Temozolomide Alone or Combined with Capecitabine for the Treatment of Metastatic Neuroendocrine Neoplasia: a “Real World” data analysis

Background: Neuroendocrine neoplasia (NEN) are a rare group of tumors with different prognosis and response to therapy. Their heterogeneity is dependent on the site of origin, morphology and Ki67. Temozolomide (TEM) appears to be active in metastatic NENs (mNENs) but there is limited evidence about its efficacy in gastrointestinal NENs. We analyzed “real-world” data on the use of TEM alone or in association with capecitabine (CAPTEM) in patients with mNENs. Patients and Methods: One hundred consecutive patients with advanced NENs treated with TEM or CAPTEM between 2009 and 2019 were included. A pre-treatment tumor growth rate (TGR0) was calculated. Overall survival (OS), progression-free survival (PFS), tolerance, objective response rate (ORR) and disease control rate (DCR) were analyzed. A propensity score analysis and inverse probability of treatment weights for Cox-regression models were used. Results: TEM-based therapy was administered to 95 patients (26.3% CAPTEM and 83.7% TEM) with a median age of 59 years (range 26-85) years. ECOG performance status was 0-2. Carcinoid syndrome was reported in 12 (12.6%) patients. Twenty (21.1%) patients with grade (G) 3 neuroendocrine carcinoma (NEC) and 9 (9.4%) with G3 neuroendocrine tumors (NET) were included in the analysis. Median PFS of the entire group was 10.4 months (95% confidence interval (CI):6.0-11.5). In multivariate analysis, a higher risk of progression was observed for NEC G3 patients (hazard ratio (HR) 2.70, 95%CI:1.25-5.84) and for a TGR ≥19.55 (HR:2.53, 95%CI:1.45-4.40). Median OS was 23.4 months (95%CI: 17.0-29.0) and was similar in both treatment groups (23.9 vs. 20.5 months for TEM and CAPTEM, respectively, p =0.585). In multivariate analysis, TGR ≥19.55 was associated with a higher risk of death (HR:2.18, 95%CI:1.16-4.11) than TGR<19.55, as was NEC G3 (HR: 2.42, 95%CI:1.04-5.59) with respect to NETs. No differences in terms of mPFS or mOS were seen in relation to the primary site of disease. In the 86 patients evaluable for response, ORR was 44.1% and the DCR was 70.9%. Mild adverse events (grade I-II) included anemia, neutropenia and headache. Rare cases of grade 3 neutropenia and thrombocytopenia were recorded. Conclusions: TEM-based regimens are associated with a high DCR and a relatively tolerable toxicity profile in NEN of pancreatic, intestinal and lung origin. Further investigation of these specific NETs is warranted in prospective clinical trials.

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1175P Temozolomide alone or combined with capecitabine for the treatment of metastatic neuroendocrine neoplasia: A “Real World” data analysis

Annals of Oncology ◽

10.1016/j.annonc.2020.08.1388 ◽

2020 ◽

Vol 31 ◽

pp. S778

Author(s):

A. Bongiovanni ◽

C. Liverani ◽

F. Foca ◽

M. Signoretti ◽

F. Pieri ◽

...

Keyword(s):

Data Analysis ◽

Real World ◽

Real World Data ◽

World Data ◽

Neuroendocrine Neoplasia

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Value of cabozantinib in the treatment of advanced metastatic clear cell renal cell carcinoma (ccRCC): Real-world data from a single Korean institution.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16578 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16578-e16578

Author(s):

Seoyoung Lee ◽

Seul-Gi Kim ◽

Sejung Park ◽

Jeehyun Lee ◽

Seung-Hoon Beom ◽

...

