scholarly journals Genomic-guided individualized precision therapy in refractory metastatic solid tumor patients with extensively poor performance status: A Chinese single institutional prospective observational real-world study

2019 ◽  
Vol 30 ◽  
pp. v765
Author(s):  
H. Wang
Keyword(s):  
Solid Tumor ◽  
Real World ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Tumor Patients ◽  
Metastatic Solid Tumor ◽  
Precision Therapy

Trends in checkpoint inhibitor therapy for advanced urothelial cell carcinoma (aUC) at the end of life: Insights from real-world practice.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Ravi Bharat Parikh ◽  
Matt D. Galsky ◽  
Bishal Gyawali ◽  
Fauzia Riaz ◽  
Tara Laura Kaufmann ◽  
...  
Keyword(s):  
End Of Life ◽  
Real World ◽  
Systemic Therapy ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Poor Performance ◽  
Nonparametric Tests ◽  
Poor Performance Status ◽  
National Guidelines ◽  
Health Database

395 Background: National guidelines recommend against chemotherapy use at the end of life. Five CPIs are now approved for aUC. We hypothesized that oncologists may have a lower threshold to initiate CPI in patients (pts) at the end of life, particularly among pts with poor performance status (PS), because of the perceived favorable toxicity profile of CPI. Methods: We conducted a secular trend analysis using the Flatiron Health Database, a large real-world electronic medical record-derived dataset. We used nonparametric tests of trend (p values reported as ptrend) to evaluate quarterly proportions of pts initiating CPI, chemotherapy, or no systemic therapy within 30 and 60 days of death, among 2959 pts diagnosed with aUC from 2015 to 2017. Results: 1637 pts died during follow-up and were eligible for analysis. 278 (17.0%) and 488 (29.8%) pts initiated a new line of systemic therapy in the last 30 and 60 days of life, respectively. The quarterly proportion of CPI initiators within 60 days of death increased from 1.0% to 23% during the study period ( ptrend < 0.001), with corresponding decreases in chemotherapy initiation and no systemic therapy. After CPI approval in mid-2016, CPI initiation significantly increased among pts with Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 ( ptrend = 0.02) but did not significantly change among pts with PS 0-1. Initiation of any systemic therapy at the end of life doubled (17.4% to 34.8%) over the study period, driven largely by end-of-life CPI use. Compared to chemotherapy initiators, CPI initiators had slightly worse PS (table). Conclusions: In patients with aUC, there has been a dramatic rise in CPI initiation at the end of life particularly among pts with poor PS. Existing guidelines on systemic therapy initiation near the end of life should account for the increasing use of CPI. [Table: see text]

scholarly journals Real world clinical outcomes of adjuvant sequential chemoradiation in patients with gallbladder carcinomas with poor performance status

2020 ◽  
Vol 38 (4) ◽  
pp. 262-269
Author(s):  
Rakesh Kapoor ◽  
Kannan Periasamy ◽  
Rajesh Gupta ◽  
Arun Yadav ◽  
Divya Khosla
Keyword(s):  
Clinical Outcomes ◽  
Real World ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status

Effect of first-line pembrolizumab treatment in individuals with advanced non-small cell lung cancer and poor performance status.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18796-e18796
Author(s):  
Rajwanth Veluswamy ◽  
Jiayi Ji ◽  
Liangyuan Hu ◽  
Xiaoliang Wang ◽  
Cardinale B. Smith ◽  
...  
Keyword(s):  
Treatment Group ◽  
Real World ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Poor Performance ◽  
Smoking History ◽  
Poor Performance Status ◽  
First Line ◽  
Inverse Probability ◽  
Ecog Ps

