Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor.

INTRODUCTION: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) often require multiple lines of treatment and have a poor prognosis, particularly after failing covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. Newer treatments such as brexucabtagene autoleucel (brexu-cel, chimeric antigen receptor T cell therapy) and pirtobrutinib (non-covalent BTKi) show promise in improving outcomes. METHODS: Without direct comparative evidence, an unanchored matching-adjusted indirect comparison was conducted to estimate the relative treatment effects of brexu-cel and pirtobrutinib for post-cBTKi R/R MCL. Using logistic propensity score models, individual patient-level data from ZUMA-2 brexu-cel-infused population (N = 68) were weighted to match pre-specified clinically relevant prognostic factors based on study-level data from the BRUIN cBTKi pre-treated cohort (N = 90). The base-case model incorporated the five most pertinent factors reported in ≥ 50% of both trial populations: morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplant. A sensitivity analysis additionally incorporated TP53 mutation and Ki-67 proliferation. Relative treatment effects were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: In the base-case model, brexu-cel was associated with higher rates of objective response (OR 10.39 [95% CI 2.81-38.46]) and complete response (OR 10.11 [95% CI 4.26-24.00]), and improved progression-free survival (HR 0.44 [95% CI 0.25-0.75]), compared to pirtobrutinib. Overall survival and duration of response favored brexu-cel over pirtobrutinib but the differences crossed the bounds for statistical significance. Findings were consistent across the adjusted and unadjusted analyses. CONCLUSIONS: Findings suggest that brexu-cel may offer clinically and statistically significant benefits regarding objective response, complete response, and progression-free survival compared to pirtobrutinib among patients with R/R MCL after prior cBTKi therapy. Given the short follow-up and high degree of censoring in BRUIN, an analysis incorporating updated BRUIN data may provide more definitive overall survival results.

Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma.

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure.

Matching-Adjusted Indirect Comparisons of Brexucabtagene Autoleucel with Alternative Standard Therapies for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients.

INTRODUCTION: Brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, is approved for relapsed/refractory B-cell precursor acute lymphoblastic leukemia in adults aged 18+/26+ years in the US/European Union (EU), based on efficacy results from the single-arm ZUMA-3 trial. This study aimed to estimate the relative treatment effects of brexu-cel versus inotuzumab ozogamicin (InO), blinatumomab (blina), and chemotherapies using unanchored matching-adjusted indirect comparison (MAIC) methods. METHODS: Individual patient data from ZUMA-3 and published aggregate level data from two randomized controlled trials, INO-VATE (InO versus chemotherapy) and TOWER (blina versus chemotherapy), were used. Patient-level data from ZUMA-3 were weighted to match the mean of the following prognostic variables at baseline, which were pre-specified based on clinical input, for each comparator population: primary refractory disease, duration of first remission < 12 months, prior stem-cell transplantation, age, performance status, salvage status, bone marrow blast, complex karyotype, and Philadelphia chromosome status. The base case analysis was conducted using the modified intention-to-treat population (i.e., received brexu-cel) from ZUMA-3. Relative treatment effects for overall survival (OS) and event-free survival (EFS) were expressed as hazard ratios (HR) and differences in restricted mean survival time (RMST) with 95% confidence intervals (CI). RESULTS: The base case MAIC results suggested brexu-cel improved OS and EFS compared to blina (OS HR 0.46 [95% CI 0.28, 0.75]; EFS HR 0.37 [95% CI 0.25, 0.56]) and pooled INO-VATE/TOWER chemotherapy (OS HR 0.32 [95% CI 0.18, 0.56]; EFS HR 0.27 [0.18, 0.40]). Brexu-cel also improved OS compared to InO (HR 0.45 [95% CI 0.24, 0.85]). The point estimate for EFS favored brexu-cel over Ino but the difference was not statistically significant (HR 0.67 [95% CI 0.41, 1.10]). Findings were consistent between the HR and RMST analyses. CONCLUSION: Despite limitations, these MAIC results suggest that brexu-cel may improve OS and EFS versus currently used therapies in this population.

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study.

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6-20.0) in the overall cohort, 5.5 months (95% CI 3.9-8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9-30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3-12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure.

Matching-adjusted indirect comparison of axi-cel and liso-cel in relapsed or refractory large B-cell lymphoma.