Keyword(s):

Real World ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Cancer Center ◽

Second Line ◽

Real World Data ◽

World Data ◽

Third Line ◽

Grade 3

e16578 Background: Cabozantinib is a multitarget tyrosine kinase inhibitor and getting attention in these days through its combination with immune checkpoint inhibitors. In this article, we analyze the efficacy of cabozantinib in patients with metastatic ccRCC in Korean who had progression after 1 or more VEGFR TKI therapies. Methods: Seventy-five patients from Jan.2019 to Dec. 2021 at Yonsei Cancer Center who had received cabozantinib treatment in second to fourth line of therapy were retrospectively reviewed. The primary endpoint was PFS. The secondary outcomes were the response rate, disease control rate (DCR), and OS. The evaluable subjects for efficacy were those who had at least one response evaluation. Results: Among 75 patients, 57 (76.0%) were male and median age was 59 years (range 33-81). Median follow up time was 12.1 months. There were 22 (29.3%) patients of second line, 38 (50.7%) of third line and 15 (20.0%) of fourth line of treatment. Median PFS was 5.6 months (95% CI, 4.6-6.6). Median OS was 13.6 months (95% CI, 5.0-22.2). The PFS based on the line of treatment was 4.7 months for second line, 5.6 months for third line and 12.0 months for 4th line. Proportion of patients who were previously treated with ICI was different between treatment line groups and showed increasing trend toward later line; 13.6% of second line, 31.6% of third line, and 66.7% of fourth line, respectively. The objective response rate was 8.0% with 6 patients of partial response. The DCR was 69.3%. The major toxicities were similar with the western population and most of them were less than CTCAE grade 3. Most common grade 3 or 4 AEs were anemia, hand-foot syndrome, fatigue, and stomatitis. There were no grade 5 AEs. Conclusions: Our results demonstrate that cabozantinib is an effective treatment option after first line TKI in Korean ccRCC patients with manageable toxicities. Notably, its tolerability in the advanced line of treatment and synergy with ICIs are suggested in this study despite heterogeneous patients of real world setting. This is the first real world data with cabozantinib in Asian patients.

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Association of baseline characteristics and survival in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (CPIs): Real-world evidence.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21625 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21625-e21625

Author(s):

Danielle Crawley ◽

Kerri Beckmann ◽

Saranya Ravindra ◽

Debra Hannah Josephs ◽

James F. Spicer ◽

...

Keyword(s):

Brain Metastases ◽

Real World ◽

Checkpoint Inhibitors ◽

Definitive Treatment ◽

Real World Data ◽

World Data ◽

Risk Of Death ◽

Mutational Status ◽

Increased Risk ◽

Baseline Characteristics

e21625 Background: CPIs including antibodies to programmed death-1 (PD-1) and its ligand anti PD-L1 are associated with superior overall survival (OS) in NSCLC. PDL1 is an imperfect predictive biomarker. We have examined real world data to identify additional factors associated with clinical benefit. Methods: 96 consecutive NSCLC patients (pts) were treated with CPIs at our institution. Multivariate cox proportional hazard regression models were used to examine the associations between OS and baseline characteristics including age, sex, histology, PDL1 status, performance status (PS), steroid use and brain metastases. Results: 93% (89/96) of pts received pembroluzimab, 6 (6%) nivolumab, and 1 (1%) atezoluzimab. All pts had metastatic disease (68% adenocarcinoma). 15% had PS 0, and 70% PS1. 11 of the 96 pts had brain metastases prior to CPI, 4 (37%) had whole brain radiotherapy, 2 (18%) targeted radiotherapy, 2 (18%) resection with radiotherapy and 3 (27%) had no definitive treatment for brain metastases. After multivariate analysis those with PS 1-2 had an increased risk of death (PS = 1 HR 2.74, 95% CI 1.11-6.72; PS = 2 3.61, 95% CI 1.28-10.15) compared with PS 0. Outcomes for pts receiving corticosteroids at the time of initiation of CPI were also inferior (HR 2.29, 95% CI 1.10-4.74) compared to those who were not. Conversely those who had brain metastasis diagnosed prior to commencing CPI had superior OS (HR 0.29 95% CI: 0.11-0.76). No statistically significant association was seen with age, gender, histology, stage at diagnosis, smoking or mutational status. PDL < 50% compared to > 50% was associated with an increased risk of death (HR 1.53 95% CI: 0.90-2.60) though it was not statistically significant. Conclusions: Here we show, using real world data, that PS and use at baseline of oral corticosteroids are associated with inferior OS with CPI treatment for NSCLC, in line with reports from large clinical trials. We show that baseline brain metastases are associated with improved outcomes. This may be explained by survivor bias, in that those who are successfully treated for brain disease, remain PS ≤2 and are able to commence CPI represent a highly selected group.

