This study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an ...efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015-2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75-1.55), and HR 0.91 (95% CI 0.74-1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07-2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background Endoscopic resection (ER) is an important treatment for high-grade intraepithelial neoplasia and early cancer in Barrett's esophagus. ER-cap requires submucosal lifting and positioning of ...a snare in the cap, making it technically demanding and laborious. Multiband mucosectomy (MBM) uses a modified variceal band ligator and requires no submucosal lifting or positioning of a snare. Objective To compare ER-cap and MBM for piecemeal ER of early Barrett's neoplasia. Design Randomized, controlled trial. Setting Tertiary-care and community-care centers. Patients This study involved 84 patients (64 men; median age 70 years) undergoing piecemeal ER of Barrett's neoplasia. Intervention Piecemeal ER was performed by using ER-cap (n = 42) or MBM (n = 42). Main Outcome Measurements Safety, efficacy, procedure time, costs. Results Procedure time (34 vs 50 minutes; P = .02) and costs (€240 vs €322; P < .01) were significantly less with MBM compared with ER-cap. MBM resulted in smaller resection specimens than ER-cap (18 ×13 mm vs 20 × 15 mm; P < .01). Maximum thicknesses of specimens and resected submucosa were not significantly different. There were no clinically relevant bleeding episodes. Four perforations occurred, 3 with ER-cap, 1 with MBM ( P = not significant). Limitations Potential bias because of different levels of experience among participating endoscopists. Conclusion Piecemeal ER with MBM is faster and cheaper than with ER-cap. Despite the lack of submucosal lifting, MBM appears not to be associated with more perforations. Although MBM results in slightly smaller specimens, the clinical relevance of this may be limited because depth of resections does not differ between both techniques. MBM may thus be preferred for piecemeal ER of early Barrett's neoplasia. (Clinical trial registration number: NTR1435.)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The divergence between clinical trial results and real-world outcomes is largely unknown for many cancer types. The present study aims overall to assess the efficacy-effectiveness gap (difference ...between outcomes in clinical trials and the real world) in systemic treatment for metastatic nonsmall cell lung cancer (NSCLC).All patients diagnosed with stage IV NSCLC between 2008 and 2014 within a network of seven Dutch large teaching hospitals (Santeon) were studied. For every patient, an efficacy-effectiveness (EE) factor was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment.From 2989 diagnosed patients, 1214 (41%) started with first-line treatment. For all studied regimens, real-world OS was shorter than OS reported in clinical trials. Overall, the EE factor was 0.77 (95% CI 0.70-0.85; p<0.001). Real-world patients completed their treatment plan less often and proceeded less frequently to further lines of treatment. These parameters together with Eastern Cooperative Oncology Group performance status explained 35% of the variation in EE factor.Survival of patients with metastatic NSCLC treated with chemotherapy or targeted therapy in real-world practice is nearly one-quarter shorter than for patients included in trials. Patients' performance status, earlier discontinuation and fewer subsequent lines of treatment partly explained this difference.
Treatment options for advanced non-small cell lung cancer (NSCLC) include immunotherapy. Elevated carcinoembryonic antigen (CEA) and cancer antigen 125 (Ca-125) levels are associated with poorer ...prognoses of resected NSCLC, but currently no predictive biomarkers exist for immunotherapy response. This study evaluated CEA and Ca-125 as predictive biomarkers for immunotherapy efficiency in patients with metastatic NSCLC.
The single-centre observational retrospective study includes NSCLC stage III/IV patients treated with programmed death-ligand 1 (PD-L1) inhibitors nivolumab or pembrolizumab. The primary study endpoint was treatment response assessed by CT-scan following RECIST-criteria 1.1. CEA/Ca-125 serum values were determined at initiation of treatment and repeated every 2 weeks. Values closest to the day of CT-scan were compared to baseline values.
A total of 136 patients were treated with mono-immunotherapy. Of these, 73 patients were included in the CEA group and 53 patients were included in the Ca-125 group. Baseline CEA and Ca-125 ranged from 8.14 to 5,909 and 1.1 to 4,238 respectively. The sensitivity for Ca-125 as predictor for tumor response was 62.9% (95% CI=61.8%-63.6%), specificity 61.1% (95% CI=60.2%-62.0%), with a positive predictive value (PPV) of 75.9% (95% CI=75.2%-76.7%). For CEA, the sensitivity was 72.0% (95% CI=71.5%-72.5%), specificity 47.1% (95% CI 46.4%-47.8%), with a PPV of 80.0% (95% CI=79.6%-80.4%).
