ml-RECIST: Machine learning to estimate RECIST in patients with NSCLC treated with PD-(L)1 blockade.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9052-9052
Author(s):  
Kathryn Cecilia Arbour ◽  
Luu Anh Tuan ◽  
Hira Rizvi ◽  
Adam Yala ◽  
Matthew David Hellmann ◽  
...  
Keyword(s):  
Machine Learning ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Radiology Reports ◽  
Clinical Databases ◽  
Real World Evidence ◽  
Standard Of Care Treatment ◽  
Similar Accuracy ◽  
Effective Use

9052 Background: Real-world evidence (RWE) is increasingly important for discovery and may be an opportunity for regulatory approval. Effective use of RWE relies on determining treatment-specific outcomes, such as overall response rate (ORR) and progression-free survival (PFS), which are challenging to accurately evaluate retrospectively and at scale. We hypothesized the use of machine learning of text radiology reports from patients with NSCLC treated with PD-1 blockade could be used to train a model that estimates RECIST-defined outcomes. Methods: 2753 imaging reports from 453 patients with advanced NSCLC treated with PD-1 blockade were collected and separated into independent training (80%, n = 362) and validation (20%, n = 92) cohorts. Reports were limited to interval of PD-1 blockade. RECIST reads performed by thoracic radiologists on all patients served as “gold standard” to determine ORR, occurrence of, and date of progression. Baseline reports were compared to all follow up reports to determine machine-learning RECIST (ml-RECIST). A four layers neural-network model for classification was proposed to solve the three above tasks. Results: In the training cohort, ml-RECIST best estimated ORR by RECIST (accuracy CR/PR 84%, SD 82%, POD 91%). ml-RECIST estimated PFS by RECIST accurately predicting progression occurred at any time (86%) and exact progression date (65%). Date of progression was closely correlated (Pearson’s r coefficient = 0.91, 95% CI:0.89-0.94, p < 0.001) in patients determined to have progressed by both methods. Similar accuracy of ml-RECIST was observed in the validation cohort (accuracy CR/PR 84%, SD 80%, POD 90%; progression occurred 86%, progression date 72%). Accuracy was consistent when RECIST reads were performed prospectively as part of clinical trials vs retrospectively for standard of care treatment (e.g. CR/PR 82% vs 88%, respectively). ml-RECIST-defined response similarly determined improvement in overall survival compared to RECIST (HR = 0.19, p < 0.001 vs HR = 0.26, p < 0.001 respectively). Conclusions: Machine learning-RECIST ("ml-RECIST") accurately estimates outcomes using imaging text reports. ml-RECIST may be tool to determine outcomes expeditiously and at scale for use in RWE studies, enabling more useful and reliable applications of large clinical databases.

scholarly journals National Bariatric Surgery Registries: an International Comparison

2021 ◽  
Author(s):  
Erman O. Akpinar ◽  
Perla J. Marang- van de Mheen ◽  
Simon W. Nienhuijs ◽  
Jan Willem M. Greve ◽  
Ronald S. L. Liem
Keyword(s):  
Standard Of Care ◽  
Population Based ◽  
Substantial Agreement ◽  
Perfect Agreement ◽  
Moderate Agreement ◽  
Real World Evidence ◽  
International Collaborations ◽  
Global Registry ◽  
Registry Report

