BACKGROUND AND OBJECTIVE:First-line (1L) treatment options for locally advanced or metastatic urothelial carcinoma (la/mUC) include enfortumab vedotin plus pembrolizumab (EV+P), based on EV-302, or platinum-based chemotherapy (PBC) with avelumab maintenance for patients without progression, based on JAVELIN-Bladder 100 (JB-100). Clinicians must choose between EV+P and PBC without knowing whether patients will respond to PBC and qualify for avelumab. In EV-302, avelumab maintenance was approved after trial initiation and therefore, was potentially underutilized among patients without progression. This modeling study facilitated a true 1L comparison of EV+P versus PBC ± avelumab. METHODS:Progression-free survival and overall survival were compared using EV-302 patient-level data and JB-100 study-level data. The JB-100 hazard ratio (HR) for avelumab versus best supportive care was applied to a comparable EV-302 PBC subgroup of patients without progression after a 22-week 1L period. This replaced EV-302 data for patients without progression to reflect outcomes assuming all EV-302 patients without progression received avelumab as observed in JB-100. Using a weighted hazard approach, patients without progression were combined with EV-302 patients with progression to obtain a hybrid PBC ± avelumab arm, which was compared with observed EV+P outcomes. Weighted average HRs with 95% confidence intervals (CIs) were calculated. KEY FINDINGS AND LIMITATIONS:EV+P improved progression-free survival (HR 0.51, 95% CI 0.44-0.59) and overall survival (HR 0.64, 95% CI 0.49-0.86) versus PBC ± avelumab. Results were consistent across sensitivity analyses. Limitations include assuming all patients without progression received avelumab, which may not reflect real-world patterns. CONCLUSIONS AND CLINICAL IMPLICATIONS:EV+P provides progression-free survival and overall survival benefits over PBC ± avelumab, reinforcing its position as the 1L standard of care in patients with la/mUC.

Olutasidenib and ivosidenib are isocitrate dehydrogenase 1 (IDH1) inhibitors approved for relapsed/refractory (R/R) IDH1 mutant (IDH1m) acute myeloid leukemia (AML). A matching-adjusted indirect comparison estimated relative treatment effects using registrational Phase I/II data for olutasidenib (Study 2102-HEM-101; individual patient data) and ivosidenib (Study AG120-C-001; study-level data) since a head-to-head trial is unlikely. Weights were estimated using a logistic propensity score model adjusted for pre-defined covariates identified from a literature review, validated by clinical experts. Eight covariates were determined to be the most important prognostic factors/effect modifiers for the target population as reported in the Food and Drug Administration labels: number of prior systemic therapies, age, prior hematopoietic stem cell transplantation, AML type, relapse type, cytogenetic risk, Eastern Cooperative Oncology Group performance status, and IDH1 mutation. Olutasidenib versus ivosidenib adjusted rates of complete remission (CR; odds ratio [OR] 1.12, 95

Background: Teclistamab (TEC) is the first B-cell maturation antigen-directed bispecific antibody approved in 2022 by the European Medicines Agency and Food and Drug Administration for triple-class exposed relapsed/refractory multiple myeloma (RRMM). Objectives: As TEC is increasingly used in real-world (RW) settings, this study seeks to gather existing RW evidence on effectiveness, safety, healthcare resource utilization, and clinical practices associated with TEC. Methods: A systematic literature review was performed to identify RW observational studies of TEC-treated adults with RRMM from 2023 to June 2024. Results: Sixty-one records representing 41 unique studies were included; sample sizes ranged from 8 to 572 patients. Where reported, median follow-up ranged from 2.3 to 33.6 months, and >65% of the patients would have been ineligible for the pivotal trial of TEC (MajesTEC-1) in all but one study. In eight studies with ≥50 patients and ≥3 months follow-up, overall response rates were 59–66% and cytokine release syndrome (CRS) rates were 18–64%. Tocilizumab use for CRS management was reported in 14 studies, with two indicating CRS rates of 13% and 26% when used prophylactically. Survival and infection outcomes showed wide variability due to short follow-up in most studies. Conclusions: Overall, early RW effectiveness and safety outcomes of TEC were comparable to findings from MajesTEC-1.

