Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

2022 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K Kavouridis ◽  
Timothy R Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

scholarly journals Short-term outcomes associated with temozolomide vs. PCV chemotherapy for 1p/19q-codeleted WHO grade III anaplastic oligodendrogliomas: a national evaluation

2020 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K. Kavouridis ◽  
Timothy R. Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Long Term Results ◽  
National Database ◽  
Newly Diagnosed ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Pcv Chemotherapy ◽  
Grade Iii

AbstractPURPOSEThe optimal chemotherapy regimen between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV) remains uncertain for newly-diagnosed anaplastic oligodendroglioma (AO). We therefore addressed this question using a national database.METHODSPatients newly-diagnosed with 1p/19q-codeleted W.H.O. grade III AO between 2010-2016 were identified from the National Cancer Database. Predictors of receiving first-line single-agent TMZ vs. multi-agent PCV were assessed by multivariable logistic regression. Overall survival (OS) was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression.RESULTS1,360 AO patients were identified: 74.5% (n=1,013) treated with TMZ, 9.6% (n=131) with PCV, and 15.9% (n=216) with no chemotherapy in the first-line setting. In multivariable logistic analysis, PCV utilization increased from 2010 to 2016 (OR=1.38/year, 95%CI: 1.22-1.56, p<0.001) and was less commonly utilized in privately insured patients (OR=0.38 vs. uninsured, 95%CI: 0.15-0.97, p=0.04). In survival analyses (33.1% reached endpoint), there was no difference in unadjusted OS between TMZ (5yr-OS 60.1%, 95%CI: 55.9-64.1) and PCV (5yr-OS 61.1%, 95%CI: 45.6-73.5; p=0.42). There remained no OS difference between TMZ and PCV in the 75.9% (n=1,032) of AO patients that also received radiotherapy (p=0.51), in the Cox regression analysis adjusted by age, extent of resection, and radiotherapy (TMZ vs. PCV HR=1.31, 95%CI: 0.83-2.08, p=0.24), and in subgroup analyses that incorporate KPS or MGMT status.CONCLUSIONSIn a national database of AOs managed in the ‘real-world’ setting, there is no difference in the short-term mortality between first-line TMZ and PCV chemotherapy. These findings provide preliminary data while we await the long-term results from the CODEL trial.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

scholarly journals Development of An Inflammatory Response-Related Gene Signature To Predict Prognosis and Immunotherapy Response For Patients With Glioma

2021 ◽  
Author(s):  
Zhen Zhao ◽  
Jianglin Zheng ◽  
Yi Zhang ◽  
Xiaobing Jiang ◽  
Chuansheng Nie ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Low Risk ◽  
Normal Brain ◽  
Related Gene ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract Inflammatory response plays a crucial role in the development and progression of gliomas. However, the prognostic value of inflammatory response-related genes has never been comprehensively investigated for glioma. In this study, we identified 39 differentially expressed genes (DEGs) between glioma and normal brain tissue samples, of which 31 inflammatory response-related genes are related to the prognosis of glioma., The 8 optimal inflammatory response-related genes were selected to construct prognostic inflammatory response-related gene signature (IRGS) through the least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis. The effectiveness of the IRGS was verified in the training (TCGA) and validation (CGGA-693 CGGA-325 and Rembrandt) cohorts. The Kaplan-Meier curve revealed a significant difference in the OS between the high- and low-risk groups. The receiver operating characteristic curve (ROC) shows the powerful predictive ability of IRGS. Meanwhile, a nomogram with better accuracy was established to predict overall survival (OS) based on the independent prognostic factors (IRGS, age, WHO grade, and 1p19q codeletion). In addition, patients in the high-risk group had higher immune, stroma, and ESTIMATE scores, lower tumor purity, higher infiltration of immunosuppressive cells, higher expression of immune checkpoints, higher expression of TIDE and Exclusion, and lower expression of MSI Expe Sig. Thus, the patients in the low-risk group had significantly higher respond rate of immune checkpoint inhibitors (ICIs). A novel prognostic signature incorporated 8 inflammatory response-related genes was associated with the prognosis, immune landscape and the immunotherapy response in patients with gliomas. Thus, the signature can be suitable for future clinical application to predict the prognosis of patients with glioma.