Abstract Introduction Pooling population-based data from all national bariatric registries may provide international real-world evidence for outcomes that will help establish a universal standard of care, provided that the same variables and definitions are used. Therefore, this study aims to assess the concordance of variables across national registries to identify which outcomes can be used for international collaborations. Methods All 18 countries with a national bariatric registry who contributed to The International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) Global Registry report 2019 were requested to share their data dictionary by email. The primary outcome was the percentage of perfect agreement for variables by domain: patient, prior bariatric history, screening, operation, complication, and follow-up. Perfect agreement was defined as 100% concordance, meaning that the variable was registered with the same definition across all registries. Secondary outcomes were defined as variables having “substantial agreement” (75–99.9%) and “moderate agreement” (50–74.9%) across registries. Results Eleven registries responded and had a total of 2585 recorded variables that were grouped into 250 variables measuring the same concept. A total of 25 (10%) variables have a perfect agreement across all domains: 3 (18.75%) for the patient domain, 0 (0.0%) for prior bariatric history, 5 (8.2%) for screening, 6 (11.8%) for operation, 5 (8.8%) for complications, and 6 (11.8%) for follow-up. Furthermore, 28 (11.2%) variables have substantial agreement and 59 (23.6%) variables have moderate agreement across registries. Conclusion There is limited uniform agreement in variables across national bariatric registries. Further alignment and uniformity in collected variables are required to enable future international collaborations and comparison. Graphical abstract

scholarly journals A novel predictor of clinical progression in patients on active surveillance for prostate cancer

2019 ◽  
Vol 13 (8) ◽  
Author(s):  
Guan Hee Tan ◽  
Antonio Finelli ◽  
Ardalan Ahmad ◽  
Marian Wettstein ◽  
Alexandre Zlotta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Roc Curves ◽  
Standard Of Care ◽  
Low Risk ◽  
Clinical Progression

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP).     Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years follow-up. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo / prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival curves between TCLo density groups. Test characteristics of TCLo were explored with receiver operating characteristic (ROC) curves.     Results: We included 181 patients who had CBx between 2012-2015, and met inclusion criteria. The mean age of patients was 62.58 years (SD=7.13) and median follow-up was 60.9 months (IQR=23.4). A high TCLo density score (>0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p<0.001), and GP (HR 3.85, 95% CI: 1.91-7.73, p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression.     Conclusion: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PC.

P14.90 Survival outcomes and prognostic factors in glioblastoma patients treated with radiotherapy plus concomitant and adjuvant temozolomide - real-world study

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii55-ii55
Author(s):  
M J Sousa ◽  
J Magalhães ◽  
R Basto ◽  
C Costa ◽  
A Pego ◽  
...  
Keyword(s):  
Survival Rate ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Survival Outcomes ◽  
Hematologic Toxicity ◽  
Current Standard ◽  
Adjuvant Temozolomide ◽  
Standard Of Care Treatment ◽  
Ecog Ps

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). This study aimed to evaluate the survival outcomes and identify predictors of survival among these patients. MATERIAL AND METHODS We performed a single-centre retrospective analysis of GBM patients treated with radiotherapy plus concomitant and adjuvant TMZ from 2013 to 2020. The analyses of progression-free survival (PFS) and overall survival (OS), each one evaluated starting from initial diagnosis, were performed. Survival curves were estimated with the Kaplan- Meier method and compared using the log-rank test. RESULTS Fifty-eight patients were identified. The median age was 61 years (range 18- 80), 51 (88%) patients were in ECOG-PS 0–1, 6 (10%) patients had isocitrate dehydrogenase (IDH) mutation and 53 (91%) of patients had undergone debulking surgery. At a median follow-up of 21 months, median OS was 12.8 months (95% confidence interval [CI] 9.7–15.9), whereas median PFS was 9.5 months (95% CI 8.5–10.5). The 1-year survival rate was 42% and the 2-year survival rate was 10%. Grade 3 or 4 hematologic toxicity occurred in 11 (19%) patients. Twenty-five (42%) patients completed at least 6 cycles of TMZ monotherapy with statistically significant differences between this sub-group and those who weren’t able to continue TMZ monotherapy [median OS 19.3 months (95% CI 14.4–24.2) vs 10.6 months (95% CI 7.8–13.4) p&lt;0.001]. ECOG-PS = 0 [median OS 16.7 months (95% CI 13.4–20.0, p=0.001)] and patients under 65 years of age [median OS 15.6 months (95% CI 12.3–18.9, p=0.02) were associated with significantly better median OS. CONCLUSION The current standard of care treatment for GBM remains poor. An important factor predictor of survival is the completion of the 6 maintenance cycles of TMZ. At baseline, ECOG PS and the patient’s age could be used to define patient prognosis.

