Mobocertinib and amivantamab are used to treat EGFR ex20ins + non-small-cell lung cancer (NSCLC) but have not been compared in a head-to-head trial. We conducted a matching-adjusted indirect comparison to compare their efficacy. Efficacy outcomes were generally comparable for mobocertinib and amivantamab. These findings confirm the efficacy of different treatment options for patients with EGFR ex20ins + NSCLC. Introduction: Exon 20 insertions (ex20ins) mutations of the EGFR gene account for 1% to 2% of all non-small-cell lung cancers (NSCLCs). Targeted therapies have been developed to treat this cancer type but have not been studied in head-to-head trials. Our objective was to use a matching-adjusted indirect comparison (MAIC) to assess the efficacy of mobocertinib and amivantamab in patients with NSCLC EGFR ex20ins mutations who were previously treated with platinum-based chemotherapy. Materials and Methods: An unanchored MAIC was conducted to estimate the treatment effects of mobocertinib and amivantamab using individual-level data from the mobocertinib phase I/II single-arm trial (NCT02716116) and published data from the amivantamab single-arm CHRYSALIS trial (NCT02609776). Confirmed overall response rate (cORR), progression-free survival (PFS), overall survival (OS), and duration of response (DoR) were assessed. Results: Both trials were comparable in terms of study population, study design, and outcome definitions and included 114 patients who received mobocertinib and 114 patients who received amivantamab. After MAIC weighting, all reported baseline characteristics were balanced bet ween mobocer tinib and amivantamab. The weighted odds ratio (OR) [95% confidence interval (CI)] comparing mobocertinib to amivantamab was 0.56 (0.30-1.04) for independent review committee (IRC)-assessed cORR and 0.98 (0.53-1.82) for investigator (INV)-assessed cORR. The weighted hazard ratio (HR) comparing mobocertinib to amivantamab was 0.74 (0.51-1.07) for IRC-assessed PFS, 0.92 (0.57-1.48) for OS, and 0.59 (0.30-1.18) for INV-assessed DoR. Conclusion: MAIC analysis showed that mobocer tinib and amivantamab had similar efficacy in patients with NSCLC harboring EGFR ex20ins mutations whose disease progressed during or after platinum -based chemotherapy. These findings may benefit patients by supporting future treatment options.

Objectives: Mobocertinib, a novel oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is available for the treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mu-tations after platinum chemotherapy. We performed an indirect comparison of clinical trial data and real-world data (RWD) to determine the relative efficacy of mobocertinib vs. other treatments for these patients.Materials and methods: Data on the efficacy of mobocertinib from a phase I/II trial (NCT02716116) were compared to RWD from a retrospective study in 12 German centers using inverse probability of treatment weighting to adjust for age, sex, Eastern Cooperative Oncology Group score, smoking status, presence of brain metastasis, time from advanced diagnosis, and histology. Tumor response assessment was based on RECIST v1.1.Results: The analysis included 114 patients in the mobocertinib group and 43 in the RWD group. The confirmed overall response rate (cORR) according to investigator assessment was 0% for standard treatments and 35.1% (95% confidence interval [CI], 26.4-44.6) for mobocertinib (p < 0.0001). Compared to standard regimens in the weighted population, mobocertinib prolonged overall survival (OS, median [95% CI] = 9.8 [4.3-13.7] vs. 20.2 [14.9-25.3] months; hazard ratio [HR] = 0.42 [0.25-0.69], p = 0.0035), progression-free survival (PFS, median [95% CI] = 2.6 [1.5-5.7] vs. 7.3 [5.6-8.8] months; HR = 0.28 [0.18-0.44], p < 0.0001), and time to treatment discontinuation (median [95% CI] = 2.1 [1.2-3.1] vs. 7.4 [6.4-8.5] months; HR = 0.34 [0.18-0.65], p = 0.0004).Conclusion: Mobocertinib was associated with an improved cORR and prolonged PFS and OS compared to standard treatments for patients with EGFR ex20ins-positive NSCLC previously treated with platinum-based chemotherapy.