e18796 Background: There is limited evidence supporting the optimal use of immune checkpoint inhibitors (ICIs) in NSCLC patients with poor performance status (PS), as clinical trials exclude these patients. In this study, we use real-world oncology data to determine the impact of first line pembrolizumab vs. no treatment in high PD(L)-1 expressing cancers in individuals with advanced NSCLC and ECOG PS ≥2. Methods: We performed a retrospective cohort study of patients with advanced NSCLC with ECOG PS ≥2 between 09/01/2014 and 02/18/2020, using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients were included if they were PD(L)-1 high (≥50%) and had clinical and treatment information recorded within 90 days of diagnosis. Real-world overall survival (rwOS) was defined as time from diagnosis to death (censored at last EHR activity). Median rwOS was estimated using weighted Kaplan-Meier methods. A marginal Cox structural model with inverse probability of treatment weighting was used to adjust for selection bias and estimate the effectiveness of pembrolizumab. The inverse probability weights were estimated using an ensemble machine learning technique, Super Learner, based on age, gender, race, practice type and smoking history. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Stratified analysis was conducted by ECOG PS (2 vs >2). Results: 217 (16%) individuals with advanced NSCLC and high PD(L)-1 expression received no treatment, compared to 546 (39%) individuals who received 1L pembrolizumab. The no-treatment group had a lower proportion of ECOG 2 compared to the pembrolizumab group (Table). Median rwOS in the no-treatment group was 2.4 months, compared to 7.1 months in the pembrolizumab group (p<0.001). In unadjusted survival analyses in the entire cohort and in cohorts stratified by ECOG status, treatment with pembrolizumab was associated with a significantly lower risk of death (hazard ratio [HR]: 0.38, 95% Confidence Interval [CI]: 0.31-0.45). In adjusted analyses, individuals treated with pembrolizumab had improved survival (HR: 0.40, 95% CI: 0.35-0.45). Conclusions: Our analysis of real-world clinical oncology data demonstrated that 1L treatment with pembrolizumab was associated with significantly improved rwOS among individuals with ECOG ≥ 2. [Table: see text]

Precision oncology in pancreatobiliary cancers: A longitudinal study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 399-399
Author(s):  
Meena Sadaps ◽  
Bassam N. Estfan ◽  
Davendra Sohal ◽  
Alok A. Khorana
Keyword(s):  
Clinical Trials ◽  
Solid Tumor ◽  
Performance Status ◽  
Cleveland Clinic ◽  
Poor Performance ◽  
Tumor Board ◽  
Poor Performance Status ◽  
Precision Oncology ◽  
Advanced Cancer Patients ◽  
Off Label

399 Background: Precision oncology – the use of next-generation sequencing (NGS) to identify therapeutic options for advanced cancer patients – is being used widely, but its utility in patients with pancreatobiliary (PB) cancers has not been studied systematically. We evaluated the prevalence of actionable alterations and their impact on therapeutic decision-making in patients with PB cancers. Methods: We conducted a retrospective cohort study of consecutive patients seen at the Cleveland Clinic between 2013 and 2016 with incurable solid tumor malignancies, in whom FoundationOne™ (Cambridge, MA) NGS was ordered. All results were reviewed at a multidisciplinary genomics tumor board (GTB), which determined actionability and made therapeutic recommendations. Treatment decisions (on label, off label, or clinical trials) based on said recommendations were reviewed. Results: The study population was 600 patients, of whom 53 had PB cancers. For these 53, median age was 59.6 years; 62.2% (33/53) were female; 86.8% (46/53) were Caucasian. Eight samples (15.1%) had inadequate tissue; of 45 resulted cases, 21 (46.7%) were recommended treatment, including clinical trials (n = 19) and off-label drugs (n = 2). The most common targets for therapy were FGFR (5/21) and CDKN2 (3/21). Of 21 patients with recommendations, only two (9.5%) received genomics-driven therapy, compared with 31.7% (86/271) of patients with other solid tumor malignancies (p = 0.03). One received an IDH1 inhibitor, and one received dabrafenib and trametinib for a BRAF alteration; both on clinical trials. At time of last follow-up, best responses were unknown and partial response, respectively. Unavailability of clinical trials in the vicinity (9.5%), and clinical trial ineligibility, mainly due to poor performance status (9.5%), were common reasons for lack of actionability. Conclusions: Benefit from precision oncology in the PB population is low, with only 4.4% (2/45) of patients with NGS results eventually receiving genomics-driven therapy. Benefit to patients will not improve until access to clinical trials is enhanced and patients are evaluated for these trials earlier in the course of their disease, when their performance status is likely to be higher.