scholarly journals NIMG-07. LACUNARITY AND FRACTAL DIMENSION ACT AS PRETREATMENT IMAGING BIOMARKERS FOR SURVIVAL IN GLIOBLASTOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi162-vi163
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Haylye White ◽  
Maciej Mrugala ◽  
Leland Hu ◽  
...  
Keyword(s):  
Fractal Dimension ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Imaging Biomarkers ◽  
Free Survival ◽  
Patient Cohort ◽  
Biological Phenomena ◽  
Microenvironmental Factors ◽  
Standard Of Care Treatment

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of only 15 months with standard of care treatment. Lacunarity, a quantitative morphological measure of how shapes fill space, and fractal dimension, another morphological measure of the complexity of pixel arrangement, of segmented necrotic regions on gadolinium-enhanced T1 weighted (T1gd) MRI have previously been shown to distinguish both overall survival (OS) and progression free survival (PFS) in GBM (n = 95). In our larger patient cohort (n = 389), we sought to validate or refute previously published results connecting morphological metrics and patient survival. We identified pretreatment necrotic regions of our retrospective first-diagnosis GBM patient cohort using segmented T1gd MRI enhancing regions. We calculated lacunarity and fractal dimension across all T1gd MRI slices with enhancing tumor, and used the median lacunarity and fractal dimension values for our analysis. We find that a lacunarity threshold can significantly distinguish OS (14 months vs 19 months median, log-rank p = 0.015, n = 389) and a fractal dimension threshold can significantly distinguish PFS (8 months vs 11 months median, log-rank p = 0.015, n = 123). We believe that morphological metrics such as lacunarity and fractal dimension could play a role in standard-of-care prognostic considerations at tumor presentation. This link between morphological and survival metrics could be driven by underlying biological phenomena or microenvironmental factors that should be further explored.

scholarly journals Comparison of Phase 3 Ibrutinib Results Versus Standard of Care in Sweden in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1751-1751 ◽  
Author(s):  
Anders Österborg ◽  
Anna Asklid ◽  
Joris Diels ◽  
Johanna Repits ◽  
Frans Söltoft ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Phase 3 ◽  
Free Survival ◽  
Line Of Therapy

