scholarly journals Postoperative Concurrent Chemoradiotherapy Plus Apatinib for First-line Treatment of Patients with Malignant Glioma: From One Single Research Institute

2021 ◽  
Author(s):  
Zhichao FU ◽  
Xiaoyan Li ◽  
Wenmin YING ◽  
lvjuan CAI ◽  
Guo LI ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Concurrent Chemoradiotherapy ◽  
Proportional Hazards ◽  
Statistical Significance ◽  
Group Versus ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Cox Proportional Hazards ◽  
Control Group ◽  
Retrospective Case

Abstract Objective: To explore the effectiveness and safety of apatinib in patients with malignant glioma. Methods: This is a retrospective case-control study in a single center. Patients with new postoperative pathological diagnosis of malignant glioma (WHO Ⅲ~Ⅳ) were selected. Enrolled patients received concurrent chemoradiotherapy (60Gy/30f/6w; TMZ75mg/m2,po,d1-d42)combined with or without apatinib (250mg, po, d1-d42,qd), then maintain 6 cycles(28 days a cycle)of TMZ chemotherapy(200mg/m2, d1-d5) .The primary endpoints were progression free survival (PFS) and the grade of peritumoral brain edema (PTBE) evaluated by edema index(EI). The secondary endpoint was overall survival(OS). Hazard ratios of PFS and OS were compared between trials in a Cox proportional hazards model.Results: 48 patients (24 in apatinib group and 24 in control group) were enrolled in this study. The results elucidated that the mPFS of the apatinib group was longer than control group, but the difference was not statistically significant(9.63 vs. 7.33 months; P=0.073).As for mOS, the results of two groups were almost similar.(15.47 vs. 14.70 months, P=0.612). Cox multivariate regression model revealed that Apatinib was not a prognostic factor for PFS and OS (P>0.05). Multivariate analysis showed that tumor grade was an important risk factor for PFS and OS.The grade of PTBE was improved in 15 of 23 patients (65.2%) in apatinib group versus 6 of 24 (25%) in control group. There was no grade 3 or 4 adverse events and serious adverse events.Conclusion: Apatinib group can improve mPFS by 2.3 months in patients with malignant glioma,but there was no statistical significance (P>0.05).The results also indicated that apatinib conferred a significant beneficial effect on PTBE improvement. All occurred adverse reactions were moderate and controllable.

Postoperative concurrent chemoradiotherapy plus apatinib in patients with malignant glioma: From one single research institute.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14049-e14049
Author(s):  
Zhichao Fu
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Malignant Glioma ◽  
Concurrent Chemoradiotherapy ◽  
Statistical Significance ◽  
Antiangiogenic Therapy ◽  
Group Versus ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Control Group

e14049 Background: Antiangiogenic therapy is a choice for the treatment of malignant glioma patients. Vascular endothelial growth factor receptors (VEGFRs) inhibitors block the new formation around the tumor and cut down the supply of oxygen, nutrients and metabolic waste, so that the tumor is hard to proliferate and metastases.Objective To explore the effectiveness and safety of apatinib in patients with malignant glioma. Methods: This is a retrospective and prospective case-control study conducted in a single center. Patients with new postoperative pathological diagnosis of malignant glioma (WHO IIĨIV) were selected. Enrolled patients received concurrent chemoradiotherapy (radiotherapy60Gy/30f/6w; TMZ75mg/m2,po,d1-d42) combined with or without apatinib (250mg, po, d1-d42,qd), then maintain 6 cycles(28 days a cycle)of TMZ chemotherapy(200mg/m2, d1-d5) .The primary endpoints were investigator-assessed progression free survival (PFS) and the grade of peritumoral brain edema (PTBE) evaluated by edema index(EI). The secondary endpoint was investigator-observed overall survival. Hazard ratios of PFS and OS were compared between trials in a Cox proportional hazards model. Results: Between October 2017 and March 2019, 47 patients (23 in apatinib group and 24 in control group) were enrolled in this study.The median age was 47 years in apatinib group (range from 19 to 73 years) versus 48 years in control group(range from 24 to 68 years). The results elucidated that the median PFS of the apatinib group was longer than that of the control group, but the difference was not statistically significant.(9.26 months vs. 6.69 months; hazard ratio, 0.65; 95% confidence interval [CI], 0.31 to 1.25; P=0.1906).As for median overall survival, the results of two groups were almost similar.(14.42 months vs. 14.36 months; hazard ratio, 0.74; 95%CI, 0.36 to 1.52; P=0.4036). Cox multivariate regression model revealed that apatinib was not a prognostic factor for PFS and OS (P>0.05). As of the statistical date, there were 7 patients with stable disease (SD), 16 patients with progressive disease (PD) and 13 patients with death in the apatinib group; whereas in the control group, the condition of 3 patients remained stable, the other 21 patients had progressed, with 19 unfortunate deaths. The grade of PTBE was improved in 15 of 23 patients (65.2%, 5/23 patients used corticosteroids) in apatinib group versus 6 of 24 (25%, 14/24 patients used corticosteroids) in control group. There was no grade 3 or 4 adverse events and serious adverse events. Conclusions: Compared with control group, apatinib group still improved mPFS by 2.57 months in patients with malignant glioma, but there was no statistical significance (P>0.05).The results also indicated that apatinib conferred a significant beneficial effect on PTBE improvement. All occurred adverse reactions were moderate and controllable. Clinical trial information: NCT03567135.