BackgroundAgalsidase beta is used to treat Fabry disease (FD); however, data on cardiac and cerebrovascular outcomes with agalsidase beta treatment come from studies with limited numbers of patients.MethodsA systematic literature review of studies reporting on the efficacy and effectiveness of agalsidase beta in FD was conducted. Studies were identified in searches of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from January 2000–June 2022. Outcomes of interest included cardiac structure and mass, cardiac events, and cerebrovascular events.ResultsFifty-two citations (41 studies) were included. Reductions in interventricular septal thickness (IVST) and/or left ventricular posterior wall thickness (LVPWT) were demonstrated in six studies (follow-up 1–6 years, n = 4 using echocardiography, n = 2 cardiac MRI). IVST ranged from 12.1–14.9 mm at baseline and 10.8–14.1 mm at follow-up (all p < 0.05). LVPWT ranged from 11.7–16.0 mm at baseline and 10.7–13.0 mm at follow-up (all p < 0.05). Significant reductions in cardiac mass were demonstrated after 1 year of treatment in a single-arm study using cardiac MRI [left ventricular mass (LVM) 193–178 g; LVM index 102–94 g/m2; both p < 0.05]. Rates of composite cardiac events (3.8%–24.0%; four studies, follow-up 2–10 years) and cerebrovascular events (0.0%–18.9%; 12 studies, follow-up 1–10 years) were numerically lower than rates for placebo (follow-up 3 years).ConclusionLiterature over the last 20 years indicates that agalsidase beta treatment may lead to stabilization or regression of cardiac structural thickness and mass, and reduction in cardiac and cerebrovascular events relative to placebo.

Purpose/Objective(s)Lurbinectedin received accelerated approval from the US Food and Drug Administration in 2020 for patients with metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy based on the results of a single-arm phase 2 basket trial . In this trial, lurbinectedin demonstrated an overall response rate (ORR) of 35.2% and a median overall survival (OS) of 9.3 months. Here, we performed an indirect treatment comparison of lurbinectedin vs relevant second-line treatments for SCLC by means of a network meta-analysis (NMA).Materials/MethodsA systematic literature review (1990–Jan 2021) identified 3 randomized controlled trials (RCTs) of second-line SCLC therapies recommended by NCCN guidelines that met the criteria for the NMA. Unanchored matching-adjusted indirect comparison (MAIC) connected Study B-005 to the network of RCTs. The RCT with the most overlap with Study B-005 was used as the target population in the base case, and a MAIC was performed to estimate the relative treatment effect of lurbinectedin vs oral topotecan (central node of the network). Relative treatment effects from the MAIC were used as direct evidence in the NMA. Analyses were conducted in a Bayesian framework for OS and ORR using a fixed-effect NMA, and relative effectiveness was assessed with hazard ratios (HR) and odds ratio.ResultsThe 3 RCTs included in the NMA were Baize 2020 (carboplatin/etoposide vs oral topotecan), and Eckardt 2007 and von Pawel 2001 (oral topotecan vs IV topotecan). In the base case, Baize 2020 was the target population, which consisted only of patients with platinum-sensitive disease (chemotherapy-free interval ≥90 day); therefore, the platinum-sensitive subgroup of Study B-005 was connected to the network. In the base case analysis, the HR for OS significantly favored lurbinectedin vs oral topotecan, IV topotecan, and carboplatin/etoposide (Table). There was a significant improvement in ORR for lurbinectedin vs oral topotecan; the ORR was similar for lurbinectedin vs carboplatin/etoposide (Table). Two sensitivity analyses were also conducted.ConclusionIn the absence of head-to-head RCTs, indirect treatment comparisons provide a means of estimating the relative efficacy of lurbinectedin vs relevant comparators for the second-line treatment of SCLC. In this NMA, lurbinectedin showed a robust survival benefit for the second-line treatment of platinum-sensitive patients with SCLC compared with platinum rechallenge and vs oral and IV topotecan. Study B-005; NCT02454972

ObjectivesIn 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.MethodsPatients 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).ResultsIn 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.ConclusionsAfter 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.

Lurbinectedin received accelerated FDA approval for patients with metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy based on results from a single-arm basket trial (NCT02454972). We conducted a systematic literature review (SLR) to evaluate clinical trials of second-line SCLC therapies recommended by NCCN Guidelines and assessed the feasibility of an indirect treatment comparison (ITC) to estimate relative efficacy and safety of lurbinectedin versus relevant comparators. Predefined searches of published and unpublished data were executed on January 6, 2021. Eligible non-randomized and single-arm trials were included only when comparative randomized controlled trials (RCTs) were unavailable for an intervention of interest. Two independent reviewers conducted abstract/full-text selection and data extraction. Of 4,769 citations identified, 10 unique relevant trials were included (5 RCTs, 2 single-arm trials, 2 RCTs with 1 arm of interest, and 1 with randomized and non-randomized cohorts with 1 arm of interest). Although there were differences in proportions of patients with sensitive/resistant disease, ECOG status, and limited/extensive disease, other baseline characteristics were generally consistent. Nine trials included patients with both limited- and extensive-stage disease at diagnosis. Three trials enrolled patients with platinum-sensitive disease (chemotherapy-free interval [CTFI] ≥90 days), 6 trials included patients with sensitive and resistant disease (CTFI <90 days); 1 trial did not report sensitivity. Only 5 trials included >10% of patients with resistant disease. In platinum-sensitive disease, median overall survival was between 5.8 and 8.1 months for topotecan (IV or oral), 7.5 months for platinum-rechallenge, and 11.9 months for lurbinectedin. These SLR results suggest that an ITC is feasible, as required assumptions are not prohibitive. Population-adjusted ITCs are required to adequately compare lurbinectedin with other treatments, given the inclusion of several disconnected single-arm trials. Restricting the ITC to patients with platinum-sensitive disease (CTFI ≥90 days) would reduce heterogeneity.