Increased serum CEA might predict tumor progression in NSCLC patients treated with PD-L1 inhibitors. Unconfirmed progression accompanied by increased CEA would support discontinuation of the immunotherapy, while continuation would be advised when serum CEA is not increased.
Introduction
Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis. Effectiveness of MTX has large inter-patient variability and at present ...therapeutic drug monitoring (TDM) of MTX is not possible. Upon administration, MTX is actively transported into cells and metabolized to its active forms by adding glutamate residues forming MTXPG
(n=1–5)
resulting in enhanced cellular retention. In this study we address the question whether different MTXPG
(n)
concentrations in red blood cells (RBC) of patients with sarcoidosis after 3 months of MTX therapy correlate with response to treatment.
Methods
We retrospectively included patients with sarcoidosis that had started on MTX therapy and from whom blood samples and FDG-PET/CT were available 3 and 6–12 months after MTX initiation, respectively. FDG-uptake was measured by SUVmax in the heart, lungs and thoracic lymph nodes. Changes in SUVmax was used to determine anti-inflammatory response after 6–12 months of MTX therapy. MTXPG
(n)
concentrations were measured from whole blood RBC using an LC–MS/MS method. Pearson correlation coefficients were calculated to evaluate the relationship between changes in the SUVmax and MTXPG
(n)
concentrations.
Results
We included 42 sarcoidosis patients treated with MTX (15 mg/week); 31 with cardiac sarcoidosis and 11 with pulmonary sarcoidosis. In MTXPG
3
and MTXPG
4
a significant negative relation between the absolute changes in SUVmax and MTXPG
(n)
was found r = − 0.312 (n = 42, p = 0.047) for MTXPG
3
and r = − 0.336 (n = 42, p = 0.031 for MTXPG
4
). The other MTXPG
(n)
did not correlate to changes in SUVmax.
Conclusion
These results suggest a relation between MTXPG
(n)
concentrations and the anti-inflammatory effect in patients with sarcoidosis. Further prospective validation is warranted, but if measuring MTXPG concentrations could predict treatment effect of MTX this would be a step in the direction of personalized medicine.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PURPOSE OF REVIEWWith the development of targeted therapies, the treatment strategy of patients with advanced or metastatic non-small cell lung cancer (NSCLC) has changed tremendously. In this ...review, we focus on the different aspects of the treatment of oncogene-driven NSCLC.
RECENT FINDINGSPatients with an EGFR or ALK alteration show a better clinical outcome with tyrosine kinase inhibitor (TKI) treatment compared to chemotherapy.Patients with a ROS1 rearrangement or a BRAF V600E mutation show favorable clinical outcome with TKI treatment compared to chemotherapy, although randomized trials are not available.Patients on TKIs will eventually develop disease progression because of acquired resistance.The treatment with immunotherapy in EGFR and ALK-positive NSCLC patients did not improve overall survival over that of chemotherapy.Blood-based genetic analysis provides the opportunity to noninvasively screen patients for the presence of oncogenic drivers and to monitor resistance during TKI treatment.
SUMMARYTargeted molecular therapies are now standard of care for patients with oncogene-driven NSCLC with a good clinical benefit and minimal toxicity. The role of immunotherapy in patients with molecular alterations is still unclear. Blood-based genotyping has gained interest in the diagnostic and resistance monitoring setting for patients with NSCLC.
This retrospective study was performed to evaluate real-world oncological outcomes of patients treated with chemo-based therapy for muscle-invasive or metastatic bladder cancer (MIBC/mBC) and compare ...results to data from RCTs and other cohorts. Among 1578 patients diagnosed, 470 (30%) had MIBC/mBC. Median overall survival (mOS) for RC alone (47 months), first-line (13 months) and second-line (7 months) chemotherapy, and chemotherapy for recurrent disease (8 months) were similar to literature. Treatment with neoadjuvant and induction chemotherapy (NAIC) was only utilized in 9% of patients, and often in patients with poor disease status, resulting in a lower mOS compared to literature (35 and 20 months, respectively). Patients treated with chemotherapy had many adversities to treatment, with only 50%, 13%, 18% and 7% of patients in NAIC, first-line, salvage after RC, and second-line setting completing the full pre-planned chemotherapy treatment. Real-world data shows NAIC before RC is underutilized. Adversities during chemotherapy treatment are frequent, with many patients requiring dose reduction or early treatment termination, resulting in poor treatment response. Although treatment efficacy between RCTs and real-world patients is quite similar, there are large differences in baseline characteristics and treatment patterns. Possibly, results from retrospective studies on real-world data can deliver missing evidence on efficacy of chemotherapy treatment on older and 'unfit' patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•A detailed analysis of the systemic palliative treatment of NSCLC in the Netherlands.•48% of patients received 1st line systemic treatment, 34% of those 2nd line.•Patients with a poor PS were more ...likely to discontinue treatment early.•Large interhospital differences were found for utilization of systemic treatment.•No apparent change in overall survival was found during the time of study.