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Propensity score analysis of overall survival between first‐ and second‐generation EGFR‐TKIs using real‐world data

Cancer Science ◽

10.1111/cas.14560 ◽

2020 ◽

Vol 111 (10) ◽

pp. 3705-3713

Author(s):

Kentaro Ito ◽

Kenta Murotani ◽

Akihito Kubo ◽

Eiji Kunii ◽

Hirokazu Taniguchi ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Real World ◽

Second Generation ◽

Propensity Score Analysis ◽

Real World Data ◽

World Data ◽

Score Analysis ◽

First And Second Generation ◽

Egfr Tkis

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Novel risk stratification algorithm for estimating the risk of death in patients with relapsed multiple myeloma: external validation in a retrospective chart review

BMJ Open ◽

10.1136/bmjopen-2019-034209 ◽

2020 ◽

Vol 10 (7) ◽

pp. e034209 ◽

Cited By ~ 1

Author(s):

Roman Hájek ◽

Sebastian Gonzalez-McQuire ◽

Zsolt Szabo ◽

Michel Delforge ◽

Lucy DeCosta ◽

...

Keyword(s):

Multiple Myeloma ◽

Risk Stratification ◽

Real World ◽

Goodness Of Fit ◽

Cox Regression ◽

External Validation ◽

Risk Groups ◽

Real World Data ◽

Risk Of Death ◽

Increased Risk

Objectives and designA novel risk stratification algorithm estimating risk of death in patients with relapsed multiple myeloma starting second-line treatment was recently developed using multivariable Cox regression of data from a Czech registry. It uses 16 parameters routinely collected in medical practice to stratify patients into four distinct risk groups in terms of survival expectation. To provide insight into generalisability of the risk stratification algorithm, the study aimed to validate the risk stratification algorithm using real-world data from specifically designed retrospective chart audits from three European countries.Participants and settingPhysicians collected data from 998 patients (France, 386; Germany, 344; UK, 268) and applied the risk stratification algorithm.MethodsThe performance of the Cox regression model for predicting risk of death was assessed by Nagelkerke’s R2, goodness of fit and the C-index. The risk stratification algorithm’s ability to discriminate overall survival across four risk groups was evaluated using Kaplan-Meier curves and HRs.ResultsConsistent with the Czech registry, the stratification performance of the risk stratification algorithm demonstrated clear differentiation in risk of death between the four groups. As risk groups increased, risk of death doubled. The C-index was 0.715 (95% CI 0.690 to 0.734).ConclusionsValidation of the novel risk stratification algorithm in an independent ‘real-world’ dataset demonstrated that it stratifies patients in four subgroups according to survival expectation.

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Real-world data on camrelizumab in digestive system cancers: a retrospective observational study

Medical & Clinical Research ◽

10.33140/mcr.06.09.01 ◽

2021 ◽

Vol 6 (9) ◽

Keyword(s):