In the absence of a randomized head-to-head trial, an unanchored matching-adjusted indirect comparison was performed to estimate the relative treatment effects of axicabtagene ciloleucel (axi-cel; ZUMA-1) versus lisocabtagene maraleucel (liso-cel; TRANSCEND-NHL-001) for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) after at least two lines of therapy. After matching, axi-cel and liso-cel had comparable objective response rates and duration. Compared to liso-cel, axi-cel was associated with improvements in overall survival (hazard ratio [HR]: 0.53 [95% CI: 0.34-0.82]) and progression-free survival (HR: 0.61 [95% CI: 0.40-0.92]). Axi-cel was associated with a higher rate of grade ≥3 cytokine release syndrome (odds ratio [OR]: 3.64 [95% CI: 1.04-12.76]) and neurological events (OR: 3.45 [95% CI: 1.65-7.19]), with smaller differences estimated in scenario analyses including ZUMA-1 safety management cohorts. Results suggest axi-cel improved survival compared to liso-cel but with increased odds of specific adverse events.

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

Background: For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010-2020. Methods: Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50-0.86), 1-12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04-2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54-1.10), 1-12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3-5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83-2.60)], immune-mediated AEs [1.75 (0.33-7.49)], and all-cause discontinuation due to AEs [1.21 (0.58-2.61)]. Conclusions: Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

Correlation Between Early Time-to-Event Outcomes and Overall Survival in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving Definitive Chemoradiation Therapy: Systematic Review and Meta-Analysis.

Background: Overall survival (OS) is the most patient-relevant outcome in oncology; however, in early cancers, large sample sizes and extended follow-up durations are needed to detect statistically significant differences in OS between interventions. Use of early time-to-event outcomes as surrogates for OS can help facilitate faster approval of cancer therapies. In locally advanced head and neck squamous cell carcinoma (LA-HNSCC), event-free survival (EFS) was previously evaluated as a surrogate outcome (Michiels 2009) and demonstrated a strong correlation with OS. The current study aimed to further assess the correlation between EFS and OS in LA-HNSCC using an updated systematic literature review (SLR) focusing on patients receiving definitive chemoradiation therapy (CRT). Methods: An SLR was conducted on May 27, 2021 to identify randomized controlled trials assessing radiotherapy alone or CRT in the target population. Studies assessing CRT and reporting hazard ratios (HRs) or Kaplan-Meier data for OS and EFS were eligible for the analysis. CRT included any systemic treatments administered concurrently or sequentially with radiation therapy. Trial-level EFS/OS correlations were assessed using regression models, and the relationship strength was measured with Pearson correlation coefficient (R). Correlations were assessed across all CRT trials and in trial subsets assessing concurrent CRT, sequential CRT, RT+cisplatin, targeted therapies and intensity-modulated RT. Subgroup analysis was conducted among trials with similar EFS definitions (i.e. EFS including disease progression and/or death as events) and longer length of follow-up (i.e.≥ 5 years). Results: The SLR identified 149 trials of which 31 were included in the analysis. A strong correlation between EFS and OS was observed in the overall analysis of all CRT trials (R=0.85, 95% confidence interval: 0.72-0.93). Similar results were obtained in the sensitivity analyses of trials assessing concurrent CRT (R=0.88), sequential CRT (R=0.83), RT+cisplatin (R=0.82), targeted therapies (R=0.83) and intensity-modulated RT (R=0.86), as well as in trials with similar EFS definitions (R=0.87), with longer follow-up (R=0.81). Conclusion: EFS was strongly correlated with OS in this trial-level analysis. Future research using individual patient-level data can further investigate if EFS could be considered a suitable early clinical endpoint for evaluation of CRT regimens in LA-HNSCC patients receiving definitive CRT.

Systematic literature review and network meta-analysis of pembrolizumab versus other interventions for previously untreated, unresectable or metastatic, MSI-high or MMR-deficient CRC.

Aim: To compare pembrolizumab with competing interventions for previously untreated, unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. Method: Trials were identified via a systematic literature review and synthesized using a Bayesian network meta-analysis with time-varying hazard ratios (HRs). Results: Using intention-to-treat data, HRs for overall survival were generally in favor of pembrolizumab but not statistically significant; however, statistical significance was reached versus all comparators by month 16 when accounting for crossover. Estimated HRs for progression-free survival significantly favored pembrolizumab versus all comparators by month 12. Pembrolizumab was also superior to all comparators in terms of grade ≥3 adverse events. Conclusion: These analyses suggest that pembrolizumab is a highly efficacious and safe treatment in this population.