Abstract Background Ibrutinib (Ibr), an oral, first-in-class covalent Bruton's tyrosine kinase inhibitor, showed in the Phase 3 RESONATE trial significantly improved progression-free survival (PFS, hazard ratio [HR] =0.22, p<0.001) and overall survival (OS, HR=0.39,p=0.001) compared with ofatumumab (ofa) in patients with previously treated CLL who were not eligible for chemoimmunotherapy (Byrd et al, NEJM 2013). Long-term follow-up data from a single arm Phase 2 study have also demonstrated that patients treated with ibrutinib have long durable responses with a PFS at 2.5 years of 69% (Byrd et al, Blood 2015). While ofatumumab is a licensed comparator and included in treatment guidelines, some Health Technology Assessment (HTA) bodies require comparisons with a wider range of treatments. In the absence of direct head-to-head comparison of single-agent ibrutinib with other frequently used treatments in this patient population, additional comparative evidence against standard of care as observed in clinical practice can provide useful insights on the relative efficacy of ibrutinib. Naïve (unadjusted) comparisons of outcomes from different sources are prone to bias due to confounding, as treatment assignments were not randomly assigned, and populations can vary in important prognostic factors. The objective of this analysis was to compare the relative efficacy of Ibr versus physician's choice in R/R CLL-patients based on patient-level data from RESONATE pooled with an observational cohort, adjusting for confounders using multivariate statistical modelling. Methods Patient-level data from the Phase 3 RESONATE trial (Ibr: n=195; ofa: n=196) were pooled with data from a retrospective observational study conducted in the Stockholm area in Sweden. This retrospective study collected efficacy and safety data from a detailed, in-depth retrospective review of individual patient files from 148 consecutively identified patients with R/R CLL initiated on second or later line treatment between 2002 and 2013 at the four CLL-treating centers in Stockholm, Sweden, with complete follow-up. Longitudinal follow-up in subsequent treatment lines was available for patients in 3rd (n=91), 4th (n=51), 5th (n=29), and 6+ (n=15) line, and as such individual patients could contribute information to the analysis for multiple lines of therapy, with baseline defined as the date of initiation of the actual treatment line. A multivariate cox proportional hazards model was developed to compare PFS and OS between treatments, including line of therapy, age, gender, Binet stage, ECOG, and refractory disease as covariates. Adjusted HRs and 95% CIs are presented vs. Ibr. Results Across all treatment lines, fludarabine-cyclophosphamide (FC) (n=64), chlorambucil (n=59), alemtuzumab (n=33), FC+rituximab (FCR) (n=30), bendamustine+rituximab (BR) (n=28), and other rituximab-based combination chemotherapy (n=28) were the most frequently used treatments. Line of therapy, age and gender, Binet stage, ECOG performance status, and refractory disease were all independent risk factors for worse outcome on both PFS and OS. The adjusted HR for PFS and OS pooled observational data versus Ibr were 6.80 [4.72;9.80] (p<0.0001) and 2.90 [1.80;4.69] (p<0.0001). HR's for PFS/OS versus most frequent treatment regimens ranged between 2.50/1.82 (FCR) and 14.00/5.34 (anti-CD20 Mab). Baseline adjusted results for the Ofa-arm in RESONATE were comparable for both PFS and OS to outcome data from the consecutive historical cohort, however OS outcomes for Ofa were partly confounded by cross-over to Ibr. Conclusions Comparison of results from the Phase 3 RESONATE study with treatments used as part of previous standard of care in a well-defined cohort of consecutive Swedish patients shows that ibrutinib is superior to physician's choice in patients with relapsed/refractory CLL, suggesting a more than 6 fold improvement in PFS and almost 3 fold improvement in OS. Results were consistent across all different physician chosen treatments and provides further evidence that ibrutinib improves both PFS and OS vs current and prior standard of care regimens. Figure 1. Adjusted Hazard ratio's for PFS and OS of physician's choice versus Ibrutinib (RESONATE) (Multivariate Cox proportional hazards regression) a. Progression-free survival b. Overall survival Figure 1. Adjusted Hazard ratio's for PFS and OS of physician's choice versus Ibrutinib (RESONATE) (Multivariate Cox proportional hazards regression). / a. Progression-free survival b. Overall survival Disclosures Österborg: Janssen Cilag: Research Funding. Asklid:Janssen Cilag: Research Funding. Diels:Janssen: Employment. Repits:Janssen Cilag: Employment. Söltoft:Janssen Cilag: Employment. Hansson:Jansse Cilag: Research Funding. Jäger:Janssen Cilag: Research Funding.

374 Peripheral Regulatory T Cells are Expanded but do not Impact Survival in Newly Diagnosed Glioblastoma

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 288-288
Author(s):  
Joseph D DiDomenico ◽  
Daniel Eduardo Oyon ◽  
Winward Choy ◽  
Jonathan B Lamano ◽  
Dorina Veliceasa ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Blood Leukocytes ◽  
Promote Tumor Growth ◽  
Standard Of Care Treatment