Efficacy of ponatinib-based treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) has not been compared to imatinib-based treatments in head-to-head clinical trials. We evaluated its efficacy versus imatinib-based regimens using a matching adjusted indirect comparison. Two ponatinib studies were used: the phase 2 MDACC study of ponatinib + hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in adult patients and the phase 2 GIMEMA LAL1811 study of ponatinib + steroids in patients > 60 years/unfit for intensive chemotherapy and stem cell transplant. Studies on imatinib as first-line treatment in adults with Ph + ALL were identified using a systematic literature search. Population adjustment was based on the prognostic factors and effect modifiers identified by clinical experts. Hazard ratios (HRs) were calculated for overall survival (OS) and odds ratios (ORs) for complete molecular response (CMR). The systematic literature search identified two studies (GRAAPH-2005 and NCT00038610) reporting the efficacy of first-line imatinib + hyper-CVAD and one study reporting the efficacy of first-line imatinib monotherapy induction + imatinib-based consolidation (CSI57ADE10). Ponatinib + hyper-CVAD prolonged OS and gave a higher CMR rate than imatinib + hyper-CVAD. The adjusted HR [95

Objectives: To assess the effect of patient preferences on the net clinical benefit (NCB) of an antiplatelet therapy for the secondary prevention of cardiovascular complications. Study Design and Setting: Risk equations were developed to estimate the individual predicted risk of key outcomes of antiplatelet treatment in patients with a prior myocardial infarction using the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and UK Office of National Statistics databases. Patient preferences for outcomes of antiplatelet therapies were elicited in a separate discrete choice experiment survey. Trial hazard ratios, relative to placebo, were used to calculate the per-patient NCB using equal or preference weighting of outcomes. Results: Risk equations were estimated using 31,941 adults in the Clinical Practice Research Datalink population, of which 22,125 were included in the benefit-risk assessment. The mean NCB was lower in the preference-weighted than in the equal-weighted analysis (0.040 vs. 0.057; P < 0.0001), but the direction of effect was unchanged by the weighting. In analyses stratified by the presence of bleeding risk factors, including preference weighting altered the ranking of subgroups by NCB. Conclusion: Patient preference weighting may have a significant effect on NCB and should be included in personalized benefit-risk assessments. (C) 2021 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA. and The Author(s). Published by Elsevier Inc.

Tafasitamab plus lenalidomide (TAFA + LEN) received accelerated US Food and Drug Administration approval and conditional European Medicines Agency approval for treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for autologous stem cell transplant. This study investigates the relative efficacy of TAFA + LEN versus comparator treatments. Matching-adjusted indirect comparisons (MAICs) of TAFA + LEN were performed using data from L-MIND, and comparator studies assessing rituximab-based combination therapies, including polatuzumab vedotin + bendamustine + rituximab (POLA + BR) bendamustine + rituximab (BR), and gemcitabine + oxaliplatin + rituximab (R-GEMOX) to provide relative efficacy estimates for overall survival (OS), progression-free survival (PFS), duration of response (DOR), objective response rate (ORR), and complete response rate (CRR). Patient-level data from L-MIND were weighted to match reported distributions of clinically validated prognostic factors and effect modifiers in comparator trials. MAIC results versus multiple BR studies were pooled using meta-analysis. MAICs were feasible versus POLA + BR and BR. Compared to POLA + BR, TAFA + LEN was associated with significantly longer DOR [hazard ratio (HR) 0.34 (95% CI 0.12, 0.98); p = 0.045]. Due to concerns about the proportional hazard assumption for OS and PFS, separate HRs were estimated before and after 4 months of follow-up. OS after 4 months, was significantly greater for TAFA + LEN versus POLA + BR [HR 0.41 (95% CI 0.19, 0.90); p = 0.026]. Compared with BR, TAFA + LEN was associated with significantly improved OS [GO29365 comparator trial: HR 0.39 (95% CI 0.18, 0.82); p = 0.014], PFS (pooled data: HR 0.39 (95% CI 0.29, 0.53); p < 0.001], DOR [pooled data: HR 0.35 (95% CI 0.25, 0.50); p < 0.001], and CRR [pooled data: odds ratio 2.43 (95% CI 1.33, 4.41); p = 0.004]. In MAIC analyses, treatment with TAFA + LEN for R/R DLBCL provided better OS and PFS outcomes than standard treatment regimens. Validation from large, randomized, phase 3 clinical trials is required to confirm these results. Tafasitamab in combination with lenalidomide has been recently approved for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma. There are no clinical trials to directly compare the outcomes of tafasitamab + lenalidomide against other treatments for diffuse large B-cell lymphoma. Matching-adjusted indirect comparisons allow an estimate of the relative efficacy of treatments to be derived in the absence of head-to-head comparisons from clinical trials. Matching-adjusted indirect comparisons analyses utilizing data from previously published clinical trials were conducted to compare the combination of tafasitamab + lenalidomide against 3 standard treatments for relapsed or refractory diffuse large B-cell lymphoma: polatuzumab vedotin + bendamustine + rituximab, bendamustine + rituximab, and rituximab + gemcitabine + oxaliplatin. Compared to those treated with polatuzumab vedotin + bendamustine + rituximab, patients treated with TAFA + LEN maintained their response to treatment for longer and are more likely to experience long-term survival. When compared to those treated with bendamustine + rituximab, patients treated with TAFA + LEN had increased survival, a higher level of response, and maintained their response to treatment for longer. Overall, the findings suggest that treatment with TAFA + LEN for R/R DLBCL is likely to result in significantly better outcomes compared with standard rituximab-based treatments.

