Summary
What is known and Objective
Psoriatic arthritis is an autoimmune disease characterized by chronic inflammation of the skin and joints. Anti‐TNF drugs reduce the severity of the disease in the ...long term. This study compares the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in patients with psoriatic arthritis.
Methods
Direct comparison was based on a literature search of drug comparison studies, whereas indirect treatment comparison was based on phase III clinical trials with biological agents, involving similar populations and durations, and with the same outcome. ACR50 was taken as primary outcome for comparison, whereas ACR20 and ACR70 were used as secondary outcomes. Indirect comparisons were made using infliximab as the reference drug and the Bucher method. In calculating δ (the maximum acceptable difference as a clinical criterion of equivalence), use was made of half of the absolute risk reduction obtained in the meta‐analysis of the clinical trials included in the indirect comparison (ARR 32%; δ: 16%). The four anti‐TNF drugs were also compared in relation to the secondary outcomes and adverse effects.
Results and Discussion
Reported direct and indirect comparisons of the four drugs did not include golimumab, and did not yield conclusive results. Four clinical trials – one for each drug studied – were identified. The estimated differences for the primary outcome, ACR50, between infliximab and the other drugs were adalimumab (ARR 4%, 95% CI −9·5 to 17·5), etanercept (ARR 4%, 95% CI −10·5 to 18·5) and golimumab (ARR 9%, 95% CI −5·4 to 23·4). Likewise, there were no relevant differences between the drugs in relation to the secondary efficacy outcomes, except for etanercept, which was less effective in ACR70 response. For adverse reactions, there were also no significant differences except for injection site, reactions which were more frequent with etanercept, with a mean difference of 26% relative to infliximab.
What is new and Conclusion
No significant differences were found in ACR50 responses to the four drugs after 24 weeks. Injection‐site reactions were more common with etanercept, but this was insufficient to invalidate the inference that clinically the four drugs can be regarded as clinically equivalent for the treatment of psoriatic arthritis.
Background and ImportanceAbemaciclib in combination with endocrine therapy (ET) has recently been authorised for adjuvant treatment of patients with human epidermal growth factor receptor 2 (HER2) ...negative and luminal early breast cancer (EBC) at high risk of recurrence.Aim and ObjectivesTo assess the comparative efficacy between abemaciclib and palbociclib in HER2-negative, high risk of recurrence and luminal EBC patients and to establish whether these drugs can be considered equivalent therapeutic alternatives (ETA), through an adjusted indirect treatment comparison (ITC).Material and MethodsA bibliographic search was conducted to identify phase III clinical trials with abemaciclib or palbociclib as adjuvant treatment in a similar EBC population (luminal type, HER2-negative and high risk of recurrence), duration and endpoints. The primary endpoint was invasive disease-free survival (IDFS) and ET was used as a common comparator. Similar clinical trials, consistent results and efficacy demonstration against the common comparator (ET) were required for the adjusted ITC.ResultsTwo trials were included, one of each drug. Both of them were phase III trials, randomised, in patients with HER2-negative, high risk and luminal EBC. Differences were found in the trial design (abemaciclib open-label vs palbociblib double-blind), number of patients included (abemaciclib N=5637 vs palbociclib N=1250), treatment duration (abemaciclib two years vs palbociclib one year) and percentage of patients pretreated with taxane, anthracycline or both (abemaciclib 37% vs palbociclib 99%). Clinical trials were not similar due to these differences.Abemaciclib was effective in HER2-negative, high risk and luminal EBC. However, palbociclib was not. IDFS abemaciclib group was statistically significant (HR=0.70; 95% CI: 0.59-0.82; p<0.0001) with a median follow-up of 27 months (90% patients completed treatment). In contrast, IDFS palbociclib group was not statistically significant (HR=0.93; 95% CI: 0.74-1.17; p=0.525) with a median follow-up of 43 months (92% patients completed treatment).Regarding consist results, 2-year IDFS rate was different too: abemaciclib 93% vs palpociclib 88%. In short, relevant methodological limitations were detected so adjusted ITC was not possible.Conclusion and RelevanceAbemaciclib and palbociclib cannot be considered ETA in HER2-negative, high risk and luminal EBC, although abemaciclib demonstrated efficacy as adjuvant treatment in these patients.