scholarly journals Clinical Implications of Girdin Protein Expression in Glioma

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Liwei Zhao ◽  
Shuyin Ma ◽  
Qing Liu ◽  
Peng Liang
Keyword(s):  
Protein Expression ◽  
Cox Regression ◽  
Strong Predictor ◽  
Extent Of Resection ◽  
Biological Behavior ◽  
Low Grade ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
The Relationship ◽  
Expression Status

Objective. To investigate the expression status of Girdin in glioma and the relationship between Girdin expression and the biological behavior of glioma.Materials and methods. The expression status of Girdin in glioma from 560 cases was evaluated by RT-PCR, Western Blot and immunohistochemistry. The relationship between Girdin expression and clinic-pathological parameters as well as prognosis was also studied.Results. The expression of Girdin in high grade glioma was significantly higher than low grade glioma. After universal analysis, the expression of Girdin protein is closely related to KPS score, extent of resection, Ki67 and WHO grade, but it was not related to sex and age. Finally, extent of resection, Ki67 and WHO grade were indentified to be related to the Girdin protein expression in logistic regression. Interestingly, we found that the expression of Girdin is significantly related to the distant metastasis of glioma. After COX regression analysis, KPS score, Extent of resection, Ki67, WHO grade as well as Girdin were observed to be independent prognostic factors.Conclusions. Girdin is differential expressed in the glioma patients and closely related to the biological behavior of Glioma. Finally, Girdin was found to be a strong predictor for the post-operative prognosis.

scholarly journals HOUT-19. THE SHORT-TERM OVERALL SURVIVAL ASSOCIATED WITH SINGLE- VS. MULTI-AGENT CHEMOTHERAPEUTIC REGIMENS FOR 1p/19q-CODELETED WHO GRADE III ANAPLASTIC OLIGODENDROGLIOMAS: A NATIONAL EVALUATION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi116-vi116
Author(s):  
Mehdi Touat ◽  
Maya Harary ◽  
Vasileios Kavouridis ◽  
Timothy Smith ◽  
Bryan Iorgulescu
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Cox Regression ◽  
Single Agent ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Multi Agent ◽  
Who Grade Iii ◽  
Grade Iii

Abstract INTRODUCTION Although diffuse gliomas of oligodendrocytic lineage demonstrate chemosensitivity, the survival outcomes associated with single- (i.e. temozolomide; TMZ) or multi-agent (i.e. PCV) chemotherapy regimens remain uncertain for anaplastic oligodendrogliomas (AO). METHODS Patients presenting between 2010–2016 with 1p/19q-codeleted WHO grade III AO were identified by ICD-O3 and site-specific factors from the National Cancer Database, which comprises >70% of cancers newly-diagnosed in the U.S. Predictors of receiving first-line single- vs. multi-agent chemotherapy were assessed by multivariable logistic regression. Overall survival (OS) was estimated by Kaplan-Meyer approaches and evaluated by multivariable Cox regression. RESULTS There were 952 patients with 1p/19q-codeleted WHO grade III AO and complete first-line chemotherapy data, with: 13.9% (n=132) no-, 75.0% (n=714) single-, and 11.1% (n=106) multi-agent chemotherapy. In logistic regression of chemotherapy-treated AOs, more recent diagnosis was associated with higher multi-agent (OR=1.48/year, 95%CI=1.25–1.74, p< 0.001) rates; otherwise there were no associations of single- vs. multi-agent chemotherapy with patient sex, age-at-diagnosis, race, insurance status (reference=privately insured), comorbidity index, tumor greatest dimension, tumor location (reference=frontal lobe) or crossing of midline, nor with radiotherapy or EOR (all p >0.05). Multi-agent usage rose from 3.6% in 2010 to 24.3% in 2016. Median follow-up was 34.9mos (IQR=18.8–54.8). The unadjusted 5yr-OS rate was 57.4% (95%CI=43.5–69.1) for no chemotherapy, 72.1% (95%CI=67.1–76.5) for single-agent, and 77.5% (95%CI=59.9–88.1) for multi-agent. Cox regression (adjusting for the above variables of radiotherapy and EOR, patient demographics, and tumor characteristics) demonstrated no significant OS difference between single- and multi-agent (HR=0.91, 95%CI=0.38–2.15, p=0.82) chemotherapy. CONCLUSIONS In a national database of AOs managed in the ‘real-world’ setting, there is increasing utilization of multi-agent (i.e. PCV) chemotherapy; but no significant difference in risk-adjusted short-term mortality (i.e. ~3-5yrs after diagnosis) between first-line multi- and single-agent (i.e. TMZ) chemotherapy. These findings provide preliminary data while we await the long-term PFS and OS results from the CODEL trial.