9115 Background: Mobocertinib (mobo) and amivantamab (ami) are FDA-approved treatments for patients (pts) with locally advanced or metastatic NSCLC with EGFR ex20ins whose disease progressed on or after platinum-based chemotherapy. An unanchored MAIC was used to compare confirmed overall response rate (cORR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS) between mobo and ami. Methods: Clinical outcomes were compared in platinum-pretreated pts with EGFR ex20ins+ NSCLC treated with mobo 160 mg QD in a phase I/II single-arm study (NCT02716116, cut-off 1 Nov 2020, n=114) or with ami 1,050 mg (1,400 mg, ≥80 kg) in a phase I single-arm study (NCT02609776, cut-off 8 June 2020, n=81). Differences in baseline characteristics reported in both studies, including age, race, sex, smoking status, Eastern Cooperative Oncology Group, histology, sites of metastasis (brain, bone and liver), time from advanced diagnosis, number of prior lines of therapy, prior immuno-oncology therapy, prior EGFR tyrosine kinase inhibitor treatment and prior EGFR ex20ins targeted therapy, were adjusted with MAIC. Results: After MAIC weighting all reported baseline characteristics were balanced between mobo and ami. OS and cORR per investigator assessment (INV) were similar between mobo and ami (Table). cORR per independent review committee (IRC) was numerically higher for ami (odds ratio [OR]=0.64, p value=0.230). For PFS per IRC, the adjusted hazard ratio (HR) was numerically favorable for mobo (HR=0.82, p value=0.417). Among the responders, DoR was longer for mobo (DoR per INV: HR=0.44, p value=0.049; DoR per IRC: HR=0.56, p value=0.149). Conclusions: Mobo and ami appear to have overall similar efficacy. As each has a different mechanism of action and route of administration, they provide multiple options in the treatment of EGFR ex20ins+ NSCLC. Clinical trial information: NCT02716116. [Table: see text]