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Background and importancePembrolizumab in monotherapy (in patients with PD-L1 expression ≥50%) or in combination with platinum-based chemotherapy (CT) (PDL-1 <50%) is the new standard therapy in ...first-line treatment of advanced or metastatic non-small cell lung cancer (mNSCLC).Aim and objectivesThe aim of this study was to determine whether the incidence of immune-related adverse events (irAEs) following the use of pembrolizumab in first-line mNSCLC is associated with clinical outcomes in real-world practice.Material and methodsAn observational, retrospective study was carried out, including patients with mNSCLC treated with pembrolizumab in first-line, between 1 January 2017 and 1 January 2021. Baseline patient characteristics were collected. To assess treatment effectiveness, the overall survival (OS) and progression-free survival (PFS) were measured. irAEs were categorised. OS and PFS were calculated for the population with any irAEs of any grade (irAEs+) and compared to patients without irAEs (irAEs–) in order to test our hypothesis.ResultsThe study included 62 patients with the following characteristics: mean age 67.44 years, majority of men (77.42%), smoking history (47% former smokers, 45% smokers), adenocarcinoma (87%), ECOG/PS-1=50%, ECOG/PS-0=38% and ALK/ROS-1/EGFR negative (89%), PD-L1 ≥50% (N=31), PDL-1 <50% (N=27) and unknown (N=4). Half of the patients received pembrolizumab alone and half received pembrolizumab in combination with CT. Most patients discontinued treatment due to progression (75.81%). irEAs (N=164) were observed in 77.4% of patients. In Kaplan–Meier analysis, median OS for overall, irAEs+ (N=48) and irAE– population (N=14) were as follows: 10.6 (95% CI 8.2 to 13.05), 10.9 (95% CI 8.6 to 13.2) and 4.4 months (95% CI 0 to 15.3), respectively. Median PFS for overall, irAEs+ and irAE– population were: 7.4 (95% CI 4.6 to 10,3), 8.7 (95% CI 5.9 to 11.6) and 2.3 months (95% CI 0 to 11.7), respectively. There were no significant differences in PFS and OS among the different populations.Conclusion and relevanceOur population did not reach statistical significance in the association between the presence of irEAs and clinical benefit. This may be due to the limited sample size.References and/or acknowledgements1. Hussaini S, et al. Association between immunerelated side effects and efficacy and benefit of immune checkpoint inhibitors – a systematic review and meta-analysis. Cancer Treat Rev 2021;92:102134. doi:10.1016/j.ctrv.2020.102134.Conflict of interestNo conflict of interest
Summary
What is known and objective
Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse ...the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)‐based method.
Comment
In the pivotal trial, pomalidomide plus low‐dose dexamethasone showed a significant survival benefit over high‐dose dexamethasone, with a difference between medians of 4·6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2·6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61·5% of patients for whom the time to event is reliable enough.
What is new and conclusion
This 2‐month differential would have major clinical and pharmacoeconomic implications, on both cost‐effectiveness studies and on the willingness of the healthcare systems to pay for this treatment.
Background and importanceThe SARS-CoV-2 pandemic could have changed the clinical management of cancer patients because of travel restrictions, overloading of hospital systems and disruption of ...treatment. Lung cancer patients constitute a vulnerable population due to the particular risk of their disease, chemotherapy or immunotherapy.Aim and objectivesTo analyse disease management and the clinical impact of the COVID-19 pandemic on non-small cell lung cancer (NSCLC) patients receiving intravenous treatment during the social isolation period compared with the normal situation.Material and methodsThis retrospective observational cohort study included a 2:1 random sample of NSCLC patients in the ‘COVID cohort’ (patients in isolation February 2020 to June 2020) and the ‘no COVID cohort’ (patients treated between February 2019 and June 2019). Collected variables from digital clinical history were age, sex, stage, previous lines, type of treatment, number of medical visits and telephone consults, cycles received, worsening of performance status (PS), respiratory infection (COVID-19 and others), delays, therapeutic rest break, disease progression and deaths.ResultsCOVID cohort (CC): 40 patients, 31 (78%) men; mean 67 years (59–84). Cancer stage: IV (69%), IIIB (28%), IIIA (2%) and IIIC (1%). 12 (30%) patients had not received lines previously. 38% of the population received immunotherapy. Median number of medical visits was 3 (14–1) and median number of telephone consults was 3 (1–8). Median number of cycles was 4 (1–16). PS 0 (58%) and PS 1 (42%). No patient had COVID-19.No COVID cohort’ (NCC): 20 patients, 15 (75%) men, mean 67 years (54–85). Cancer stage: stage IV (75%), IIIB (25%). All patients had received lines previously and none had received immunotherapy. Median medical visits was 7 (3–11) with no telephone consults. Median number of cycles was 3 (1–11). PS 0 (70%) and PS1–2 (30%). The rest of the variables are shown in table 1.Abstract 4CPS-296 Table 1 CC (%) NCC (%) RAR 30% (95% CI ) p value Worsening PS 30 0 15.8 to 44.2 <0.05Therapeutic rest break 35 0 20.2 to 49.7 <0.05 Delays 100 30 −90.1 to −49.9 <0.05 Respiratory infections 10 15 −13.2 to 23.2 >0.05 Disease progression 30 45 −11.2 to 41.2 >0.05 Deaths 18 25 −14.8 to 29.8 >0.05 Conclusion and relevanceIn spite of the limitations of the study, the new strategies of clinical management during the COVID-19 pandemic (telephone consults and therapeutic tire) did not appear to affect disease progression and NSCLC patient survival although worsening of performance status was observed.