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

Correlation of DPC4 status with outcomes in pancreatic adenocarcinoma patients receiving adjuvant chemoradiation.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 168-168
Author(s):  
J. M. Herman ◽  
C. C. Hsu ◽  
E. K. Fishman ◽  
R. H. Hruban ◽  
S. H. Lin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Local Recurrence ◽  
Proportional Hazards ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Distant Recurrence ◽  
Cox Proportional Hazards ◽  
Liver Recurrence ◽  
Patterns Of Recurrence

168 Background: In an autopsy series of patients with advanced pancreatic cancer (PCA), loss of DPC4 was highly correlated with disseminated metastasis. The purpose of this study was to determine if DPC4 gene status predicts for survival and patterns of recurrence following adjuvant (adj) chemoradiation (CRT). Methods: 101 patients who underwent surgery followed by adjuvant 5-FU or gemcitabine-based CRT were studied. Imaging studies were reviewed to assess patterns of recurrence and tumor tissue obtained to determine DPC4 immunolabeling status. DPC4 status was graded as intact or lost/mutated. Kaplan-Meier estimates were used to compute survival and Cox proportional hazards were used to compare risk factors. Results: Median overall (mOS) and progression-free survival (PFS) was 22.6 mos (95% CI 18.8 to 31.6) and 14.0 mos (95% CI 11.5 to 18.4). The mOS and 1-yr OS for patients with DPC4 intact vs. lost status was 21.9 mos (95% CI 16.8-32.4) and 78.4% vs. 22.6 mos (95% CI 18.4-32.6) and 78.2%, respectively (HR: 1.05, p=0.82). After adjusting for node, margin status, tumor grade, tumor size, and age, DPC4 status did not predict for mOS (RR 1.04, 95% CI: 0.62-1.74, p=0.89). Time to first progression at any site for PCA with DPC4 intact vs. lost status was 13.8 vs. 14.0 mos (p=0.79). Local recurrence was more common in PCA with DPC4 loss than with intact status (34.4% vs. 13.7%, p=0.012). There was no difference in the rates of distant recurrence in PCA with intact vs. loss of DPC4 expression (62.8% vs. 55.7%, p=0.45); however, DPC4 loss was more commonly associated with liver recurrence (27.9% vs. 19.6%, p=0.31). Conclusions: In pancreatic cancer patients receiving adj CRT, loss of DPC4 labeling in their resected PCA indicates a greater likelihood of developing local recurrence despite having received adj CRT. Efforts to improve loco-regional control are therefore needed for these patients following surgery and adj CRT. No significant financial relationships to disclose.

scholarly journals Outcomes After Proton Therapy Reirradiation for Malignant Glioma: Prospective Analysis of Over 100 Patients from the Proton Collaborative Group

