAS (OR 0.84, 95% CI [0.53-1.35], N=259). MR4 at 12 months was 20.34% (vs 20.49% before MAIC, N=244, ESS=185) for BOS vs 12% for NIL (OR 1.87, 95% CI [1.15-3.05], N=282). MMR and MR4 at month 12 were not reported for DAS.DiscussionThe general MAIC limitations (impact of having access to only marginal covariate distribution, choice of scale for indirect comparisons, choice of target population and sampling variation in the target population) apply to our analyses as well. Nevertheless, indirect comparisons using unanchored MAICs were conducted because cross-trial heterogeneity in patient baseline characteristics could bias the results of a naïve comparison and increases in IM dose escalation over time could bias the results of an anchored MAIC. The unanchored MAICs indicated that BOS was numerically higher than NIL for all response rates examined, however, except for MR4, none were statistically significant. BOS had a numerically higher MMR at any time and a numerically lower CCyR by 12 months compared with DAS, however, neither were statistically significant. BOS therefore seems to be an equally effective TKI as NIL and DAS in the 1L CP-CML setting. These findings, based on statistical methods, should be confirmed by clinical research. DisclosuresMuresan:Ingress-health Nederland BV: Employment. Mamolo:Pfizer: Employment, Equity Ownership. Cappelleri:Pfizer: Employment, Equity Ownership. Crescenzo:Pfizer: Employment. Leip:Pfizer: Employment, Equity Ownership. Viqueira:Pfizer: Employment, Equity Ownership. Heeg:Ingress-health Nederland BV: Employment, Equity Ownership, Research Funding.

Matching-adjusted indirect treatment comparison of guselkumab and ixekizumab in patients with moderate-to-severe psoriasis

Matching-adjusted indirect treatment comparison of guselkumab and ixekizumab in patients with moderate-to-severe psoriasis

PSY52 - Vost Effectiveness of Blinatumomab Vs Inotuzomab Ozogamicin (INOTUZUMAB) in Adult Patients with Relapsed or Refracory (R/R) Acute Lymphoblastic Leukemia (ALL) with Zero or One Prior Salvage Therapy (S0/S1) from a US Payer Perspective

To estimate the incremental cost-effectiveness ratio (ICER=cost per QALY gained) of blinatumomab vs. inotuzumab in adults with R/R S0/S1 ALL based on matching-adjusted indirect treatment comparison (MAIC) of TOWER and INO-VATE-ALL trials. Cost-effectiveness was estimated using a partitioned-survival model with outcomes based on published summary data from INO-VATE and patient-level data from TOWER adjusted to match patient characteristics in INO-VATE using MAIC. Three separate analyses were conducted: (1) inotuzumab overall survival (OS) obtained by applying the anchored MAIC-adjusted hazard ratio (HR) for inotuzumab vs. blinatumomab (1.40, 95%CI 0.87-2.24) to blinatumomab MAIC-adjusted TOWER OS (Gompertz distribution); (2) inotuzumab and standard-of-care (SOC) OS based on Weibull mixture cure distribution fit to INO-VATE-ALL OS; blinatumomab OS obtained by applying MAIC-adjusted HR for blinatumomab vs. SOC (0.55, 95%CI 0.38-0.80) to INO-VATE-ALL SOC OS; and (3) unanchored comparison of MAIC-adjusted Weibull mixture cure fit to blinatumomab OS from TOWER and inotuzumab OS from INO-VATE-ALL. The same event-free survival (EFS) was assumed for complete responders due to inconsistent definitions of EFS between the two studies while complete remission rates were MAIC adjusted. Costs were based on published sources and included blinatumomab/inotuzumab treatment (medications and administration), important adverse events (costs of cytokine release syndrome assumed to be captured in inpatient administration), stem-cell transplant, salvage treatments, and terminal care. Utilities were based on EORTC-8D values derived from EORTC QLQ-C30 assessments in TOWER. A 50-year horizon, US payer perspective, and 3% discount rate for costs and QALYs were employed. In all 3 analyses, blinatumomab was more efficacious (incremental QALYs: 0.59~1.89) and slightly more costly (incremental costs: $27,021~$29,021), yielding an ICER=$14,341, $49,131 and $24,952 per QALY gained for analyses 1~3, respectively. For various approaches of applying the MAIC results, blinatumomab was cost-effective vs. inotuzumab in R/R ALL adults with S0/S1 from the US payer perspective.