Infection Complications in 476 Patients with Newly Diagnosed Multiple Myeloma Treated with Lenalidomide or Bortezomib Combinations

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5365-5365 ◽  
Author(s):  
Massimo Offidani ◽  
Laura Corvatta ◽  
Sara Bringhen ◽  
Silvia Gentili ◽  
Francesca Gay ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Febrile Neutropenia ◽  
Antibiotic Prophylaxis ◽  
Cox Regression ◽  
Autologous Transplantation ◽  
Newly Diagnosed ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract Introduction. Multiple myeloma (MM) represents a population with an increased risk of developing infection up to 10-fold if compared with controls. Moreover, patients treated with new-drugs are at higher risk of infections compared with those treated previously (Blimark C. et al. Haematologica 2015). Grade 3-4 non-hematological toxicity, particularly cardiac and infection complications, are associated with shorter OS in patients with MM (Bringhen S. et al. Haematologica 2013) whereas thrombosis did not. Anyway, guidelines to prevent thrombosis are available but there are not as regard infections although they would be advisable since infections still represent one of leading non-hematological adverse event in any protocols. Methods. Newly diagnosed MM patients included in 2 prospective trials (VMP vs VMPT, Palumbo et al. JCO 2014; MPR vs MEL-200, Palumbo et al. NEJM 2014) were studied with the aim to assess probability, type, severity, timing and factors predictive of grade 3-5 infectious complications (according to CTCAE version 4.03) occurred during the first years of treatment with these bortezomib or lenalidomide combinations. Patients who underwent autologous transplantation were censored at the time of transplant. Infections were classified according to Immunocompromised Host Society criteria (J Infect Dis, 1990). All patients received thrimethoprim-sulphamethoxazole prophylaxis and patients treated with bortezomib received anti-viral prophylaxis, yet. Results. Four-hundred and seventy-six patients were analyzed. Median age was 66 years (range 36-85). Karnofsky performance status (KPS) was < 70 in 115 patients (24%), 106 (22%) had IgA heavy chain myeloma, 106 (22%) had ISS stage 3, 14 (3%) had renal insufficiency and 103/343 evaluated (30%) had unfavorable cytogenetic. Bortezomib combinations was administered to 257 patients (54%; 152 VMP, 105 VMPT) whilst 219 received lenalidomide combinations as induction-consolidation therapy (46%; 132 Rd, 87 MPR). One-hundred and fifty-eight febrile episodes (33.2%) were identified within the study population. Grade (G) 3-5 infections occurred in 53 patients (11%; G3=45, G4=7, G5=2). Out of these latter, 29 (55%) infections were clinically documented (pneumonia=22, soft tissue=5, gastrointestinal=2), 8 (15%) were microbiologically document (bacterial=7, viral=1) and 17(30%) were FUO (febrile neutropenia=11, sepsis=6). Pneumonia was the prevalent type of infection during treatment with Rd, VMP or VMPT whilst most febrile neutropenia or sepsis occurred during MPR treatment. Overall, probability of grade 3-5 infection was 13% at 12 months. However, the probability of infection reaching a plateau at 10-11% at 4 months in patients treated with Rd, VMP or VMPT whereas there was a second peak of infection at 35% probability at 12 months in patients treated with Rd followed by MPR consolidation (Fig. 1). Stepwise Cox regression analysis showed that KPS<70 (HR: 2.4; CI95%: 1.3-4.2; p=0.003), ISS stage 3 (HR: 2.1; CI95%: 1.2-3.7; p=0.013) and MPR regimen (HR: 2.1; CI95%: 1.2-3.8; p=0.017) were independently associated with increased risk of infection whereas age> 65 years, male sex, IgA myeloma type, renal failure, presence of plasmocytoma, unfavorable cytogenetic, bone marrow plasma cells > 60% and new agent used in induction (bortezomib or lenalidomide) were not. No significant difference in OS was found between patients who have had or not an infection (59 vs 71 months; p=0.333). Conclusions. This study suggests that, in patients with newly diagnosed MM treated with bortezomib or lenalidomide combinations, infections are a frequent cause of morbidity but not of mortality. Infections, mainly pneumonia, usually occurred in the first 4 months; however, when MPR was used as consolidation after Rd, the risk of unusual and severe infections continues all time long. Besides anti-PJ and anti-VZV prophylaxis, patients with poor KPS, with high tumor burden and who underwent MPR regimen, should receive antibiotic prophylaxis and they may be the ideal candidates to be included in a prospective, randomized study regarding antibiotic prophylaxis to prevent severe bacterial infections. Figure 1. Figure 1. Disclosures Offidani: Celgene, Janssen: Honoraria. Off Label Use: Lenalidomide. Corvatta:Celgene, Janssen: Honoraria. Bringhen:Onyx: Consultancy; Janssen-Cilag, Celgene, Novartis: Honoraria; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees. Gentili:Celgene, Janssen: Honoraria. Gay:Celgene, Janssen: Honoraria. Boccadoro:Celgene, Janssen: Consultancy, Honoraria. Palumbo:Celgene, Janssen: Consultancy, Honoraria, Research Funding.