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and ImportanceNine drugs are currently approved for the treatment of ankylosing spondylitis (AS) in adults: adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, ixekizumab, ...secukinumab, upadacitinib and tofacitinib. Tofacitinib was the last of them to receive its approval. However, there are no direct comparisons between them.Aim and ObjectivesTo establish whether the drugs approved for AS in adults can be considered equivalent therapeutic alternatives (ATE) in efficacy in AS.Material and MethodsA search of clinical trials of these drugs in adult patients with AS was conducted, phase II or III, double-blinded, controlled with another drug or placebo.Other inclusion criteria wereEndpoint: ASAS40 (a ≥40% improvement and an absolute improvement from baseline of the Assessment in SpondyloArthritis International Society).Follow-up time: 12-16 weeks.For those drugs with more than one study, a previous meta-analysis was performed using Joaquin Primo calculator. An adjusted indirect comparison (IC) of the drugs used in AS versus tofacitinib was performed using the Bucher method, using Joaquin Primo calculator. Due to lack of data in the literature and considering that therapy failure can be recovered with second lines, half of the ASAS40 value obtained in meta-analysis was taken as delta value. ATE guide was followed in order to establish a positioning.ResultsSixteen studies were included4 adalimumab, 2 golimumab, 1 infliximab, 1 certolizumab, 2 etanercept, 1 upadacitinib, 2 tofacitinib, 1 secukinumab and 2 ixekizumab. The difference in ASAS40 of the drugs before versus tofacitinib expressed as RAR (IC 95%) was: Adalimumab 4 (-6,1; 14,1), certolizumab -7,3 (-25,1; 10,5), etanercept 2 (-11,5; 15,5), golimumab -5 (-16,3; 6,3), infliximab 8,43 (-4,8; 21,6), ixekizumab -9 (-20, 6; 2,6), secukinumab -2,7 (-18,3; 12,9), upadacitinib -1,9 (-17,8; 13,9). Adalimumab, etanercept and tofacitinib are considered ATE. Infliximab, upadacitinib, secukinumab, golimumab, certolizumab, ixekizumab and tofacitinib can also be considered ATE, being the probability of clinically relevant difference <50% (most of the 95% CI is in the equivalence range) and the failure does not involve serious/irreversible damage.Conclusion and RelevanceTofacitinib and the rest of these drugs could be considered ATE. For a definitive statement, the criteria of safety and adequacy should be considered.References and/or AcknowledgementsConflict of InterestNo conflict of interest
Background and importanceA combination of daratumumab, bortezomib, melphalan and prednisone with daratumumab for maintenance (DVMP-D) has been authorised as a firstline treatment for patients with ...newly diagnosed multiple myeloma who are ineligible for stem cell transplantation (NDMM-NoT). An economic comparison of different alternatives available was performed, according to their economic impact.Aim and objectivesTo develop an economic comparison among the therapeutic alternatives in NDMM.Material and methodsA bibliographic research was conducted in MEDLINE and EMBASE databases to identify treatment schemes with daratumumab, lenalidomide, bortezomib and thalidomide, or their combinations, in NDMM. Only authorised treatments used in clinical practice were selected. Efficacy was assessed as progression free survival. Randomised clinical phase II–III trials, which compared selected therapeutic alternatives in patients with NDMM-NoT, were included. Articles in Spanish or English language were selected. Costs of the first year of treatment were calculated from a National Health System perspective, using notified laboratory sale prices and including taxes (4% VAT) and a 7.5% rebate (in accordance with the national Royal Decree Law 8/2010). Associated direct costs in the first year were added. Incremental costs of each therapeutic alternative with respect to the reference was quantified. DVMP-D was taken as the reference in the cost incremental study.ResultsResults of the systematic review included 593 studies. Nine trials were selected which analysed seven drug combinations: DVMP-D; bortezomib+melphalan+prednisone (VMP); melphalan+prednisone+thalidomide with thalidomide for maintenance (MPT-T); lenalidomide+dexamethasone for maintenance (RD); lenalidomide+dexamethasone for 18 cycles (RD18); melphalan+thalidomide+prednisone (MTP); and bortezomib+lenalidomide+dexamethasone with lenalidomide+dexamethasone for maintenance (VRD-RD). Daratumumab+lenalidomide+dexamethasone with daratumumab for maintenance was excluded for non-use by the National Health System (combination not funded). A visit to outpatients was estimated at 167€, according to the bibliography. Treatment costs for the first year were: DVMP-D 184 214€; VMP 44 435€; MPT-T 44 435€; RD 81 520€; RD18 81 520€; MTP 77 209€; and VRD-RD 104 850€. Regarding incremental costs, the most expensive scheme was the reference treatment (DVMP-D), followed by VRD-RD (−79 364€). The cheapest combination was MPT-T (−164 094€), followed by VMP (−139 779€).Conclusion and relevanceThere are seven treatments, including daratumumab, lenalidomide, bortezomib and thalidomide for NDMM-NoT. The most expensive schemes for the first year of treatment are DVMP-D and VRD-RD; and the cheapest combinations are MPT-T and VMP.References and/or acknowledgementsNone.No conflict of interest.