Matching-adjusted indirect treatment comparison of ribociclib and palbociclib in HR+, HER2- advanced breast cancer.

BackgroundRibociclib (RIBO) and palbociclib (PALBO), combined with letrozole (LET), have been evaluated as treatments for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in separate Phase III randomized controlled trials (RCTs), but not head-to-head. Population differences can lead to biased results by classical indirect treatment comparison (ITC). Matching-adjusted indirect comparison (MAIC) aims to correct these differences. We compared RIBO and PALBO in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer using MAIC.MethodsPatient-level data were available for RIBO (MONALEESA-2), while only published summary data were available for PALBO (PALOMA-2). Weights were assigned to MONALEESA-2 patient data such that mean baseline characteristics matched those reported for PALOMA-2; the resulting matched cohort was used in comparisons. Limited by the results reported in PALOMA-2, progression-free survival (PFS) was the primary comparison. Cox regression models were used to calculate adjusted hazard ratios (HRs) for PFS, before indirect treatment comparison (ITC) was performed with 95% confidence intervals. An exploratory analysis was performed similarly for overall survival using earlier PALBO data (PALOMA-1). Grade 3/4 adverse events were also compared.ResultsRacial characteristics, prior chemotherapy setting, and the extent of metastasis were the most imbalanced baseline characteristics. The unadjusted PFS HRs were 0.556 (0.429, 0.721) for RIBO+LET versus LET alone and 0.580 (0.460, 0.720) for PALBO+LET versus LET alone. MAIC adjustment resulted in an HR of 0.524 (0.406, 0.676) for RIBO+LET versus LET. PFS ITC using unadjusted trial data produced an HR of 0.959 (0.681, 1.350) for RIBO versus PALBO, or 0.904 (0.644, 1.268) with MAIC. Unadjusted overall survival HR of RIBO versus PALBO was 0.918 (0.492, 1.710); while exploratory MAIC was 0.839 (0.440, 1.598). ITC of grade 3/4 adverse events yielded a risk ratio of 0.806 (0.604, 1.076).ConclusionMAIC was performed for RIBO and PALBO in the absence of a head-to-head trial: though not statistically significant, the results favored RIBO.

254P - Matching-adjusted indirect treatment comparison of ribociclib and palbociclib as first-line treatments for HR+, HER2– ABC

Background: Ribociclib (RIB) and palbociclib (PAL) combinations with letrozole (LET) vs LET alone have been evaluated in separate Phase 3 randomized controlled trials in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC); however, no head-to-head comparative studies have been conducted. Classic indirect treatment comparison (ITC) can lead to biased results due to differences in patient populations and trial designs. These differences can be corrected by using the matching-adjusted indirect comparisons (MAIC) technique. Here, we compare RIB and PAL in patients with HR+, HER2– ABC using MAIC. Methods: Individual patient data were available for the RIB trial (MONALEESA-2). As only published summary data were available for the PAL trial (PALOMA-2), RIB data were adjusted to closely match the PAL data. Data for RIB-treated patients were assigned weights so that weighted mean baseline characteristics matched those reported for PAL. Overall survival data have not been reported for PALOMA-2, thus only progression-free survival (PFS) data were compared. Adjusted hazard ratios (HRs) for PFS were calculated using weighted Cox regression models and used to calculate indirect HRs with 95% confidence intervals (CIs). Classic frequentist ITC was performed before and after adjustment. ITC of Grade 3/4 adverse events (AEs) was also performed. Results: The unadjusted PFS HR (95% CI) for RIB+LET vs LET was 0.556 (0.429; 0.721) and for PAL+LET vs LET was 0.580 (0.460; 0.720). MAIC adjustment for age, race, region, Eastern Cooperative Oncology Group status, disease stage at diagnoses, sites of metastases, and chemotherapy setting at baseline provided a RIB+LET vs LET HR estimate of 0.501 (0.365; 0.688). The HR for unadjusted ITC of RIB vs PAL was 0.959 (0.681; 1.350) and by MAIC was 0.864 (0.586; 1.274). ITC of Grade 3/4 AEs yielded a risk ratio (RR) of 0.81 (0.61; 1.08) for RIB vs PAL. Conclusions: Using MAIC methodology due to a lack of head-to-head trials, the resulting HRs for PFS were comparable. Similarly, using ITC, AE profiles were also comparable although the RR for AEs slightly favored RIB. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation Funding: Novartis Pharmaceuticals Corporation Disclosure: A. Forsythe: Consultant for Novartis. D. Chandiwana, M. Monaco: Novartis employee and stocks/shares. All other authors have declared no conflicts of interest.