Gastric Cancer ◽

Real World ◽

Digestive System ◽

Response Rate ◽

Cox Regression ◽

Objective Response ◽

Progression Free Survival ◽

Real World Data ◽

Cox Regression Analysis ◽

Best Response

Objective: To explore the clinical efficacy and safety of camrelizumab in the treatment of digestive system malignancies in the real world. Methods: A retrospective study was designed. A total of 34 patients with advanced gastrointestinal cancer who received camrelizumab treatment in the xx hospital from July 2019 to May 2020 were included. The follow-up endpoint was set for October 30, 2020. The primary endpoint was objective response rate (ORR) and safety. Secondary endpoint measures included progression-free survival (PFS), and overall survival (OS). Cox regression was used for the analysis of factors associated with PFS. Results: As the best response, only 5 patients achieved a partial response and 10 patients had disease progression, with an ORR of 14.31%. Compared with gastric cancer, the ORR of esophageal cancer (3.0% vs 0.0%) (P<0.05). The PFS was 4.5 months (2-10 months). OS ranged from 4 to 11 months, and median OS has not been reached. Multivariate Cox regression analysis showed that gastric cancer (HR=1.695, 95% CI:11.216–2.435, P<0.05) was associated with still shorter PFS, and camrelizumab combined with other drugs (HR=0.512, 95% CI: 0.095–0.737, P<0.01) was associated with PFS in patients. The most common AEs were anemia (41.2%, 14/34) in all grades 1 to 2. Grade 3 AEs occurred in 3 patients (2.9%), including 1 case of immune pneumonitis, 1 case of hemangioma, and 1 case of transaminase increased. Other adverse events included diarrhea, nausea, neutropenia, thrombocytopenia, reactive cutaneous capillary proliferation (RCCEP), fatigue, and hypothyroidism, all of which did not exceed 12%. Conclusion: Camrelizumab is effective and safe in the treatment of patients with digestive system malignancies, but the overall response rate is limited.

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Real-World Data on Clinical Features, Outcomes, and Prognostic Factors in Multiple Myeloma from Miyazaki Prefecture, Japan

Journal of Clinical Medicine ◽

10.3390/jcm10010105 ◽

2020 ◽

Vol 10 (1) ◽

pp. 105

Author(s):

Keiichi Akizuki ◽

Hitoshi Matsuoka ◽

Takanori Toyama ◽

Ayako Kamiunten ◽

Masaaki Sekine ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Real World ◽

Initial Treatment ◽

Staging System ◽

Novel Agents ◽

Real World Data ◽

World Data

The prognosis of multiple myeloma (MM) has improved with the introduction of novel agents. These data are largely derived from clinical trials and might not reflect real-world patient outcomes accurately. We surveyed real-world data from 284 patients newly diagnosed with MM between 2010 and 2018 in Miyazaki Prefecture. The median follow-up period was 32.8 months. The median age at diagnosis was 71 years, with 68% of patients aged >65 years. The International Staging System (ISS) stage at diagnosis was I in 18.4% of patients, II in 34.1%, and III in 47.5%. Bortezomib-containing regimens were preferred as initial treatment; they were used in 147 patients (51.8%). In total, 80% of patients were treated with one or more novel agents (thalidomide, lenalidomide, or bortezomib). Among 228 patients who were treated with novel agents as an initial treatment, the overall response rate (partial response (PR) or better) to initial treatment was 78.4%, and the median time to next treatment (TTNT) was 11.6 months. In the multivariate analysis, PR or better responses to initial treatment were independently favorable prognostic factors for TTNT. The median survival time after initial therapy for patients with novel agents was 56.4 months and 3-year overall survival (OS) was 70.4%. In multivariate analysis, ISS stage I/II disease and PR or better response to initial treatment, and autologous stem cell transplantation (ASCT) were identified as independent prognostic factors for overall survival (OS).

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Risk factors for progression or death in ovarian cancer patients who completed first-line platinum treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5548 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5548-5548

Author(s):