2021 ◽  
Author(s):  
Robert H Press ◽  
Shaakir Hasan ◽  
J Isabelle Choi ◽  
Arpit M Chhabra ◽  
Lia M Halasz ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Proton Therapy ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Collaborative Group ◽  
Time Interval ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Purpose: The optimal salvage treatment for malignant glioma after prior radiotherapy (RT) is not well established. Proton therapy (PT) is an attractive treatment modality for reirradiation (ReRT) of recurrent disease; however, data are limited.Methods: The prospective, multi-institutional Proton Collaborative Group (PCG) registry was queried for patients with malignant glioma who previously received RT and underwent PT-ReRT between 7/2011-10/2018. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis. Results: 109 consecutive patients were identified. Median follow-up was 11.2 months and median time interval (TI) from prior RT (median 59.3 Gy) to PT-ReRT (median 49.6 Gy) was 45.7 months. Primary histology was glioblastoma (n=62), oligodendroglioma (n=26), and astrocytoma (n=20). Median PFS and OS was 6.1 and 11.1 months, respectively. On UVA, improved PFS was associated with oligodendroglioma (HR 0.39) and astrocytoma (HR 0.55) histologies, WHO Grade III (HR 0.36), TI (HR 0.989), surgical resection (HR 0.39), and PT-ReRT dose ≥50 Gy (HR 0.59) (all p<0.03), while improved OS was associated with oligodendroglioma histology (HR 0.35), WHO grade III (HR 0.33), ECOG 0 (HR 0.47), TI (HR 0.985), and PT-ReRT dose ≥50 Gy (HR 0.58) (all p<0.04). Late Grade 3 toxicities occurred in 5.6% of patients with no attributable acute or late Grade 4-5 events.Conclusion: In the largest series of glioma PT-ReRT reported to date, retreatment appears well tolerated with acceptable outcomes and favorable toxicities compared to photon historical controls. Dose escalation achievable with PT may improve outcomes for well-selected patients.

Bevacizumab beyond progression: Impact of subsequent bevacizumab retreatment in patients with ovarian, fallopian tube, and peritoneal cancer after progression.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5557-5557 ◽  
Author(s):  
Rebecca Ann Previs ◽  
Daniel Spinosa ◽  
Bryan M. Fellman ◽  
Amelia Lorenzo ◽  
Isabelle Mulder ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Proportional Hazards ◽  
Brca Mutation ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Clinic Visit ◽  
Cox Proportional Hazards ◽  
Peritoneal Cancer ◽  
Bevacizumab Treatment ◽  
Significant Difference

5557 Background: The Food and Drug Administration approved the use of bevacizumab for treatment of recurrent epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) in combination with chemotherapy. This study evaluates whether patients immediately retreated with bevacizumab derive benefit after progressing on a bevacizumab-containing regimen. Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). All patient retreated with bevacizumab had stable or progressive disease on prior bevacizumab containing regimen. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan and Meier product-limit estimator and modeled via Cox proportional hazards regression. PFS was measured from the date of first bevacizumab treatment to the date of first progression, date of death or date of last clinic visit. OS was measured from the date of first bevacizumab treatment after progression to the date of death or date of last contact/clinic visit. Statistical significance was defined at the 0.05 level. Results: 275 patients received bevacizumab, of which 226 were evaluable; 102 received sequential treatment with bevacizumab and 124 received a bevacizumab containing regimen followed by a non-bevacizumab containing regimen at the time of progression. There was no significant difference between tumor grade, stage, or BRCA mutation. Median follow-up for all subjects was 17 months (range: 1.2-138.2 months). Median PFS was 10.21 months (95%CI: 8.05 - 11.79) and median OS was 22.14 months (95%CI: 17.1 – 27.4). Median PFS for patients who received bevacizumab without retreatment was 5.1 months (95%CI: 4.3 – 6.3) and 17.6 months (95%CI: 14.3 – 21.3) for patients who received sequential bevacizumab retreatment (p < 0.001). Median OS for patients who received bevacizumab without retreatment was 12.9 months (95%CI: 9.3 – 16.7) and 30.1 months (95%CI: 26.1 – 35.4) for patients who received sequential bevacizumab retreatment (p < 0.001). Conclusions: Our study shows OC patients treated with bevacizumab-containing regimens sequentially at the time of progression have significantly prolonged survival outcomes compared to those patients who received no re-treatment with bevacizumab.