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%. METHODS: A 30-year "partitioned survival" model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties. RESULTS: Cemiplimab was associated with increased time in the "preprogression" (13.08 vs 7.90 and 6.08 months) and "postprogression" (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI -0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy. CONCLUSIONS: Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer.

Objectives: In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression. Methods: Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring). Results: In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction-the most suitable method based on published guidelines and trial characteristics-produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction. Conclusions: After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.

Cost-effectiveness analysis of cemiplimab vs pembrolizumab for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: Most cutaneous squamous cell carcinomas (CSCCs) can be treated with surgical excision or radiation; however, approximately 1% of patients develop advanced disease. In 2018, the FDA approved cemiplimab-rwlc as the first programmed cell death-1 (PD-1) monoclonal antibody for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In June 2020, pembrolizumab, another PD-1 monoclonal antibody, was approved for the treatment of patients with recurrent or metastatic CSCC who are not candidates for curative surgery or radiation. We previously reported on the cost-effectiveness of cemiplimab vs historical standard of care for the treatment of advanced CSCC from a US perspective. OBJECTIVE: To estimate the cost-effectiveness of cemiplimab vs pembrolizumab for patients with advanced CSCC in the United States. METHODS: A "partitioned survival" framework was used to assess the cost-effectiveness of cemiplimab vs pembrolizumab. Clinical inputs were based on the most recent data cut of the phase 2 trials for cemiplimab (EMPOWER-CSCC-1; NCT02760498) and pembrolizumab (KEYNOTE-629). Progression-free survival and overall survival were extrapolated using parametric models until all patients had progressed or died. Health state utilities were derived from data collected in the EMPOWER-CSCC-1 trial. Costs included drug acquisition, drug administration, disease management, terminal care, and adverse events and were based on published 2020 US list prices. To assess model uncertainty, 1-way sensitivity and probabilistic sensitivity analyses (PSA) were conducted, alongside scenario analyses evaluating key modeling assumptions. RESULTS: In the base case, cemiplimab resulted in an incremental gain of 3.44 life-years (discounted) and incremental cost-effectiveness ratio (ICER) of $130,329 per quality-adjusted life-year (QALY) vs pembrolizumab. At a willingness-to-pay threshold of $150,000/QALY, PSA indicated a 71% probability that cemiplimab is cost-effective when compared with pembrolizumab. Scenario analysis resulted in ICERs ranging from $115,909 to $187,374. CONCLUSIONS: Findings suggest that cemiplimab is a cost-effective treatment for patients with advanced CSCC, compared with pembrolizumab. These results should be interpreted cautiously in the absence of head-to-head trials; however, in the absence of such data, these results can be used to inform health care decisions over resource allocation. DISCLOSURES: This study was supported by Regeneron Pharmaceuticals, Inc., and Sanofi. Paul, Cope, Keeping, Mojebi, and Ayers are employees of PRECISIONheor, which received funding to produce this work. Chen, Kuznik, and Xu are employees and stockholders of Regeneron Pharmaceuticals, Inc. Sasane is an employee and stockholder of Sanofi, Inc. Konidaris, Atsou, and Guyot are employees of Sanofi, Inc. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication.

Assessing the Value of Cemiplimab for Adults With Advanced Cutaneous Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the cost-effectiveness of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC) from a payer perspective in the United States. METHODS: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review, supplemented by expert opinion where necessary. Clinical inputs for cemiplimab were based on individual patient data from a cemiplimab phase 2 single-arm trial (NCT27060498). For SOC, analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via a systematic literature review (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. RESULTS: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio of $99 447 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372 108 and 3.74, respectively. At a willingness-to-pay threshold of $150 000/QALY, the probabilistic sensitivity analysis suggests a 90% probability that cemiplimab is cost-effective compared to SOC. Scenario analyses resulted in incremental cost-effectiveness ratios ranging from $90 590 to $148 738. CONCLUSIONS: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma.