Cisplatin versus carboplatin-based chemotherapy in inoperable or recurrent urothelial carcinoma: A retrospective analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14558-14558
Author(s):  
A. Bamias ◽  
E. Kastritis ◽  
G. Bozas ◽  
V. Koutsoukou ◽  
N. Antoniou ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Cox Regression ◽  
Distant Metastases ◽  
First Line ◽  
Cox Regression Analysis ◽  
The Poor ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Poor Tolerance

14558 Background: Cisplatin-based chemotherapy represents the standard for patients with inoperable or recurrent urothelial carcinoma. Carboplatin-based chemotherapy is reserved for not-fit-for-cisplatin patients. Recent data suggest that carboplatin-based chemotherapy may be effective in fit-for-cisplatin patients. We examined the differences in the outcome according to the compound used as first-line treatment. Methods: We selected patients who received first-line combination chemotherapy based on cisplatin or carboplatin. The major end point was survival. Survival curves were estimated with the Kaplan-Meier method, while cox regression analysis was used for multivariate models. Results: 445 patients, treated with cisplatin (330) or carboplatin (115)-based chemotherapy were included in this analysis. After a median follow-up of 52 months, there was no significant difference in survival between the two treatment groups (Table). Subgroup analyses according to PS, distant metastases, Hb, weight loss, showed that the use of cisplatin was independently associated with improved survival only in the PS 2,3 subgroup (see Table). When patients were stratified according to the Bajorin prognostic criteria (PS 0,1 vs. 2,3 and/or distant metastases yes vs. no; J Clin Oncol 1999, 17: 3173), again cisplatin-based chemotherapy was associated with a trend towards improved outcome only in the worst prognostic group (Table). Conclusions: Carboplatin-based chemotherapy may be equally effective to cisplatin-based treatment in patients with inoperable or recurrent urothelial cancer and no or one adverse factors. Cisplatin-based treatment may be beneficial in patients with poor prognosis. Nevertheless, the clinical relevance of this superiority is limited due to the poor outcome and the poor tolerance of cisplatin-based combination chemotherapy in this group of patients. (see Table) Median survival (95% CI) after first-line chemotherapy for advanced urothelial carcinoma. [Table: see text] No significant financial relationships to disclose.