Chromosome 1 abnormalities and clinical outcomes in multiple myeloma in the era of novel agents.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8044-8044
Author(s):  
Smith Giri ◽  
Scott F. Huntington ◽  
Rong Wang ◽  
Amer Methqal Zeidan ◽  
Nikolai Alexandrovich Podoltsev ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Cox Regression ◽  
Performance Status ◽  
Poor Performance ◽  
Total Sample ◽  
Chromosome 1 ◽  
Poor Performance Status ◽  
Cox Regression Analysis ◽  
Entire Cohort

8044 Background: Abnormalities of chromosome 1 (C1A) are common genetic mutations in patients (pts) with Multiple Myeloma (MM). While several small studies have reported worse outcomes for C1A, the prevalence, real-world treatment and outcomes for pts with C1A are unknown. Methods: We used the Flatiron Health Electronic Health Record (EHR)-derived database to identify pts with newly diagnosed MM from 01/2011 to 03/2018 with Fluorescence In situ Hybridization (FISH) testing within 90 days of diagnosis and defined lines of therapy. We identified pts with C1A and other high-risk mutations (HRM; 17p deletion, t14;16 and t4;14). Pts were followed until 3/31/2018 or death. The primary outcome was overall survival (OS). We used Kaplan Meier methods and compared OS for pts with/without C1A using log-rank tests stratified for HRM. We used Cox regression analysis to compare OS across groups, adjusting for age, gender, performance status, stage, HRM and treatment (triple regimen vs other). Results: The total sample included 3,578 pts: median age at diagnosis was 69 yrs (IQR 31-85), with 54% males and 60% whites. IgG(57%) and IgA(22%) were the most common M-protein subtypes. At baseline, 844 (24%) had C1A. Pts with C1A had higher stage (ISS III 35% vs 26%; p < 0.01) and other HRM (27% vs 14%, p < 0.01). Common first line-therapies included bortezomib(V), lenalidomide(R) and dexamethasone (D) (35%), RD (20%) followed by VD(15%). Use of VRD was higher with C1A vs without (40% vs 33% respectively, p < 0.01). Median OS was 66.9 months for the entire cohort and was lower for pts with C1A vs without (median OS 46.6 vs 70.1 months; log rank p < 0.01). Multivariable Cox survival analysis showed that C1A was independently associated with worse OS (adjusted HR 1.64; 95% CI 1.23-2.19); p < 0.01). Other predictors of worse survival included older age, black ethnicity, higher ISS stage, poor performance status and HRM. Conclusions: In this large study of real-world practice, C1A was associated with inferior OS independent of other HRM, despite higher use of VRD. Future studies are needed to assess whether specific regimens improve outcomes for C1A compared to patients without HRM.

scholarly journals A real-world registry to evaluate HER2-directed therapy in Australian patients with metastatic breast cancer (MBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12515-e12515
Author(s):  
Margaret Lee ◽  
Sheau Wen Lok ◽  
Natalie Heather Turner ◽  
Daphne Day ◽  
Sally Greenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
De Novo ◽  
Performance Status ◽  
Metastatic Breast ◽  
Poor Performance ◽  
Poor Performance Status ◽  
First Line ◽  
Her2 Positive ◽  
Substantial Impact