OBJECTIVES:Population-adjusted comparisons of progression-free survival (PFS) from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparisons (MAICs); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules. This study aims to assess the effects of assessment-schedule matching (ASM) on the relative effectiveness on the PFS of avelumab versus approved comparator immunotherapies or chemotherapy after population matching in the second-line (2L) setting for metastatic urothelial carcinoma.METHODS:The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004). PFS was compared with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The MAIC was repeated after conducting ASM for differences in tumor assessment scheduled first at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for other treatments.RESULTS:MAIC adjustment alone altered the HR estimates up to 23%, whereas MAIC plus ASM resulted in up to 32.7% reductions from naive comparisons. Even in cases in which MAIC had little effect, ASM brought an additional change of 11.1% to 15.4%. Overall, the HR range of avelumab versus other treatments changed from 0.83 to 1.25 for naive comparisons to 0.76 to 0.99 after ASM plus MAIC, numerically favoring avelumab.CONCLUSIONS:Small variations in assessment schedules can introduce bias in unanchored indirect treatment comparisons of interval-censored time-to-event outcomes. In this study, adjusted PFS was comparable across second-line urothelial carcinoma treatment options, numerically favoring avelumab versus immunotherapies and chemotherapy agents. Correcting this bias is especially important when HRs are applied in cost-effectiveness models to transition patients between states.

Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678). At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH). Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3–4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001). Single-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM.

To quantify the trade-offs people with migraine are willing to make between attributes of preventive treatments.

e20527 Background: Single-agent belantamab mafodotin (GSK2857916) is a first-in-class immunoconjugate targeting B-cell maturation antigen that demonstrated deep and durable responses in heavily pretreated patients with RRMM in the pivotal DREAMM-2 study (NCT03525678; Lancet Oncol 2020). Methods: DREAMM-2 included patients with late-line RRMM treated with ≥3 prior lines of therapy, refractory to an immunomodulatory agent and a proteasome inhibitor, with prior exposure to an anti-CD38 antibody. Evidence from Phase II/III trials in a similar patient population was systematically identified following PRISMA guidelines. Based on the specificity of the DREAMM-2 population, selinexor plus low-dose dexamethasone (sel+dex) was identified as the only feasible comparator (STORM Part 2, NCT02336815). Matching-adjusted indirect comparisons (MAIC) were used to investigate the efficacy of single-agent belantamab mafodotin vs. sel+dex. Populations were matched for all clinically validated effect modifiers and prognostic factors with available data. MAIC were performed for overall response rate (ORR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS), as per NICE guidelines. Results: Single-agent belantamab mafodotin was more efficacious than sel+dex in terms of OS and DoR (Table). Results for ORR, TTR, and PFS showed no statistical difference between the two regimens. Conclusions: MAIC of single-agent belantamab mafodotin vs. sel+dex in this patient population with RRMM showed significantly improved efficacy on OS and DoR for belantamab mafodotin. Further validation is required owing to limited data availability. Additional safety analyses will further inform comparisons of the two. Clinical trial information: NCT03525678; NCT02336815. Funding: GlaxoSmithKline (207145). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. [Table: see text]

573 Background: Population-adjusted comparisons of PFS from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparison (MAIC); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules (favoring longer intervals). This is shown with an MAIC of avelumab vs atezolizumab, nivolumab, durvalumab, pembrolizumab or chemotherapy in 2L UC. Methods: The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004) and compared PFS with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The first assessment was scheduled at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for the others. The MAIC was repeated after aligning the first assessment time for avelumab to each comparator’s schedule with the Assessment Schedule Matching (ASM) method. Results: Naïve analyses (Table) suggest similar PFS for avelumab vs comparators. MAIC based on population adjustment (PA) altered the HR of avelumab vs atezolizumab and nivolumab (23.0% and 9.2% reductions in HR, respectively) but had little effect in other comparisons. ASM adjustment led to further changes in HR (13.2-32.7% reductions from naïve) favoring avelumab in MAICs where schedules differed. Of note, assessment schedule differences fully accounted for differences in PFS between avelumab and pembrolizumab. Conclusions: Indirect comparisons of PFS from single-arm trials must include adjustment for differences in both population characteristics and tumor assessment schedules. In this 2L UC MAIC, adjustment reversed some naïve comparisons, revealing more favorable PFS with avelumab up to 30%. Clinical trial information: NCT01772004. [Table: see text]