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 from January 2010 to November 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.

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%.

"HSR21-057: Cost-Effectiveness of Cemiplimab vs Pembrolizumab for the First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer (aNSCLC) and Programmed Death-Ligand 1 (PD-L1) Expression ≥50% in the US" published on 17 Mar 2021 by National Comprehensive Cancer Network.

e18817 Background: Cemiplimab monotherapy (mono) demonstrated significant survival benefit versus chemotherapy (CT) in the first-line (1L) treatment of advanced NSCLC with PD-L1 ≥50%. This analysis estimated the BI of introducing cemiplimab in the US from the healthcare payer’s perspective, in the context of available treatments. Methods: Cohorts of patients (pts) with advanced NSCLC and PD-L1 ≥50% without EGFR/ ALK mutations were modeled over 3 years (yrs). Treatment duration inputs were based on median progression-free survival (PFS) from EMPOWER-Lung 1 trial for cemiplimab and CT, and published data on median PFS for other immuno-oncology (IO) agents. Market shares were based on market research and assumed the following distribution in the scenario without cemiplimab: 68% pembrolizumab (pembro); 15% pembro + CT; 6% durvalumab (durva); 4% platinum CT; 3% atezolizumab (atezo); 2% nivolumab (nivo); and 2% nivo + ipilimumab (ipi). Cemiplimab market share was assumed to increase from 1% (yr 1), to 6% (yr 2), to 10% (yr 3). The analysis assumed that 50% of the cemiplimab market share will come from displacement of pembro mono, whilst the other 50% will come from displacement of platinum CT, atezo, durva, nivo, and nivo + ipi. The market share for pembro + CT was assumed to remain the same in both scenarios. Monthly list price of cemiplimab was lower than pembro and nivo at the time of this research and were sourced from ProspectoRx drug pricing database. Adverse event costs were estimated using HCUP 2017 data and ICD-10 codes specific to each event and inflated to 2019 costs using medical inflation indices from Bureau of Labour Statistics. Disease management costs were per Centers for Medicare and Medicaid Services data. In univariate sensitivity analyses, inputs were varied by ±20% to model the impact on total incremental costs over 3 yrs. Results: In a hypothetical US healthcare plan of 1,000,000 members, ̃60 were eligible to receive 1L cemiplimab treatment for advanced NSCLC with PD-L1 ≥50% in yr 1. The average incremental cost per member per month was $0.0038. The 3-yr incremental cumulative BI of cemiplimab was $138,463, representing a 0.561% increase in the healthcare payer’s 3-yr expenditures on these 60 pts. The incremental cost of adding cemiplimab was $8,744 in yr 1; $50,187 in yr 2; and $79,533 in yr 3. The analysis was most sensitive to changes to the treatment duration for cemiplimab (±172%) and pembro (±93%). Changes to all other inputs had < 20% impact. Conclusions: Cemiplimab is likely to be associated with a minimal increase in the budget for 1L treatment of advanced NSCLC with PD-L1 ≥50%. With a numerically lower list price relative to pembro and nivo, BI of cemiplimab was driven by the treatment duration for cemiplimab, which was higher than comparator treatments due to increased PFS.