Phase III study of standard triweekly versus dose-dense biweekly capecitabine (C) + oxaliplatin (O) + bevacizumab (B) as first-line treatment for metastatic colorectal cancer (mCRC): XELOX-A-DVS (dense versus standard): Interim analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4078-4078
Author(s):  
H. Hurwitz ◽  
Y. Z. Patt ◽  
D. Henry ◽  
L. Garbo ◽  
E. P. Mitchell ◽  
...  
Keyword(s):  
Cox Regression ◽  
Objective Response ◽  
Hazard Ratio ◽  
Statistical Testing ◽  
Phase Iii ◽  
First Line ◽  
Open Label ◽  
Cox Regression Analysis ◽  
Grade 3 ◽  
Dose Dense

4078 Background: Every 3 week (Q3W) COB has been shown to be highly active and non-inferior to FOLFOX+B in first-line mCRC. Phase II data suggest that dose-dense every 2 week (Q2W) COB may be significantly more active and better tolerated than Q3W COB. Methods: XELOXA-DVS was a phase III, open-label study of 435 patients with chemonaive mCRC who met standard eligibility criteria. Patients were randomized to Q3W: C 850 mg/m2 BID d1–14 + O 130 mg/m2 d1 + B 7.5 mg/kg d1 or Q2W: C 1500 mg/m2 BID d1–7 + O 85 mg/m2 d1 + B 5 mg/kg d1 for up to 72 weeks. Complete surgical resection was allowed using pre-defined criteria. The primary endpoint, progression-free survival (PFS), was estimated using the Kaplan- Meier method, while the hazard ratio and 95% CI were estimated using Cox regression analysis, based on the intent-to-treat population. No formal statistical testing was conducted. Results: The median PFS was 8.4 months (Q2W) and 9.7 months (Q3W) (hazard ratio [HR]=0.84; 95% CI=0.62–1.13). The median PFS (on-treatment) was 9.1 months and 10.2 months, respectively (HR=0.81). Of the 72 and 73 patients with disease progression (DP), the median time to DP was 9.4 and 10.8 months, respectively (HR=0.86). The objective response rates were 21.7% vs 29.4%, respectively (HR=1.05). Patients in the Q2W vs Q3W group experienced higher rates of grade 3/4 diarrhea (29% vs 24%), hand-foot syndrome (12% vs 8%), and treatment discontinuation rates (40% vs 20%), respectively. Other grade 3/4 toxicities (>5%, Q2W vs Q3W) included fatigue (13% vs 13%), dehydration (12% vs 10%), nausea (8% vs 9%), peripheral neuropathy (5% vs 9%), anorexia (5% vs 7%), and abdominal pain (5% vs 7%). Conclusions: At the dose and schedule used, dose-dense Q2W COB was not superior to standard Q3W COB. These data further confirm the activity and tolerability of Q3W COB. The activity and tolerability of a lower C dose Q2W, with more aggressive dose reduction, combined with B and O or irinotecan is currently being evaluated (X-BIO). [Table: see text]

390 The Impact of Extent of Resection on IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 293-294 ◽  
Author(s):  
Toral R Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany L Powell Avila ◽  
Gustav Y Cederquist ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Extent Of Resection ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Grade Ii ◽  
The Impact ◽  
Who Grade Ii Gliomas