Shannon Neville Westin ◽

Melinda Louie-Gao ◽

Enkhe Badamgarav ◽

Mohan V. Bala ◽

Premal H. Thaker

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Prognostic Factors ◽

Real World ◽

Residual Disease ◽

Stage Iii ◽

First Line ◽

Real World Data ◽

World Data ◽

Risk Of Death

5548 Background: Limited real-world information is available in ovarian cancer (OC) regarding prognostic factors for disease progression or death after initial treatment. Here, we assessed potential prognostic risk factors in OC patients (pts) who completed first-line (1L) platinum-based chemotherapy (CT) using real-world data. Methods: This retrospective study identified 5535 pts diagnosed with OC from January 2011–October 2018 from the Flatiron database, a longitudinal, demographically and geographically diverse database derived from health records from > 265 cancer clinics and > 2 million US cancer pts. Stage III/IV OC pts who completed 1L platinum-based CT after primary debulking or interval debulking surgery were included. Pts who received a poly(ADP-ribose) polymerase inhibitor (PARPi) in 1L treatment or as maintenance therapy after 1L treatment were excluded. Cox proportional hazards model was used to assess the association between baseline factors (neoadjuvant CT, disease stage, residual disease, BRCA status, ECOG, age, platelet count, hemoglobin, and neutrophil count) and time to next treatment (TTNT; a proxy for progression-free survival) or overall survival (OS) in these pts. Results: 1064 of 5535 pts were eligible per our inclusion/exclusion criteria. Neoadjuvant treatment, stage of disease, residual disease after surgery, and BRCA mutation ( BRCAmut) status were significant prognostic factors for either TTNT or OS. Neoadjuvant chemotherapy pts had a shorter TTNT (hazard ration [HR] = 1.37; P= .001) and OS (HR = 1.64; P= .0002) than pts who underwent primary surgery after adjusting for other covariates. Stage IV pts had a shorter TTNT (HR = 1.26; P= .01) and OS (HR = 1.24; P= .09) than stage III pts. OS was also worse in pts with vs without residual disease (HR = 1.27; P= .04) and worse in BRCAwt than BRCAmut pts (HR = 1.37; P= .10). Conclusions: In this retrospective analysis of a real-world data set, BRCAwt status was associated with higher risk of death. Receipt of neoadjuvant CT, higher stage of disease at diagnosis, or presence of residual disease after surgery were also associated with a shorter TTNT or higher risk of death. These real-world data confirm previously identified prognostic factors.

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Upfront Rituximab Maintenance after Induction Therapy Improves Outcome and Reduces the Risk of Histological Transformation in Patients with Follicular Lymphoma - Real World Data from a Danish Population-Based Cohort

Blood ◽

10.1182/blood.v128.22.1783.1783 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1783-1783

Author(s):

Charlotte Madsen ◽

Michael Roost Clausen ◽

Maja Ludvigsen ◽

Trine Lindhardt Plesner ◽

Francesco d'Amore

Keyword(s):