The present study aims to give a detailed overview of day-to-day practice in the systemic treatment of NSCLC stage IIIB/IV and its clinical outcomes in six large teaching hospitals in the Netherlands in the period 2008–2012.
A retrospective observational cohort study was conducted in the Care for Outcome registry. Patients diagnosed with stage IIIB/IV NSCLC were included and drug data were collected. Outcomes included percentage of patients treated with systemic treatment, percentage of different first line treatment options, survival, and number and percentage of switches, dose reductions (<80% of the initial dose), and early discontinuation (<4 cycles). Descriptive analyses were conducted per hospital, year of diagnosis and several patient characteristics. Predictors for early discontinuation were explored in a logistic regression model.
Overall, 47,9% of 2158 patients that were included received systemic treatment and 33,7% of those received second line treatment. Treatment frequencies were different between age categories, disease stage, PS and hospital (p<0.001). Half of the patients received <4 cycles and dose reductions were found for 20% of all patients. Interhospital differences were observed for early discontinuation and the number of switches. PS2-3 was associated with early discontinuation (OR 1.97 (p=0,007). Median survival was not different between hospitals and years of diagnosis.
We provided detailed overview of day-to-day systemic treatment of NSCLC for six hospitals that (a) can fuel interhospital discussion to streamline treatment towards best practice and (b) can serve as reference data for follow-up of the adoption of novel systemic treatment options for advanced lung cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Purpose
The aim of this study is to assess how clinical outcomes in real‐world (effectiveness) correspond to the outcomes in clinical trials (efficacy) of systemic treatments for extensive disease ...small cell lung cancer (ED SCLC).
Methods
All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were identified and followed‐up from date of diagnosis until death or end of data collection. For every patient, an efficacy‐effectiveness factor (EE factor) was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment.
Results
From 792 diagnosed patients, 568 (72%) started with first‐line treatment. Overall, the median EE factor was 0.79 (P < .001 from 1.00). Poor performance status (ECOG≥2) and a higher age at diagnosis (age ≥ 65 years) were independent predictors for a lower EE factor. The EE gap was 43% in patients with both age ≥ 65 years and ECOG ≥2 (EE factor 0.57). The mean age and the proportion of patients with ECOG≥2 in real‐world were different from those in clinical trials (mean age of 66 versus 62 years, and ECOG≥2 25% versus 17%; both P < .001).
Conclusion
OS of patients with ED SCLC treated with systemic therapy in real‐world practice is 21% shorter than for patients included in trials. Age at diagnosis and performance status partly explain this gap.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The effect of switching from originator infliximab to biosimilar infliximab in patients with sarcoidosis is unknown. The objective of this study is to investigate the effect of switching from ...Remicade
or Inflectra
to Flixabi
in patients with severe refractory sarcoidosis. This single center retrospective cohort study was performed at St Antonius Hospital Nieuwegein, The Netherlands. All patients diagnosed with severe refractory sarcoidosis receiving Remicade
or Inflectra
switched to Flixabi
. The primary outcome was infliximab discontinuation within 6 months of switching. Secondary endpoints included adverse events and loss of clinical, functional, or inflammatory response. Out of 86 patients who switched to Flixabi
, 79 patients had complete data. None of the 79 patients discontinued infliximab during the first 6 months after switching. Five patients reported an adverse event related to Flixabi
treatment. We found no change from baseline in FVC, FEV1, DLCOc, 6MWT, and infliximab trough levels 26 weeks after switching. An improvement in physical functioning of 7.3 ± 13.4 points (
= 0.002) with RAND/SF36 and in biomarker sIL-2R (-475.58 ± 1452.39;
= 0.005) was observed. Switching from originator infliximab Remicade
or biosimilar infliximab Inflectra
to biosimilar infliximab Flixabi
did not result in treatment discontinuation or loss of clinical/functional/inflammatory remission.
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