e12515 Background: The management and outcomes of HER2 positive MBC have dramatically evolved with the introduction of HER2-targeted therapies. However, limited data regarding the uptake, impact and safety of these treatments in the real-world context, prompted us to initiate a comprehensive registry across multiple settings in Australia. Methods: We examined the multisite electronic registry TABITHA (Treatment of Advanced Breast Cancer in the HER2 positive Australian Patient) to capture clinical data of consecutive patients diagnosed with HER2 positive MBC between Jan 2016-Jan 2017. Patient demographics, use and outcomes of treatment were explored. Results: An initial cohort of 74 patients was identified, 28 (38%) with de novo metastatic and 46 (62%) with relapsed disease. The median age at presentation with MBC was 57 years (range 27-83), with main metastatic sites being bone (n = 41, 55%), major organs (n = 40, 54%), locoregional (N = 26, 35%) and central nervous system (n = 13, 18%). In total, 64 (86%) patients had received first-line HER2 therapy, including trastuzumab plus pertuzumab (n = 48, 75%), trastuzumab alone (n = 10, 16%) and trastuzumab-emtansine (n = 6, 9%). Ten patients had not received any HER2 therapy, of which 8 received best supportive care alone, 1 received endocrine therapy, and 1 received anti-resorptive therapy. The median age of non-HER2 treated patients was 61 (range 44-81) and 40% were ECOG 2+ compared to 25% of patients receiving HER2 therapy (p = NS). First-line HER2 therapy had been discontinued in 20/63 (32%) patients, due to progressive disease (n = 18, 90%) or toxicity (n = 2, 10%). Median time to progression was 12.7+ months (range 2.0-81.9+). Conclusions: Whilst trials of HER2 directed therapies have demonstrated a substantial impact on survival outcomes for MBC with modest toxicity, a proportion of HER2 positive patients in routine care may not receive these agents. Poor performance status contributes to non-HER2 therapy use, however data collection is ongoing and other potential drivers will be further examined. Where HER2 directed therapies are used, the preliminary data indicates good activity with the majority of patients still currently on treatment.

Predictors of hypomethylating agent discontinuation among patients with higher-risk myelodysplastic syndromes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7043-7043
Author(s):  
Amer Methqal Zeidan ◽  
Namita Joshi ◽  
Hrishikesh Kale ◽  
Wei-Jhih Wang ◽  
Shelby Corman ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Real World ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Poor Performance ◽  
Risk Groups ◽  
Refractory Anemia ◽  
Poor Performance Status ◽  
Related Factors

7043 Background: Real-world studies have shown that persistence with intravenous (IV) and subcutaneous (SC) hypomethylating agents (HMAs) among patients (pts) with higher-risk myelodysplastic syndromes (MDS) is poor, with over one-third of treated pts receiving <4 cycles or having a ≥90-day gap in therapy, despite recommendations for at least 4-6 cycles to elicit response in absence of progression/unacceptable toxicity. Survival outcomes have also been shown to be worse, and direct medical costs higher, among HMA non-persistent vs persistent pts. We explored factors associated with early discontinuation of HMA therapy in this population. Methods: This was a retrospective cohort study among pts from the 2010-2016 SEER-Medicare linked database with a diagnosis of refractory anemia with excess blasts (RAEB; a surrogate for higher-risk MDS) from 2011-2015. Included pts had to have received HMA therapy and have ≥12 months’ continuous follow-up after diagnosis. Discontinuation was defined as stopping HMA therapy before 4 cycles. Multivariable logistic regression was used to assess predictors of HMA discontinuation. Results: In total, 664 pts with RAEB and treated with HMAs were included. Overall, 193 (29%) discontinued before 4 cycles; of these, 91 (47%) discontinued after 1 cycle, 57 (30%) 2 cycles, and 45 (23%) 3 cycles. Compared with pts continuing for ≥4 cycles, pts discontinuing before 4 cycles were generally older and more likely to be single/separated/divorced/widowed, have more comorbidities, and have poor performance status (PS) (Table). These trends were most pronounced among pts discontinuing HMA therapy after only 1 cycle vs ≥4 cycles (Table). In multivariable analysis, age 71-75 vs ≥80 y (odds ratio [OR] 0.556, p=0.017) and poor PS (OR 1.585, p=0.019) remained significant predictors of HMA discontinuation. Among treatment-related factors, the most statistically significant association with HMA discontinuation was observed for GCSF use (OR 0.453, p<0.001). Number of pills/day was not a predictor of HMA discontinuation (OR 1.009, p=NS). Conclusions: In this real-world study, almost one-third of RAEB pts treated with IV/SC HMAs discontinued before 4 cycles, with almost half of these pts discontinuing after only 1 cycle. Predictors of HMA discontinuation included older age and poor PS. Novel approaches are needed to improve persistence with HMA therapy, particularly among these higher-risk groups.[Table: see text]