Abstract INTRODUCTION Accumulating evidence suggests that maximizing extent of resection (EOR) improves outcomes for patients with WHO grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. To answer this question, we evaluated a cohort of patients with surgically-resection WHO grade II gliomas and known IDH1 mutation status, to assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS). METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing surgical resection at a single institution. EOR was assessed with quantitative three-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan-Meier method. RESULTS >52 (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median pre-operative tumor volume was 37.4 cm3 (range: 0.9-190.2 cm3). Median EOR was 57.6% (range: 0.08% 99.3%). Median follow-up was 44.4 months. Malignant progression was identified in 31 patients and 17 patients died. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, Cox regression analysis stratified by IDH status demonstrated that a greater EOR independently prolonged MPFS and OS for wtIDH patients (HR = 0.002 [95% CI 0.000 - 0.074] and HR = 0.001 [95% CI 0.00 - 0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17 - 4.13] and HR = 2.99 [95% CI 0.15 - 61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wild-type LGGs. However, the impact of EOR on IDH1 mutant LGGs is less significant and requires further study.

First-line PD1/PD-L1 inhibitors for platinum-ineligible advanced urothelial carcinoma (UC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 432-432 ◽  
Author(s):  
Archana Agarwal ◽  
Gregory Russell Pond ◽  
Alexandra Drakaki ◽  
Jae-Lyun Lee ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Complete Response ◽  
Phase Ii Trials ◽  
First Line ◽  
Cox Regression Analysis ◽  
Prospective Trials ◽  
The Mean ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3 ◽  
Ecog Ps

432 Background: FDA modified the label for the use of 1st-line pembrolizumab or atezolizumab therapy to PD-L1 high cisplatin-ineligible or platinum-ineligible UC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD1/PD-L1 inhibitors for platinum-ineligible pts are unclear. We conducted a retrospective study to evaluate clinical outcomes with first-line PD1/PD-L1 inhibitors for platinum-ineligible pts with advanced UC in a real-world setting. Methods: We collected data retrospectively from 6 institutions. The following criteria were deemed to render pts platinum-ineligible although physician discretion was also allowed: Cr Cl < 30 ml/min, ECOG-PS 3, Both Cr Cl 30 to < 60 AND ECOG-PS 2. Demographic and clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was done to study the association of baseline variables with response and survival. Results: Data were available for 45 pts. Pts received atezolizumab [n = 24], pembrolizumab [n = 11], nivolumab [n = 7] and durvalumab [n = 3]. The mean age was 72.2 (range 45-90) years. The reasons for platinum-ineligibility were: Cr Cl < 30 ml/min (n = 17), ECOG-PS 3 (n = 3), ECOG-PS 2 plus Cr Cl < 60 ml/min (n = 7), elderly with co-morbidities (n = 12), and reason was unavailable for 6 pts. The median OS was 37 weeks (CI 30-80). ORR was 27.3%: Complete response in 3 pts [6.8%], partial response in 9 pts [20.5%], stable disease in 11 pts [25%] and progressive disease in 21 pts [47.7%] and data for 1 patient was unavailable. Toxicity of any grade were seen in 42.2% of pts and Grade ≥3 toxicity in 9 pts’ [20%]. There were no treatment-related deaths. Anemia (HR = 0.75, 95% CI 0.62 - 0.92, P = 0.005) and liver metastasis (HR = 1.17, 95% CI 0.47 - 2.93, P = 0.017) correlated with shorter OS. Conclusions: To our knowledge, this is the 1st report of efficacy and toxicity of PD1/PD-L1 inhibitors as1st-line therapy for platinum ineligible UC. Data appear comparable to those reported previously in unselected cisplatin-ineligible pts receiving pembrolizumab or atezolizumab in phase II trials. Validation is needed in larger datasets and prospective trials.

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