e21091 Background: For advanced NSCLC patients (pts) with high (≥50%) PD-L1 expression, effective IO mono options with survival benefits are approved (pembrolizumab mono, current standard of care) and emerging (cemiplimab). In a recent Phase 3 trial, cemiplimab, a high-affinity, highly potent human PD-1 inhibitor approved for tx of advanced cutaneous squamous cell carcinoma, demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) vs chemotherapy (CT) in advanced NSCLC pts with PD-L1 ≥50%. A systematic literature review and NMA were conducted to identify/compare the efficacy/safety from randomized controlled trials (RCTs) for cemiplimab vs pembrolizumab or other IO mono published 2010–19. Methods: Relevant RCTs were identified by searching Embase, MEDLINE, Cochrane, and conference proceedings with predefined search strategies according to ISPOR, NICE, and PRISMA guidelines. An NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR), Grade (G) 3–5 all-cause adverse events (AE), G3–5 immune-mediated AE (IMAE) and discontinuation due to AEs (DAE). Fixed-effect models were used due to limited evidence. Results with standard constant HRs and various sensitivity analyses were conducted to account for differences in RCT designs and other txs. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded since an incompatible PD-L1 assay (SP142) was used for pt selection. For 1L advanced NSCLC with PD-L1 ≥50%, cemiplimab was associated with significantly greater PFS and ORR, and comparable OS, G3–5 AEs, IMAEs, and all-cause DAEs vs pembrolizumab (Table). At 2 yrs, numerically more pts receiving cemiplimab vs pembrolizumab were alive (59% vs 49%) and significantly more were alive w/o progression (37% vs 18%). Conclusions: In advanced NSCLC pts with PD-L1 ≥50%, cemiplimab mono demonstrated significant improvements in PFS and ORR, and comparable OS, safety/tolerability vs pembrolizumab.[Table: see text]

Podocytes are highly differentiated visceral cells, and several related specific proteins, such as podocalyxin and podocin are potential tools for the evaluation of podocyturia. However, precise quantitation of podocyturia-related proteins is complex and often unreliable.A reversed-phase ultra-performance liquid chromatography coupled to tandem mass spectrometry method was developed and validated to quantify podocalyxin and podocin levels in urine supernatant by using specific cleavable peptides and standards. Urine samples from women with normotensive or hypertensive pregnancies, gestational diabetes and preeclampsia, as well as treated and untreated Fabry patients, and gender-matched controls were investigated.The multiplex analysis shows that podocalyxin levels were higher than podocin levels in patients, the former being particularly higher in pregnant women. Women with preeclampsia had abnormal urine levels of both proteins with a higher sensitivity for podocalyxin. Slightly increased levels of podocin were also observed in Fabry males, while both proteins were increased in untreated Fabry females. Correlations were established between podocalyxin and podocin levels and clinical parameters associated with Fabry disease and preeclampsia.This methodology makes possible the precise, simultaneous and reliable analysis of podocalyxin and podocin levels, and offers a valuable tool for the evaluation of podocyturia.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT.Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24–120).In 69 patients (42 males, 27 females, mean age 44.6 ± 13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242–128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤ 60 ml/min/1.73 m2 (log Rank 12.423, p = 0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p = 0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models.GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.El objetivo de este estudio es realizar un mapa del tratamiento actual de la enfermedad de Fabry en España, analizando el efecto de diferentes factores en el desarrollo de eventos clínicos a largo plazo.Análisis observacional retrospectivo multicéntrico. Criterios de inclusión: pacientes diagnosticados y tratados de enfermedad de Fabry. Se recogieron datos generales en relación con el diagnóstico, síntomas y tipo mutación, tipo de tratamiento recibido, evolución renal y cardiológica. Durante un tiempo de seguimiento de 60 meses (24-120), se recogió el primer evento clínico tras el inicio de tratamiento sustitutivo enzimático definido como mortalidad, evento renal, cardiológico o neurológico.Se incluyeron 69 pacientes (42 H, 27 M) con una edad media de 44,6 ± 13,7 años. A los cinco años de tratamiento, el FGe y la hipertrofia ventricular izquierda se mantuvieron estables, y la albuminuria tiende a disminuir, siendo este descenso más significativo en el grupo de pacientes tratados con beta-galactosidasa (de 242 a 128 mg/g (p = 0,05). Veintiún pacientes sufrieron un evento clínico (30%): seis renales, dos neurológicos y 13 cardiológicos (incluidas tres muertes). Los pacientes con ERC (FGe < 60) antes del inicio de tratamiento tuvieron más eventos (log-rank 12.423, p = 0,001), manteniéndose la predicción si excluíamos los eventos renales (log-rank 4.086 (p = 0,043) en hombres y mujeres. La peor función renal al inicio del tratamiento aumentó entre tres y siete veces el riesgo de eventos clínicos en diferentes modelos de Cox ajustados.La función renal al inicio de tratamiento sustitutivo enzimático es la principal predictora de desarrollo de eventos clínicos a largo plazo, tanto en hombres como mujeres. El inicio de tratamiento sustitutivo enzimático precoz antes del desarrollo de ERC mejoraría el pronóstico.

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.