Background and importanceErenumab, fremanezumab, galcanezumab and eptinezumab are monoclonal antibodies targeting the calcitonin gene related peptide pathway (anti-CGRP), used as preventive treatment ...in chronic migraine (CM).Aim and objectivesTo evaluate whether anti-CGRP drugs are equivalent therapeutic alternatives (ETA) in CM through an adjusted indirect treatment comparison (ITC).Material and methodsA bibliographic search of randomised clinical trials (RCTs) in Pubmed was performed (20 May 2019). Inclusion criteria: phase II/III RCTs of anti-CGPR with similar populations, follow-up duration and comparator treatments. CM was defined as ≥15 headache days/month, of which ≥8 were migraine days (event duration ≥4 hours). Exclusion criteria: RCTs with different clinical CM context and other CM definitions. Efficacy end point was ≥50% reduction in migraine days/month (measured from the beginning of treatment to 12 weeks). An ITC was developed using Bucher’s method. Delta value (Δ, maximum difference as a clinical criterion of equivalence) was calculated according to the ETA guide1: use was made of half of the absolute risk reduction (ARR) obtained in the meta-analysis of RCTs included in the ITC (pooled ARR=20%; Δ=10%).ResultsSix clinical trials were founderenumab (n=3), fremanezumab (n=2), glacanezumab (n=1) and eptinezumab (n=0). One study of erenumab2 and another of fremanezumab3 were selected. The rest were not included in the ITC (non-compliance with the inclusion criteria). Trials included were three arm (control and two different drug regimens), double blind, placebo controlled RCTs. Results of the ITC are shown in table 1. Abstract 4CPS-132 Table 1 Reduction of ≥ 50% migraine days/month (ARR (95% CI)) Erenumab 70 mg Erenumab 140 mg Fremanezumab quarterly 3 (−7.56 to 13.56) 2 (−8.64 to 12.64) Fremanezumab monthly 6 (−4.59 to 16.59) 5 (−5.66 to 15.66) In all cases, there were no statistically significant differences; most 95% CI values were within the calculated delta margins.Conclusion and relevanceITC showed no statistically significant differences in ≥50% reduction in migraine days/month between erenumab and fremanezumab. Probable clinical equivalence was found between erenumab and fremanezumab. These drugs could be considered ETA in CM. Further studies are necessary to include galcanezumab and eptinezumab in the ITC.References and/or acknowledgements1. Alegre-del-Rey EJ, et al. Evaluación y posicionamiento de medicamentos como alternativas terapéuticas equivalentes. Med Clin 2014;143:85–90.2. Tepper S, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017;16:425–434.3. Silberstein SD, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med 2017;377:2113–2122.No conflict of interest.