Aim: To estimate the comparative efficacy of cemiplimab, a programmed cell death protein 1 inhibitor, versus EGFR inhibitors, pembrolizumab and platinum-based chemotherapy in terms of overall survival (OS) and progression-free survival. Patients & methods: We performed an indirect treatment comparison of cemiplimab and other available systemic therapies for patients with advanced cutaneous squamous cell carcinoma. Results: Cemiplimab was associated with benefits in OS (hazard ratios range: 0.07-0.52) and progression-free survival (hazard ratios range: 0.30-0.67) versus EGFR inhibitors and pembrolizumab (data from KEYNOTE-629). Cemiplimab was more efficacious versus platinum-based chemotherapy in terms of OS. Conclusion: Cemiplimab may offer improvements in survival for advanced cutaneous squamous cell carcinoma patients compared with existing systemic therapies.

Comparative effectiveness of nivolumab versus standard of care for third-line patients with small-cell lung cancer.

Aim: To estimate the comparative effectiveness of nivolumab versus standard of care (SOC) in terms of overall survival (OS) for small-cell lung cancer patients treated with two prior lines of chemotherapy, in other words, third line in the USA. Materials & methods: Data were from CheckMate 032, a single-arm trial of nivolumab, and real-world electronic patient records. Comparisons of OS were conducted using three different methods to adjust for differences (regression, weighting and doubly robust) between the populations. Results: Nivolumab was associated with longer survival compared with SOC (hazard ratio for OS: 0.58-0.70) across all methods for adjustment. Conclusion: Nivolumab was more efficacious in terms of OS as third-line treatment for small-cell lung cancer compared with current SOC in the USA.

Comparing Efficacy, Safety, and Preinfusion Period of Axicabtagene Ciloleucel versus Tisagenlecleucel in Relapsed/Refractory Large B Cell Lymphoma.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are autologous anti-CD19 chimeric antigen receptor T (CAR T) cell therapies for the treatment of patients with relapsed/refractory large B cell lymphoma (RR-LBCL). Both can induce durable responses; however, cross-trial comparisons are difficult due to differences in study design. In this study, the registration trials of axi-cel and tisa-cel were compared using a matching adjusted indirect comparison (MAIC). A MAIC was performed to adjust for differences in patient characteristics between trials. The estimates for the ZUMA-1 (axi-cel) trial were adjusted using patient-level data to match the study population in JULIET (tisa-cel) for key variables: International Prognostic Index), Eastern Cooperative Oncology Group score, stage, refractoriness or relapsed disease, double/triple hit status, cell of origin, and number of prior lines of therapy. The endpoints analyzed were response, overall survival (OS), and adverse events. After adjusting for differences in patient characteristics between trials, axi-cel was associated with a greater objective response rate (relative risk [RR]=1.61; 95% confidence interval [CI], 1.29 to 2.01) and complete response (RR = 1.62; 95% CI, 1.16 to 2.27) than tisa-cel among patients who underwent infusion. The OS from infusion onward comparing axi-cel to tisa-cel had a hazard ratio of 0.51 (95% CI, 0.31 to 0.83). The indirect comparison showed a higher rate of grade 1 to 2 cytokine release syndrome (CRS) in ZUMA-1 compared with JULIET (RR = 2.03; 95% CI, 1.55 to 2.65) and similar rates of grade ≥3 CRS and neurologic events. In the absence of a direct head-to-head study, the MAIC statistical technique suggests axi-cel may have superior efficacy but a greater risk of grade 1 to 2 CRS. Future real-world studies can further inform the relative efficacy and safety of CAR T therapies in RR-LBCL.

Indirect comparison of nivolumab ± ipilimumab (CheckMate 032) versus other treatments for recurrent small-cell lung cancer.

Aim: To estimate the comparative efficacy of nivolumab ± ipilimumab versus alternative treatments for small-cell lung cancer after at least one prior line of chemotherapy. Materials & methods: A systematic literature review identified six randomized controlled trials (RCTs) that could be connected in a network. The Kaplan-Meier survival curves from these RCTs were synthesized using network meta-analysis models. Aggregate-level matching was used to connect CheckMate 032 to the RCTs. Results: CheckMate 032 was connected to the network by Amrubicin Clinical Trial-1. Nivolumab ± ipilimumab had a more durable tumor response and more favorable long-term survival versus topotecan via intravenous and versus amrubicin. Conclusion: Compared with chemotherapies for recurrent small-cell lung cancer, nivolumab ± ipilimumab improves response duration, which may translate to long-term survival benefits.