scholarly journals Generalizability of Landmark Clinical Trials in Diffuse Large B Cell Lymphoma to Real-World Patients: A Single-Centre Retrospective Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Marta Davidson ◽  
Alexandra Rice ◽  
Douglas A. Stewart ◽  
Carolyn Owen
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Real World ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
Novel Therapies ◽  
Alberta Cancer Registry

Background: Clinical trials are the gold standard by which therapies in oncology are evaluated and ultimately form the bases for approval of novel therapies. Stringent eligibility criteria limit the participation of many "real-world" patients and thus undermine the generalizability of trial results. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkin lymphoma (NHL) and is curable in the majority of patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The addition of rituximab to CHOP is the only clear advancement in DLBCL therapy in the last 20 years. Though a large minority of patients are not cured by R-CHOP, several subsequent novel therapies have failed to demonstrate benefit in Phase 3 clinical trials. We hypothesized that real world patient populations differ from clinical trial populations with trial eligibility excluding the poor-outcome patients who might benefit most from novel therapy. Methods: We performed a retrospective chart review of all patients 18 years of age or older who were registered within the Alberta Cancer Registry with a new diagnosis of pathology-confirmed DLBCL, between January 1, 2010 and December 31, 2011. Clinical characteristics were reviewed to assess patient eligibility to participate in 3 landmark clinical trials for DLBCL on the basis of inclusion and exclusion criteria defined by each study. The trials included Pfreundschuh, M. et al. (2006) and Coiffier, B. et al. (2002), which were assessed together as representing the landmark studies for rituximab added to CHOP, and the GOYA trial (2017) which evaluated obinutuzumab-CHOP vs R-CHOP. Categorical variables are presented as frequencies and percentages. Univariate probabilities of overall-survival were calculated by Kaplan-Meier method. Results: We identified 480 patients with a diagnosis of DLBCL within the Alberta Cancer Registry. A total of 390 patients were eligible for our study with 20 patients excluded for CNS lymphoma, 29 for unclassifiable B-cell lymphoma, 2 patients who died at the time of diagnosis, and 25 patients with previously treated indolent lymphoma. In addition, 14 patients were excluded for insufficient clinical data. Table 1 demonstrates the clinical characteristics of the population. Out of 390 patients, only 130 (33%) patients met inclusion for the rituximab studies and 134 (34%) for the GOYA study. Table 2 demonstrates the most common criteria leading to trial exclusion, including poor performance status, limited stage disease, inappropriate IPI, transformed lymphoma, history of second primary malignancy, and viral infections. Trial ineligible patients had significantly inferior overall survival compared to trial eligible patients (Figure1). Conclusions: The majority of real-world DLBCL patients are excluded from clinical trials and have inferior outcomes compared to trial eligible patients. The selection of patients with more favourable outcomes for clinical trials may contribute to failure to demonstrate a benefit of novel therapies. Broadening inclusion criteria to include patients with transformed disease and poor performance status could aid in improving the generalisability of DLBCL clinical trials. Disclosures Stewart: Gilead: Honoraria; Roche: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Teva: Honoraria; Sandoz: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria. Owen:AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria.

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