Risk stratification based on a prognostic factor index among patients with HR+, HER2- MBC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12516-e12516
Author(s):  
Gregory A. Vidal ◽  
Gebra Cuyun Carter ◽  
Adrienne Gilligan ◽  
Kim Saverno ◽  
Yajun Emily Zhu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
De Novo ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Cox Proportional Hazards ◽  
First Line ◽  
The Impact

e12516 Background: Patient and tumor characteristics, such as tumor grade (TG), site of metastases, hormone receptor status, and endocrine resistance, affect the prognosis for patients (pts) with HR+, HER2- metastatic breast cancer (MBC). This study explored the impact of multiple clinical prognostic factors on pt overall survival (OS) and real-world progression-free survival (rwPFS). Methods: This retrospective study used electronic health record (EHR) data of US pts from a network of community oncology practices maintained in the Vector Oncology Data Warehouse from 1/1/2008 to 4/30/2017. Eligibility included HR+, HER2- MBC diagnosis in 2008 or later and prior systemic therapy for MBC. An index variable was created to assess the effect of multiple clinical prognostic factors collectively, including liver metastases (LM), primary endocrine resistance (PER) (Cardoso F et al. 2018), negative progesterone receptor (PR-) status, and high TG. Pts were grouped based on the number of prognostic factors present at MBC diagnosis: 0, 1, and 2+. Differences in rwPFS and OS from start of first line therapy were evaluated by Kaplan-Meier method and multivariable Cox proportional hazards regression. Results: Eligible pts (n=378) had a mean age of 60.3 years. Among these 57.1% were white, 36.5% were de novo metastatic, 22% had LM, 27.2% had high TG, and 27.1% were PR- at baseline. Among all pts, 170 (45%) had received endocrine therapy as first-line treatment, followed by chemotherapy (28%), CDK4 & 6 inhibitor (17%), or other anti-cancer treatment (9%). After adjustment, rwPFS and OS were significantly (p<.05) shorter in pts with 1 and 2+ clinical prognostic factors compared to pts with none (Table). Conclusions: Among pts with HR+, HER2- MBC, these data demonstrate the heterogeneity in pt survival outcomes depending on the presence and number of prognostic factors. Further research should explore the collective importance of these prognostic factors in treatment decisions. [Table: see text]

The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Oncology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Oded Jacobi ◽  
Yosef Landman ◽  
Daniel Reinhorn ◽  
Oded Icht ◽  
Michal Sternschuss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Negative Relationship ◽  
Progression Free Survival ◽  
Significant Negative Correlation ◽  
Cox Proportional Hazards ◽  
Diabetic Patients

<b><i>Introduction:</i></b> Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. <b><i>Methods:</i></b> All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, <i>t</i> tests, and χ<sup>2</sup> tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. <b><i>Results:</i></b> Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], <i>p</i> = 0.011, and HR 1.5 [1.08–2.08], <i>p</i> = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], <i>p</i> = 0.79, and HR 1.29 [0.69–2.39], <i>p</i> = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. <b><i>Conclusion:</i></b> Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

scholarly journals Epilepsy as a Comorbidity in Polymyositis and Dermatomyositis—A Cross-Sectional Study

2021 ◽  
Vol 18 (8) ◽  
pp. 3983
Author(s):  
Ella Nissan ◽  
Abdulla Watad ◽  
Arnon D. Cohen ◽  
Kassem Sharif ◽  
Johnatan Nissan ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cross Sectional Study ◽  
Cox Proportional Hazards ◽  
Categorical Variables ◽  
Rank Test ◽  
Control Group ◽  
Multivariable Logistic Regression Analysis ◽  
Positive Trend ◽  
Continuous Variables ◽  
Cross Sectional

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case–control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student’s t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan–Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.

scholarly journals The incidence of mental disorder increases after hip fracture in older people: a nationwide cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ling-Yin Kuo ◽  
Po-Ting Hsu ◽  
Wen-Tien Wu ◽  
Ru-Ping Lee ◽  
Jen-Hung Wang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hip Fracture ◽  
Geriatric Patients ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Control Group ◽  
Research Database ◽  
Fracture Group ◽  
Related Risk ◽  
And Control