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison.

BACKGROUND: There is significant unmet need among patients with relapsed and refractory classical Hodgkin's lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population. RESEARCH METHODS: The objective of this study was to compare progression-free survival (PFS) with standard of care (SOC) versus pembrolizumab in previously BV treated RRcHL patients. A systematic literature review identified one observational study of SOC that was suitable for comparison with KEYNOTE-087, the principal trial of pembrolizumab in this population. Both naïve and population-adjusted (using outcomes regression) pairwise indirect comparisons were conducted. The primary analysis included all patients who had failed BV, with a secondary analysis conducted including only those known to have failed BV that was part of definitive treatment. RESULTS: In the primary analysis, SOC was inferior to pembrolizumab in both the unadjusted comparison (HR 5.00 [95% confidence interval (CI) 3.56-7.01]) and the adjusted comparison (HR 6.35 [95% CI 4.04-9.98]). These HRs increased to 5.16 (95% CI 3.61-7.38) and 6.56 (95% CI 4.01-10.72), respectively, in the secondary analysis. CONCLUSION: Pembrolizumab offers a significant improvement in PFS compared to SOC in this population.

Penile cancer treatment costs in England.

BACKGROUND: Penile cancer is a rare malignancy in Western countries, with an incidence rate of around 1 per 100,000. Due to its rarity, most treatment recommendations are based on small trials and case series reports. Furthermore, data on the resource implications are scarce. The objective of this study was to estimate the annual economic burden of treating penile cancer in England between 2006 and 2011 and the cost of treating a single case based on a modified version of the European Association of Urology penile cancer treatment guidelines. METHODS: A retrospective (non-comparative) case series was performed using data extracted from Hospital Episode Statistics. Patient admission data for invasive penile cancer or carcinoma in situ of the penis was extracted by ICD-10 code and matched to data from the 2010/11 National Tariff to calculate the mean number of patients and associated annual cost. A mathematical model was simultaneously developed to estimate mean treatment costs per patient based on interventions and their associated outcomes, advised under a modified version of the European Association of Urologists Treatment Guidelines. RESULTS: Approximately 640 patients per year received some form of inpatient care between 2006 and 2011, amounting to an average of 1,292 spells of care; with an average of 48 patients being treated in an outpatient setting. Mean annual costs per invasive penile cancer inpatient and outpatient were £3,737 and £1,051 respectively, with total mean annual costs amounting to £2,442,020 (excluding high cost drugs). The mean cost per case, including follow-up, was estimated to be £7,421 to £8,063. Results were sensitive to the setting in which care was delivered. CONCLUSIONS: The treatment of penile cancer consumes similar levels of resource to other urological cancers. This should be factored in to decisions concerning new treatment modalities as well as choices around resource allocation in specialist treatment centres and the value of preventative measures.

The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review.

Since the 2008 introduction of the human papillomavirus (HPV) vaccination programme for adolescent girls in the UK, parents and other groups have expressed fears that immunisation condones sexual activity, promotes promiscuity and encourages risky sexual behaviour. This study aimed to explore whether HPV vaccination programmes have increased knowledge surrounding HPV and associated disease and whether uptake has influenced sexual behaviour. MEDLINE, Embase, Cochrane Library and PsycINFO electronic databases were interrogated. Studies of behaviour, attitudes and knowledge associated with HPV vaccination (or vaccination intent) in subjects of any age and gender in programmes reflective of UK practice were included in the review (n = 58). The evidence regarding the association of HPV vaccination with high-risk sexual behaviour was varied, primarily due to the heterogeneous nature of the included studies. Young females typically exhibited better knowledge than males, and vaccinated respondents (or those with vaccination intent) had higher levels of knowledge than the unvaccinated. However, knowledge surrounding HPV and genital warts was generally poor. This review highlights the need to provide effective education regarding the HPV vaccine and HPV-associated disease to adolescents of vaccination age, nurses, teachers, parents and guardians to ultimately allow informed decisions to be made regarding receipt of the HPV vaccine.