Context: Patients with RRMM who have progressed following standard-of-care (SoC) regimens have limited treatment options. Single-agent belamaf demonstrated deep and durable responses in heavily pretreated patients with RRMM in the DREAMM-2 primary analysis (NCT03525678; Lonial et al. Lancet Oncol 2020). Objective: To indirectly compare the efficacy of single-agent belamaf versus appropriate comparators in similar patient populations (received ≥3 prior lines of treatment, refractory to anti-CD38 therapies) in a post-hoc analysis of DREAMM-2. Methods: Following a systematic literature review, STORM Part 2 (NCT02336815) study of selinexor+dexamethasone (sel+dex) was identified as a feasible comparator. Matching-adjusted indirect comparisons (MAIC) were performed to investigate the efficacy of single-agent belamaf (DREAMM-2) versus sel+dex (STORM) by matching populations for all available, clinically-validated effect modifiers, and prognostic factors (Popat et al ASCO 2020 e10527; EHA 2020 EP1016). Belamaf efficacy vs SoC was estimated by Bucher indirect treatment comparison (ITC) of MAIC results with the relative efficacy of sel+dex versus SoC in a patient subset# from MAMMOTH (retrospective, natural history study of patients with RRMM following SoC), evaluated against a comparable STORM subset (Costa et al. Blood 2019). Results: MAIC and Bucher ITC analyses suggested significantly longer overall survival (OS) with single-agent belamaf versus sel+dex (hazard ratio [HR] [95% CI]: 0.60 [0.39–0.94]; p=0.025) and SoC (HR [95% CI]: 0.33 [0.17–0.63]; p < 0.001). MAIC results suggested significantly longer duration of response (DoR) for belamaf (HR [95% CI]: 0.34 [0.13–0.90]; p=0.030) compared with sel+dex. Overall response rates (odds ratio [97.5% CI]: 0.95 [0.5–1.83]; p=0.88), time to response (HR [95% CI]: 0.76 [0.46–1.23]; p=0.26), and progression-free survival (HR [95% CI]: 1.34 [0.89–2.00]; p=0.16) were not statistically different. Conclusions: MAIC indicated significant improvements in OS and DoR with single-agent belamaf versus sel+dex in heavily pretreated RRMM patients. Subject to the shared treatment effect modifiers assumption, Bucher ITC suggested significantly improved OS with belamaf versus SoC. Additional analyses will inform safety comparisons. Funding: GlaxoSmithKline (207145). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. #Penta-exposed (bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab); refractory to ≥one proteasome inhibitor, one immunomodulatory agent, and daratumumab. Patients with RRMM who have progressed following standard-of-care (SoC) regimens have limited treatment options. Single-agent belamaf demonstrated deep and durable responses in heavily pretreated patients with RRMM in the DREAMM-2 primary analysis (NCT03525678; Lonial et al. Lancet Oncol 2020). To indirectly compare the efficacy of single-agent belamaf versus appropriate comparators in similar patient populations (received ≥3 prior lines of treatment, refractory to anti-CD38 therapies) in a post-hoc analysis of DREAMM-2. Following a systematic literature review, STORM Part 2 (NCT02336815) study of selinexor+dexamethasone (sel+dex) was identified as a feasible comparator. Matching-adjusted indirect comparisons (MAIC) were performed to investigate the efficacy of single-agent belamaf (DREAMM-2) versus sel+dex (STORM) by matching populations for all available, clinically-validated effect modifiers, and prognostic factors (Popat et al ASCO 2020 e10527; EHA 2020 EP1016). Belamaf efficacy vs SoC was estimated by Bucher indirect treatment comparison (ITC) of MAIC results with the relative efficacy of sel+dex versus SoC in a patient subset# from MAMMOTH (retrospective, natural history study of patients with RRMM following SoC), evaluated against a comparable STORM subset (Costa et al. Blood 2019). MAIC and Bucher ITC analyses suggested significantly longer overall survival (OS) with single-agent belamaf versus sel+dex (hazard ratio [HR] [95% CI]: 0.60 [0.39–0.94]; p=0.025) and SoC (HR [95% CI]: 0.33 [0.17–0.63]; p < 0.001). MAIC results suggested significantly longer duration of response (DoR) for belamaf (HR [95% CI]: 0.34 [0.13–0.90]; p=0.030) compared with sel+dex. Overall response rates (odds ratio [97.5% CI]: 0.95 [0.5–1.83]; p=0.88), time to response (HR [95% CI]: 0.76 [0.46–1.23]; p=0.26), and progression-free survival (HR [95% CI]: 1.34 [0.89–2.00]; p=0.16) were not statistically different. MAIC indicated significant improvements in OS and DoR with single-agent belamaf versus sel+dex in heavily pretreated RRMM patients. Subject to the shared treatment effect modifiers assumption, Bucher ITC suggested significantly improved OS with belamaf versus SoC. Additional analyses will inform safety comparisons.