Background and importancePembrolizumab monotherapy (Pb) showed benefit in terms of overall survival (OS) and progression free survival (PFS) compared with chemotherapy alone (CT) in untreated ...metastatic non-small cell lung cancer (mNSCLC) with PD-L1 ≥50% expression. The Pb-CT combination presented benefit in terms of OS and PFS in untreated metastatic squamous NSCLC (mSNSCLC), regardless of PD-L1 expression. No randomised clinical trials (RCTs) of Pb-CT versus Pb alone have been done.Aim and objectivesTo assess the comparative efficacy of Pb and Pb-CT in untreated mSNSCLC patients with PD-L1 ≥50% using an adjusted indirect treatment comparison (ITC).Material and methodsA bibliographic search was conducted in the Pubmed database (2 October 2019). Inclusion criteria were phase III RCTs, Pb and Pb-CT treatments, similar mSNSCLC population (with PD-L1 ≥50%), follow-up period and end points(OS or PFS). Exclusion criteria were mSNSCLC population with EGFR or ALK mutations. An ITC was developed using Bucher’s method. Delta value (Δ), maximum acceptable difference as a clinical criterion of no inferiority, was set at 0.70 (and its inverse, 1.43), used to calculate the sample size in the Pb-CT trial. The Shakespeare method was used to estimate the probability of the results out of the Δ margins.ResultsTwo studies, one for each regimen,1 2 were found in the literature search. Limitations found between Pb-CT and Pb trials included populations (all patients vs only patients with PD-L1 ≥50%, respectively, subgroup data used for ITC) and small size of the squamous subgroup. No OS data were available for the squamous subgroup in the Pb trial. PFS was taken as the primary end point for ITC. Results of RCTs and ITC are shown in table 1.Abstract 4CPS-076 Table 1Reference PFS Pb-CT vs CT1 HR=0.37 (95% CI 0.24–0.58, PD-L1 ≥50% subgroup) Pb vs CT2 HR=0.35 (95% CI 0.17–0.71, squamous subgroup) Pb-CT vs Pb (ITC) HR=1.06 (95% CI 0.46–2.45) No significant differences in PFS between Pb-CT and Pb were found. The 95% CI exceeded Δ on both sides (high level of uncertainty). The probability of a result out of Δ were 24.14% below and 16.54% above.Conclusion and relevanceITC did not show significant differences in PFS between Pb-CT and Pb. No evidence of clinically relevant benefit from one or other regimen was found. Considering the toxicity related to the addition of CT, Pb monotherapy would be preferable in untreated mSNSCLC with PD-L1 ≥50%.References and/or acknowledgements1. Paz-Ares L, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 2018;379:2040–2051.2. Reck M, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823–1833.No conflict of interest.
Background and importanceAccording to the PARAMOUNT trial, induction chemotherapy with a platin/pemetrexed combination and pemetrexed maintenance therapy reduced the risk of progression free survival ...(PFS) and overall survival (OS) in patients with non-cell lung cancer (NSCLC).Aim and objectivesThe aim of the study was to assess the effectiveness and safety of this drug combination in NSCLC and to evaluate the degree of agreement with the PARAMOUNT results.Material and methodsA descriptive retrospective study was conducted. All patients that initiated treatment with platin/pemetrexed from January 2018 to September 2019 were included. Clinical data were obtained from digital clinical history and the prescription software Farmis Oncofarm: sex, age, stage, performance status (PS), periodicity of chemotherapy, dose received and number of cycles. PFS and OS were used as efficacy end points, and were obtained by the Kaplan–Meier method (SPSS Statistics programme).In terms of safety, adverse events (AE) of any grade were recorded for assessment of the safety profile. Effectiveness data and safety were compared with the PARAMOUNT results.ResultsForty-two patients were enrolled, 36 men and 6 women, with an average age of 67 years (range 42–80). Cancer stage was as follows: stage IV (90%), stage IIB (7%) and stage IIIA (3%). Baseline PS was 0–1 in 60% of cases and in the remainder, 2–3. All patients received as induction therapy on day 1, 21 day cycles of pemetrexed (500 mg/m2) in combination with cisplatin 75 mg/m2 (n=16) or carboplatin AUC=5 (n=26). Pemetrexed maintenance therapy (500 mg/m2) was administrated until progression or death. The median number of cycles was 4 (1–16). Median PFS was 4 months (95% CI 3 to 5) and median OS was 17 months (95% CI 11 to 21). In the PARAMOUNT study, median PFS was 4 months and median OS was 14 months. Sixty per cent of patients (n=25) had AE. The most common AE were mucositis (n=7), asthenia (n=6), diarrhoea (n=3), dermatitis (n=3), vomiting (n=3), anaemia (n=2) and neutropenia (n=2). In the clinical trial, the most common AE of any grade were anaemia, neutropenia, fatigue and nausea.Conclusion and relevancePFS and OS showed a clinical benefit. The safety profile for the use of this combination showed it was tolerated. The effectiveness and AE were similar compared with the published clinical trial.References and/or acknowledgementsNo conflict of interest.
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