Abstract INTRODUCTION Regulatory T cells (Tregs) have an immunosuppressive function that can promote tumor growth in numerous malignancies. Prior studies have shown that Tregs as a fraction of the CD4+ T cell population are expanded within the tumor microenvironment and peripheral blood of GBM patients. Differing studies have shown mixed associations between the presence of intratumoral Tregs and GBM patient survival. Although circulating Tregs have been shown to impact survival in preclinical models of GBM, no clear association has been demonstrated clinically in patients. Here, we investigate the clinical impact of peripheral Treg expansion in newly diagnosed GBM patients receiving standard treatment. METHODS Peripheral blood leukocytes were isolated from 61 newly diagnosed GBM patients prior to surgery. Tregs (CD4+CD25+FoxP3+) were quantified by flow cytometry, and patients were divided into Treghi and Treglo subsets relative to the median. All patients underwent maximal safe resection followed by standard chemoradiation. Radiographic progression and overall survival were recorded. RESULTS >Peripheral Treg populations ranged from 0.3-14.3%, with a mean of 4.5%. Median progression free survival (PFS) for all patients was ¬¬9.5 months and median overall survival (OS) was 14.8 months. PFS for the Treghi and Treglo groups was 9.0 and 11.2 months, respectively (HR = 0.91; P = 0.77). OS for the Treghi and Treglo groups was 14.8 and 16.1 months, respectively (HR = 0.95; P = 0.89). Patients in the bottom quartile were compared to the top quartile without statistically significant differences in PFS (HR = 0.64; P = 0.33) or OS (HR = 0.58; P = 0.24). CONCLUSION In patients receiving standard of care treatment for newly diagnosed GBM, Treg expansion in peripheral blood does not significantly impact survival. As the use of immune checkpoint targeting therapies, including the Treg targets CTLA-4 and CD25, are increasingly used in the management of cancer, these findings should be strongly considered when designing studies for GBM.

Five-year overall survival (OS) in COLUMBUS: A randomized phase 3 trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients (pts) with BRAF V600-mutant melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9507-9507
Author(s):  
Reinhard Dummer ◽  
Keith Flaherty ◽  
Caroline Robert ◽  
Ana Maria Arance ◽  
Jan Willem de Groot ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Mek Inhibitor ◽  
Subsequent Treatment ◽  
Drug Discontinuation ◽  
Tolerability Profile

9507 Background: Combined BRAF/MEK inhibitor therapy has demonstrated benefits on progression-free survival (PFS) and OS and is standard of care for the treatment of advanced BRAF V600-mutant melanoma. Here we report a 5-year update from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, 577 pts with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to encorafenib 450 mg QD + binimetinib 45 mg BID (COMBO450), encorafenib 300 mg QD (ENCO300), or vemurafenib 960 mg BID (VEM). An updated analysis including PFS, OS, objective response rate (ORR; by blinded independent central review), and safety was conducted after minimum follow-up of 65.2 months (mo). Data are as is; study is ongoing. Results: At data cut-off (Sep 15, 2020), there were 131 (68%), 117 (60%), and 145 (76%) deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. The median OS (95% CI) and 5-year OS rate (95% CI) with COMBO450 were 33.6 (24.4–39.2) mo and 34.7% (28.0–41.5), respectively (median follow-up: 70.4 mo). The 5-year OS rate (95% CI) in COMBO450 pts who had normal lactate dehydrogenase (LDH) levels at baseline was 45.1% (36.5–53.2). Median OS and 5-year OS rates for ENCO300 and VEM, as well as for pts with normal and high LDH levels and > 3 organs involved at baseline, are shown in the table. For COMBO450, ENCO300, and VEM, the 5-year PFS rate was 22.9%, 19.3%, and 10.2%; ORR (95% CI) was 64.1% (56.8–70.8), 51.5% (44.3–58.8), and 40.8% (33.8–48.2); and the median duration of response (DOR) was 18.6, 15.5, and 12.3 mo, respectively. Safety results were consistent with the known tolerability profile of COMBO450. Additional efficacy and updated safety analyses will be presented. Following study drug discontinuation, the most common subsequent treatment in all arms was checkpoint inhibitors. Conclusions: Updated OS and DOR results with COMBO450 demonstrate continued long-term benefits in pts with BRAF V600-mutant melanoma. Clinical trial information: NCT01909453. [Table: see text]

scholarly journals Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial

2021 ◽  
Vol 100 (4) ◽  
pp. 1049-1058 ◽  
Author(s):  
James Russell ◽  
Angela Collins ◽  
Alexis Fowler ◽  
Mamatha Karanth ◽  
Chandan Saha ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Real World ◽  
Prognostic Score ◽  
Intensive Therapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Advanced Stage ◽  
Ct Guided ◽  
Positron Emission

AbstractTreatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial (“real-world”) patients, aged 16–59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18–59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.

scholarly journals Pembrolizumab Alone or Combined With Chemotherapy in Advanced NSCLC With PD-L1 ≥50%: Results of a Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ya Chen ◽  
Yanan Wang ◽  
Zhengyu Yang ◽  
Minjuan Hu ◽  
Yanwei Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Nsclc ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Programmed Death ◽  
Platinum Based Chemotherapy ◽  
Prospective Trials ◽  
Nsclc Patients

ObjectivesPembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy (PM) both become standard of care in patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50%. This study aimed to figure out the better treatment choice.MethodIn this retrospective analysis, we compared the clinical efficacy of PM and PC as first-line treatment in NSCLC patients with a PD-L1 ≥50% and negative for genomic alterations in the EGFR and ALK genes.ResultAmong the population, 115 patients received PC, and 91 patients received PM. Up to Dec 30, 2020, median follow-up was 17.13 months. The median progression-free survival (PFS) rates of PC and PM were 12.37 and 9.60 months (HR: 0.44, p &lt; 0.001), respectively. The median overall survival (OS) rates were NE and 28.91 months (HR: 0.40, p = 0.005), respectively. Subgroup analysis found that the PFS benefit of PC was evident in most subgroups excepting patients with brain metastasis. The 1-year overall survival rates of PC and PM were 89.3% and 76.1%, respectively. The ORR was 61.7 and 46.9% (p = 0.004), respectively.ConclusionIn patients with previously untreated, PD-L1 ≥50%, advanced NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard platinum-based chemotherapy seems to be the preferred treatment, which needs to be validated by further prospective trials.

scholarly journals Progression-Free Survival in Third-Line Treatment of Relapsed/Refractory Multiple Myeloma Among Patients with Who Have Received Prior Bortezomib and Immunomodulatory Drugs

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3311-3311
Author(s):  
Sundar Jagannath ◽  
Anuja Roy ◽  
Jonathan K Kish ◽  
Denise Globe ◽  
Orsolya Lunacsek ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Employment Equity ◽  
Free Survival ◽  
Treatment Regimens ◽  
Risk Of Progression ◽  
Study Population ◽  
Equity Ownership ◽  
Immunomodulatory Drug