Introduction: Standard treatments for older patients (pts) with acute myeloid leukemia (AML) can induce remission; however, responses are often short-lived and survival rates are poor upon relapse (Chen Y, et al. Medicine 2016;95:e4182). To date, no AML maintenance therapies have been approved by the US FDA, but a few have been used 'off-label'. Although some of these maintenance therapies, such as injectable azacitidine (AZA), improved disease-free survival in older pts with AML, overall survival (OS) benefits have been more difficult to achieve. Moreover, injectable therapies are associated with a higher administration burden and infusion reactions, and therefore may not be suitable for long-term maintenance therapy. The randomized, phase 3 QUAZAR AML-001 study (NCT01757535) of CC-486, a novel oral formulation of AZA, was the first maintenance study to demonstrate a significant and clinically meaningful improvement in OS (Wei AH, et al. Blood 2019;134:LBA-3). CC-486 was associated with a 9.9-month increase in OS (vs placebo) with a manageable safety profile and no compromise in health-related quality of life in pts with AML aged ≥ 55 years previously treated with intensive chemotherapy. Although previous research has examined patient preference for induction therapies, very little is known about preferences for AML maintenance therapies. We therefore used an online discrete choice experiment (DCE) survey to determine the relative importance that pts with AML place on key clinical benefits and risks, mode of administration, and out-of-pocket (OOP) costs. Methods: From November 2019 to April 2020, pts aged ≥ 55 years from the USA, Canada, Germany, and Italy who had undergone treatment for AML were invited to participate in an online DCE survey. Attributes in the DCE survey included clinical benefits (time until relapse [6, 12, 24 months] and 2-year survival rate [30%, 50%, 60%]), adverse events (risk of mild-to-moderate stomach problems [40%, 60%, 80%] and risk of serious infection [10%, 20%, 40%]), mode of administration (once-daily oral tablet for 14 or 21 consecutive days/month, subcutaneous [SC] injection in a clinic/hospital for 7 consecutive days/month, or intravenous [IV] infusion in a clinic/hospital for 5 or 7 consecutive days/month), and OOP costs (USD 200, 400, 800). Patient preferences for attribute levels were analyzed using a multinomial logit model and expressed as marginal utilities and maximum acceptable decrease in 2-year survival rate. Results: In total, 170 pts completed DCE surveys (USA, n = 104; Canada, n = 6; Germany, n = 30; and Italy, n = 30). Mean age was 63.0 years, and 54% of pts were male. In all, 73% of pts had achieved remission at any time, 74% had not received prior stem cell transplant, and 79% had been diagnosed with AML in the last 6 months. Based on the DCE survey results, pts valued a 30% increase in the chance of 2-year survival (marginal utility for 60% = 0.84; 95% confidence interval [CI] 0.70-0.99) more than changes in any other attribute. This was followed by a USD 600 decrease in OOP costs (marginal utility for USD 200 = 0.77; 95% CI 0.66-0.89), 18-month increase in time until relapse (marginal utility for 24 months = 0.61, 95% CI 0.48-0.74), an oral tablet for 14 days/month instead of IV infusion 7 days/month (marginal utility = 0.38, 95% CI 0.23-0.54), and a 30% decrease in the risk of serious infection due to injection (marginal utility for 10% = 0.20; 95% CI 0.09-0.32). Risk of mild-to-moderate stomach problems was not important to pts (Figure). Pts preferred an oral tablet taken either 14 or 21 days/month over SC injection 7 days/month (both P = 0.002). In addition, pts were willing to accept a 16% and 14% decrease in the chance of 2-year survival to switch from IV infusion in a clinic/hospital for 7 consecutive days/month to an oral tablet for 14 days/month (95% CI 9.95-22.08) or 21 days/month (95% CI 7.44-20.50), respectively. Conclusions: In this survey of pts with AML, the most important attribute during maintenance therapy was the probability of survival at 2 years. In addition, pts demonstrated a significant preference toward an oral tablet over IV infusions and SC injections in a clinic/hospital, and were willing to accept a significant decrease in treatment efficacy in favor of an oral mode of administration. This study provides valuable insights into patient preferences and may help inform decision-making for AML maintenance therapies. Disclosures Tervonen: Evidera: Current Employment, Current equity holder in publicly-traded company. Seo:Bristol Myers Squibb: Research Funding; Evidera: Current Employment. Nehme:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. La Torre:Bristol Myers Squibb: Current Employment. Prawitz:Bristol Myers Squibb: Research Funding; Evidera: Current Employment. Chen:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Beach:Bristol Myers Squibb: Current Employment. Wang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