Matching-Adjusted Indirect Treatment Comparison of Bosutinib, Dasatinib, Nilotinib and Ponatinib on Survival for Second Line Chronic Phase Chronic Myeloid Leukemia Patients

Background: In clinical trials of second line and later line therapies for chronic myeloid leukemia (CML), to date only single arm trials have been conducted for the available treatments (i.e. Bosutinib, Dasatinib, Nilotinib and Ponatinib). These trials included heterogeneous patient populations in terms of line of treatment, stage of disease and other patient- and disease baseline characteristics that may impact the outcomes of the treatment. This hampers any direct or indirect comparisons of these second line CML treatments in terms of efficacy measures such as progression-free survival (PFS) and overall survival (OS). In this situation (i.e. lack of common comparator), matching-adjusted indirect treatment comparisons (MAICs) can be applied.Objective: The aim of this research was to compare the efficacy (PFS and OS) of Bosutinib, Dasatinib, Nilotinib and Ponatinib in second line chronic phase CML patients by means of MAICs. Patient data are reweighted such that their medians on demographic and clinical characteristics match those of the aggregated comparator trial, in order to adjust for cross-trial differences in those baseline characteristics. Outcomes of the reweighted patient level dataset are then compared with those of the aggregated comparator trial.Methods: A systematic literature review of second-line or later CML Phase II and Phase III clinical trials identified 2 trials for Bosutinib, 11 trials for Dasatinib, 8 trials for Nilotinib and 2 trials for Ponatinib. For the MAIC, only second line chronic phase trials with three or more years of follow-up (to allow for sufficient differentiation of treatments over time) were considered, resulting in 1 trial for Bosutinib (NCT00261846), 1 trial for Dasatinib (CA180-034), 1 trial for Nilotinib (NCT00109707) and no trials for Ponatinib. To adjust for cross-trial differences, patient data from the Bosutinib trial were subject to the inclusion and exclusion criteria reported in the comparator trials, and were weighted to match all available summary baseline characteristics reported in the 1 Dasatinib trial and the 1 Nilotinib trial. The baseline characteristics considered for reweighing were as follows: age, gender, Imatinib resistant/intolerant, disease duration, and prior stem cell transplantation. After the MAICs, PFS and OS were compared based on hazard ratios (HR) derived by Cox proportional hazard (PH) regressions using the reweighed Bosutinib dataset. The Cox PH assumption was tested with log cumulative hazard plots, Schoenfeld residuals and its corresponding statistical test. In case the PH assumption did not hold, Cox regressions with time varying coefficients were tested and the relative restricted mean survival time (RMST) was estimated.Results: Comparing Bosutinib to Nilotinib resulted in HRs for PFS and OS of 2.0 (<0.01) and 1.4 (p=0.109) respectively. When compared to Dasatinib, Bosutinib showed a non-significant HR of 1.3 (p=0.30) in favor of Bosutinib for OS and a significant 1.6 HR (p<0.01) for PFS. In the PFS and OS analyses compared to Dasatinib, the PH assumption was violated based on the statistical test or almost violated according to the visual plots. Therefore, we examined the relative restricted mean survival times, which were 1.123 (p=0.02) for PFS and 1.025 (p=0.41) for OS.Discussion: After performing MAICs to adjust for cross-trial differences in baseline characteristics, Bosutinib appeared to have a significantly greater PFS than Nilotinib (p<0.01). Based on the relative RMST analyses, Bosutinib also appeared to have a significantly greater PFS than Dasatinib, at the p<0.05 level. For OS the findings were numerically positive in favor of Bosutinib, but not statistically significant, compared to both. However, qualitatively, Bosutinib appears to be an equally effective second line chronic phase CML therapy. The greater PFS compared to Nilotinib and Dasatinib, especially at the end of the follow up period for Bosutinib, may translate into future OS benefits not yet observed.A limitation of our study is that we could only correct for observed differences between the trials, and not for unobserved ones. Also, the reweighing was performed for all relevant reported baseline characteristics; not all baseline characteristics were reported in all trials. Both limitations could have an impact on the outcomes and therefore the study conclusions. DisclosuresMuresan:Ingress-health Nederland BV: Employment. Mamolo:Pfizer Inc: Employment, Equity Ownership. Cappelleri:Pfizer Inc: Employment, Equity Ownership. Shapiro:Pfizer Inc: Employment, Equity Ownership. Crescenzo:Pfizer Inc: Employment. Su:Pfizer: Employment, Equity Ownership; Bristol Myers Squibb: Equity Ownership. Heeg:Ingress-health Nederland BV: Employment, Equity Ownership, Research Funding.