Abstract Background: There are limited data on real-world treatment outcomes for novel agents used in the treatment of relapsed/refractory multiple myeloma (RRMM). These data are particularly important for patients who have already received bortezomib (BTZ) and an immunomodulatory drug (IMiD) given the lack of a standard of care in 3rd line and the costs of novel therapies including lenalidomide (LEN), carfilzomib (CFZ) and pomalidomide (POM). Methods: Data including patient and disease characteristics, treatment information and mortality data were collected from electronic medical records. RRMM patients diagnosed between 01/2007-08/2014 having received at least three treatment regimens (not including maintenance) were selected from the International Oncology Network (ION) database. Treatment regimens were aggregated into 8 mutually exclusive categories. Progression-free survival (PFS), based on physician reported date of progression, was calculated by treatment regimen overall and for the subgroup of patients who had prior BTZ and IMiD exposure. A multivariate proportional hazard model was used to estimate the risk of progression or death in the subgroup adjusting for age, gender, race, year of diagnosis, ISS stage, presence of cytogenetic abnormality, immunoglobulin type, receipt of stem-cell transplant (SCT), ECOG status and comorbidities at diagnosis. Results: There were 391 patients that met inclusion criteria. Mean age at diagnosis was 68 years, 46.9% being ISS III and 55.5% were classified as IgG. Median duration of follow-up was 36.1 months with 45% of patients being deceased by the end of follow-up. SCT information was available for 218 patients: 25.2% were deemed ineligible, 46.8% received an SCT and 28% of eligible patients had no evidence of receiving a SCT. BTZ and an IMiD were received by 239/391 (61.1%) patients prior to 3rd line. PFS in 3rd -line for the overall study population and the subgroup are presented in Table 1. For the subgroup, the median PFS in 3rd-line among regimens with at least 10 patient was: BTZ monotherapy ± non-IMiD - 7.3 months; LEN monotherapy or ± non-proteasome inhibitor (PI) - 4.9 months; BTZ + IMiD - 7.3 months; CFZ monotherapy ± IMiD - 3.7 months; and POM monotherapy ± PI - 5.8 months. Although not statistically significant, risk of progression or death after adjustment for baseline demographic and clinical characteristics was lower for BTZ + IMiD and other chemotherapies and higher for LEN monotherapy or ± non-PI, CFZ monotherapy ± IMiD and POM monotherapy ± PI compared to BTZ mono ± non-IMID (Table 1). Conclusions: These data are the first recent real-world treatment outcomes in RRMM. For BTZ-, LEN-, and POM-containing regimens, PFS was non-significantly shorter in 3rd-line for those patients with prior BTZ and IMiD treatment compared to the overall study population. For the subgroup, the results of the multivariate proportional hazards model showed no significant difference in the risk of progression or death in 3rd-line for patients with prior BTZ and IMiD therapy compared to other treatment regimens. As such, there remains a significant unmet need for novel treatment regimens which significantly improve PFS for the subgroup of patients who have received prior treatment with both BTZ and an IMiD. Table 1. Overall Patients with prior BTZ and IMiD¥ 3rd - Line Treatment Regimen N PFS (95% CI) N PFS (95% CI) HR p-value BTZ mono ± non-IMID 128 9.1 (7.1 - 10.9) 69 7.3 (4.2 - 10.8) REF - LEN mono ± non-PI 88 7.0 (4.7 - 10.6) 45 4.9 (3.0 - 8.6) 1.23 0.43 BTZ + IMID (thalidomide or lenalidomide) 59 9.4 (5.3 - 12.3) 39 7.3 (5.0 - 15.0) 0.84 0.55 THAL mono ± non-PI 12 8.5 (1.4 - 16.4) 7 9.8 (0.1 - 50.4) 0.94 0.89 MEL mono ± non-IMiD, non-PI 19 8.3 (3.4 - 13.2) 7 3.4 (0.6 - NR) 1.16 0.78 MEL + THAL 5 25.2 (0.7 29.4) 4 25.2 (0.7 - 29.4) * * CFZ mono ±IMID / Other † 37 3.6 (2.6 - 8.4) 34 3.7 (2.8 - 8.4) 1.13 0.68 POM mono ± PI / Other 17 9.6 (1.6-13.8) 15 5.8 (1.4 - 13.8) 1.18 0.68 Other Chemotherapies 26 5.6 (2.1 -13.3) 19 7.9 (1.9 - 14.0) 0.95 0.87 ¥ Steroids (dexamethasone or prednisone) may have been given in conjunction with any of the therapies per usual standard of care. † Includes patients treated with combination CFZ + POM. * Patients combined with "Other Chemotherapies" in model. Key: BTZ - bortezomib; CI - confidence interval; CFZ - carfilzomib; IMiD - immunomodulatory drug; LEN - lenalidomide; MEL - melphalan; NR - not reached; PI - proteasome inhibitor; POM - pomalidomide; THAL - thalidomide. Disclosures Jagannath: Janssen: Honoraria; Celgene: Honoraria; Merck: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria. Roy:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Kish:Xcenda LLC: Employment. Globe:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lunacsek:Xcenda LLC: Employment. Eaddy:Xcenda LLc: Employment. Kuriakose:Novartis: Employment, Equity Ownership. Willey:Xcenda LLc: Employment. Siegel:Celgene Corporation: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Merck: Speakers Bureau.

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