Multivariate Analysis ◽

Follicular Lymphoma ◽

Real World ◽

B Cell Lymphoma ◽

Population Based ◽

Induction Treatment ◽

Real World Data ◽

World Data ◽

Rituximab Maintenance ◽

Histological Transformation

Abstract Introduction: In Denmark, as in most other Western countries, follicular Lymphoma (FL) is the second most common lymphoma entity. Although still regarded as an incurable condition, FL is characterized by an indolent clinical course, a natural history of recurrent relapses and in some cases transformation to an aggressive histology (HT). The addition of the anti CD20 antibody Rituximab to chemotherapy (r-chemo) has had a profoundly favorable impact on the time to relapse, survival and possibly also transformation rates (N. Wagner-Johnston et al, Blood, 2015; C. Sarkozy et al, JCO, 2016). During the last decade maintenance with Rituximab after initial immuno-chemotherapy, has been introduced with the hopes of further improving outcome for patients with FL. Aims: In this population-based study of real world data, we investigated the effect of upfront Rituximab maintenance (RM) on progression, survival and HT in FL patients. Patients and Methods: Patients diagnosed with histologically verified FL or Diffuse Large B-cell Lymphoma (DLBCL) in Denmark from 2000-2015 were identified through the National Danish Pathology Registry. Pathology reports were reviewed for patients diagnosed with both FL and DLBCL during the study period. HT was defined as initial biopsy proven FL diagnosis followed, in the same patient, by a subsequent biopsy-verified FL grade 3B or DLBCL. The identified patient cohort was cross-linked with the Danish Lymphoma Registry (LYFO). From this population, patients were included if meeting the following criteria: (i) completed first-line induction treatment with r-chemo, (ii) alive and eligible for RM at the time of clinical evaluation after induction treatment, and (iii) no evidence of HT at the same time point. Decision of treatment-free follow up or RM was applied according to local guidelines (RM was introduced at different time-points at different lymphoma-treating tertiary centers in Denmark). The RM-schedule consisted of 375 mg/m2 intravenous or subcutaneous every other month for 2 years. Statistical methods: Patient characteristics were compared using Fisher's exact or Student's t test. All time related end-points were estimated by Kaplan-Meier time-to-event analyses and compared using the log-rank test. Overall survival (OS) was defined from the date of FL diagnosis to the date of death by any cause or censoring; Progression-free survival (PFS) was calculated from the date of FL diagnosis to the date of progression/relapse or censoring. Time-to-transformation (TTT) was calculated from the date of FL-diagnosis to the date of biopsy proven HT. Factors of potential clinical relevance were tested in a multivariate analysis using a Cox proportional Hazards model. Results: 722 patients had completed their first Rituximab-containing induction treatment; 364 patients were consolidated with RM while 358 were not. The two treatment cohorts (no-RM vs. RM) were comparable in terms of sex and age distribution as well as performance score and LDH-elevation. Patients receiving RM had more often advanced Ann Arbor stage (p<0.001), higher FLIPI-score (p<0.001), heavier tumor burden (p<0.001) and bone marrow involvement (p=0.012). As compared to no-RM patients, those consolidated with RM had a significantly improved 5-year OS (83% vs. 90%; p=0.003) and PFS (63% vs. 72%; p<0.001) at univariate level and confirmed in multivariate analysis (fig. 1). Similarly, the rate of HT was reduced in RM treated patients (10% vs. 6%; p=0.067) and the mean TTT was prolonged (1.8 yrs vs. 2.7 yrs; p=0.052). Conclusions: Upfront consolidation with RM after initial treatment with r-chemo in patients with FL results in improved OS and PFS. Furthermore, after RM HT seems to occur less frequently and the event is significantly postponed. Disclosures No relevant conflicts of interest to declare.

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OP447 Feasibility And Validity Of Real-World Data As Evidence Of Effectiveness - Experience From Breast Cancer Care In Scotland

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462320001117 ◽

2020 ◽

Vol 36 (S1) ◽

pp. 9-10

Author(s):

Ewan Gray ◽

Joachim Marti ◽

David H Brewster ◽

Jeremy C Wyatt ◽

Peter S Hall

Keyword(s):

Breast Cancer ◽

Real World ◽

Early Stage ◽

Prognostic Score ◽

Primary Source ◽

Real World Data ◽

Treatment Benefit ◽

World Data ◽

Underrepresented Groups ◽

Risk Of Death

IntroductionData from randomized controlled trials (RCTs) are the primary source for health technology assessment (HTA) however these are limited by strict patient inclusion criteria, leading to concerns about whether treatment benefit estimates are accurate for all patients (generalizability). Real-World Data (RWD) have been proposed as a solution however as these are observational data there is additional potential for bias when estimating treatment effectiveness. To maximize the utility of RWD it is useful to consider the whole process of evidence generation and robustly address issues of feasibility and validity.MethodsA series of complementary studies investigated whether population-based routinely collected health data from Scotland are suitable for estimating the effectiveness of chemotherapy for early breast cancer. Firstly, a prognostic score was validated in this population. Secondly, a comparison of RWD and randomized trial effectiveness estimates was made to investigate feasibility and validity of several methods – Propensity Score Matching (PSM), Instrumental variables (IV) and Regression Discontinuity. Finally, effectiveness estimates in trial underrepresented groups were produced.ResultsPSM and IV were feasible and produced results in relatively close agreement with randomized data. Effectiveness estimates in trial underrepresented groups (women over 70 years and women with high comorbidity) were consistent with an approximate one-third reduction in the risk of death from breast cancer. This is equivalent to approximately a 3–4 percentage point difference in all cause mortality over 10 years in these groups.ConclusionsRWD are a feasible for generating estimates of effectiveness of adjuvant chemotherapy in early stage breast cancer. The process of using RWD for this purpose should include careful assessment of data quality and comparison of alternative strategies for causal identification in the context of available randomized data.

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