Matching-adjusted indirect treatment comparison in patients with radioiodine-refractory differentiated thyroid cancer

Matching-adjusted indirect treatment comparison in patients with radioiodine-refractory differentiated thyroid cancer Gabriel Tremblay,1 Tim Holbrook,2 Gary Milligan,2 Corey L Pelletier,1 Petra Rietschel1 1Eisai Inc, Woodcliff Lake, NJ, USA; 2Adelphi Real World, Manchester, UKAims: Lenvatinib and sorafenib have been evaluated in separate Phase III placebo-controlled trials in patients with radioiodine-refractory differentiated thyroid cancer; however, no head-to-head comparative studies are available. We performed an indirect comparison of these agents using matching-adjusted indirect comparison (MAIC) to adjust for differences in baseline characteristics, a technique allowing comparison of two studies with patient-level data available for one but only aggregate data available for the other.Patients and methods: Individual patient data were available for the SELECT trial (lenvatinib versus placebo) whereas only published summary data were available for the DECISION trial (sorafenib versus placebo); therefore the SELECT data were adjusted to closely match the DECISION data. Data for patients in SELECT were assigned weights so that weighted mean baseline characteristics of the SELECT population matched those reported for DECISION. Adjusted hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS; corrected for crossover using rank-preserving structural failure time models) were calculated using weighted Cox regression models. Adjusted HRs were used to calculate indirect HRs with 95% confidence intervals (CIs).Results: Indirect treatment comparison using unadjusted clinical trial data resulted in an HR for PFS of 0.36 (95% CI 0.22&ndash;0.57) for lenvatinib versus sorafenib; MAIC resulted in an HR of 0.33 (95% CI 0.20&ndash;0.53), suggesting a statistically significantly superior PFS for lenvatinib. The HR for crossover-corrected OS for lenvatinib versus sorafenib was 0.77 (95% CI 0.44&ndash;1.35); MAIC resulted in an OS HR of 0.73 (95% CI 0.40&ndash;1.35).Conclusion: After adjusting for differences in baseline characteristics using MAIC, lenvatinib was associated with statistically significantly superior PFS compared with sorafenib in patients with radioiodine-refractory differentiated thyroid cancer. This suggests lenvatinib may provide superior efficacy compared with sorafenib for patients with radioiodine-refractory differentiated thyroid cancer. Keywords: indirect comparison, lenvatinib, overall survival, progression-free survival, radioiodine-refractory, sorafenib