Purpose: Quantitative benefit-risk (B-R) assessments are used to characterize treatment by combining key benefits and risks into a single metric but have historically been done for the average patient. Our aim was to conduct an individualized assessment for the oral antiplatelet vorapaxar by combining trial and real-world data to further personalize the treatment profiles. Methods: Using linked UK health care databases, we developed risk prediction equations for key ischemic and bleeding events using Cox proportional hazards models. Trial hazard ratios, relative to placebo, were applied to baseline risk estimates to compute expected attributable risks, summed to derive a per-patient net clinical benefit (NCB). High risk subgroups were defined a priori, and Gaussian mixture models (GMM) were fit to characterize the NCB distribution and identify subgroups with similar NCBs. Results: NCB was consistently positive for all subgroups, likely due to the outcome correlation, and would remain positive with a 12-fold increase in bleeding risk. GMMs identified three distinct NCB subgroups. Compared with the middle/lower NCB subgroups, those with a higher NCB tended to be older, female, and have higher CV disease burden. Conclusions: Personalized B-R assessments are feasible and clinically valuable and can be used to better predict who would benefit most from therapy.

Background The timing of efficacy-related clinical events recorded at scheduled study visits in clinical trials are interval censored, with the interval duration pre-determined by the study protocol. Events may happen any time during that interval but can only be detected during a planned or unplanned visit. Disease progression in oncology is a notable example where the time to an event is affected by the schedule of visits within a study. This can become a source of bias when studies with varying assessment schedules are used in unanchored comparisons using methods such as matching-adjusted indirect comparisons. Objective We illustrate assessment-time bias (ATB) in a simulation study based on data from a recent study in second-line treatment for locally advanced or metastatic urothelial carcinoma, and present a method to adjust for differences in assessment schedule when comparing progression-free survival (PFS) against a competing treatment. Methods A multi-state model for death and progression was used to generate simulated death and progression times, from which PFS times were derived. PFS data were also generated for a hypothetical comparator treatment by applying a constant hazard ratio (HR) to the baseline treatment. Simulated PFS times for the two treatments were then aligned to different assessment schedules so that progression events were only observed at set visit times, and the data were analysed to assess the bias and standard error of estimates of HRs between two treatments with and without assessment-schedule matching (ASM). Results ATB is highly affected by the rate of the event at the first assessment time; in our examples, the bias ranged from 3 to 11% as the event rate increased. The proposed method relies on individual-level data from a study and attempts to adjust the timing of progression events to the comparator’s schedule by shifting them forward or backward without altering the patients’ actual follow-up time. The method removed the bias almost completely in all scenarios without affecting the precision of estimates of comparative effectiveness. Conclusions Considering the increasing use of unanchored comparative analyses for novel cancer treatments based on single-arm studies, the proposed method offers a relatively simple means of improving the accuracy of relative benefits of treatments on progression times.