Abstract Background People living with dementia seem to be more likely to experience delirium following hip fracture. The association between mental disorders (MD) and hip fracture remains controversial. We conducted a nationwide study to examine the prevalence of MD in geriatric patients with hip fractures undergoing surgery and conducted a related risk factor analysis. Material and methods This retrospective cohort study used data from Taiwan’s National Health Insurance Research Database between 2000 and 2012 and focused on people who were older than 60 years. Patients with hip fracture undergoing surgical intervention and without hip fracture were matched at a ratio of 1:1 for age, sex, comorbidities, and index year. The incidence and hazard ratios of age, sex, and multiple comorbidities related to MD and its subgroups were calculated using Cox proportional hazards regression models. Results A total of 1408 patients in the hip fracture group and a total of 1408 patients in the control group (no fracture) were included. The overall incidence of MD for the hip fracture and control groups per 100 person-years were 0.8 and 0.5, respectively. Among MD, the incidences of transient MD, depression, and dementia were significantly higher in the hip fracture group than in the control group. Conclusions The prevalence of newly developed MD, especially transient MD, depression, and dementia, was higher in the geriatric patients with hip fracture undergoing surgery than that in the control group. Prompt and aggressive prevention protocols and persistent follow-up of MD development is highly necessary in this aged society.

Differential response rates in early-phase cancer clinical trials (EPCCT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3133-3133
Author(s):  
Rozana Abdul Rahman ◽  
Neethu Billy Graham Mariam ◽  
Hitesh Mistry ◽  
Sreeja Aruketty ◽  
Matt Church ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Rates ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Sustained Response ◽  
Phase Ii Trials ◽  
Significant Difference

3133 Background: The primary objective of EPCCT (phase I and non-randomised phase II trials) is to determine the safety and tolerability of new therapeutic agents. Response rates (RR) in these trials have typically been reported at around 10-15%. Increasingly RR and survival outcomes are now investigated in EPCCT as primary or secondary objectives. Methods: Retrospective data analysis was performed on patients (pts) enrolled onto an EPCCT between January 2018 and December 2019 at The Christie NHS Foundation Trust, UK. Data on demographics, prior systemic treatment, sites of disease, performance status, comorbidities, types of therapy, RR, progression free survival (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable models. Objective response rate (ORR) was defined as the proportion of pts with complete response (CR) and partial response (PR). Duration of response (DOR) was from initial response to progressive disease (PD). Disease control rate (DCR) was defined as CR+PR+ stable disease (SD). Results: A total of 247 pts were treated across 46 EPCCTs. Median age 61 years; 57% female. Sixty-six percent of pts had ≥2 lines of treatment and the majority were ECOG PS 0/1 (98%). Eighty-one percent of pts had ≥2 sites of metastatic disease, and 13 major tumour types were included. Monotherapy trials (159 pts) were predominantly targeted therapies (TT; 60%), or immunotherapies (IO; 20%). Combination therapy trials (88 pts) were TT-based (68%) or IO-based (32%). Data for RR analyses was available for 231 pts. ORR across all trials was 15% (CR 2%) and DCR was 63%. The median DOR was 8.3 months (mos) (95% CI: 7.0 – 9.7) with 28% of pts responding for >6 mos and 7% for >12 mos. ORR in pooled IO treated pts was 27%, DCR was 65% with sustained response >6 mos seen in 37% of these pts. ORR in pooled TT treated pts was 9.4%, DCR was 60% and sustained response > 6 mos seen in 25% of pts. ORR for IO v TT treated pts was significantly different, p=0.007 (pearson chi square), but no significant difference was seen for DCR. Median PFS for all patients was 5.0 mos (95% CI: 4.1 – 6.0) and OS was 10.4 mos (95% CI: 8.4 – 13.0). OS for those with a PR is not reached (HR for PR v PD, 0.006 (95% CI: 0.002 – 0.18). Pts with SD appear to have significantly better OS compared to those with PD (14.6 v 4.2 mos, HR 0.2 (95% CI: 0.1 – 0.3). Multivariable Cox proportional hazards analysis for OS was significant for male gender (HR 1.9, p=0.002), presence of liver metastasis (HR 2.0, p=0.001), low Hb (HR 0.8, p=0.03) and log (LDH) (HR 1.9, p<0.001). Conclusions: Two-thirds of pts enrolled on EPCCTs benefitted in terms of DCR with significant OS improvement in those with PR and SD. Higher ORR were seen in pts receiving IO-based treatments however DCR was similar in IO and TT pts. Gender, presence of liver metastases, Hb count and LDH level contributed significantly to survival differences.

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