EF-19, a post-approval registry study of tumor treating fields (TTFields) in recurrent glioblastoma (rGBM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14536-e14536
Author(s):  
Jay-Jiguang Zhu ◽  
Robert O'Donnell ◽  
Zvi Ram
Keyword(s):  
Adverse Events ◽  
Treatment Failure ◽  
Real Life ◽  
Recurrent Glioblastoma ◽  
Rank Test ◽  
Registry Study ◽  
Eligibility Criteria ◽  
Time To Treatment ◽  
Tumor Treating Fields ◽  
Time To Treatment Failure

e14536 Background: Tumor Treating Fields (TTFields) are an anti-mitotic non-invasive therapy of low intensity alternating electric fields delivered to the tumor via a portable medical device. In phase 3 studies that led to FDA approvals, TTFields plus maintenance temozolomide significantly extended survival in newly diagnosed GBM, and achieved comparable survival outcome to best standard of care (BSC) as monotherapy in recurrent GBM (rGBM). The EF-19 study aimed to confirm efficacy of TTFields vs BSC in rGBM in post-approval real-life setting. Methods: This non-inferiority, prospective, non-randomized, post approval registry trial enrolled 192 rGBM patients (>21 yrs, KPS > 70). Patients were treated with TTFields (200 kHz, > 18h/day). Eligibility criteria: histologic GBM, past treatment per Stupp protocol for primary disease and radiological evidence of progression in the supratentorial region. Primary endpoint was overall survival (OS); secondary endpoints were OS in the per protocol (PP) population ( > 1 course of TTFields or BSC in each respective arm), time to treatment failure and adverse events. The TTFields patient registry data were compared to OS of all 117 rGBM patients in the BSC group of the EF-11 trial (Stupp R, EJC 2012). The sample size of 192 patients (10% loss to follow up) was based on non-inferiority log-rank test with a two-sided alpha level of 0.05 and a power of 80%, comparing time to event (i.e., death) between patients treated with TTFields and BSC. The analysis was based on true hazard ratio (HR) of 1.0 comparing TTFields to control with an upper one-sided 95% confidence bound of HR not exceeding 1.375. Results: Median OS with TTFields versus EF-11 BSC was 7.4 vs. 6.4 months, p = 0.053; HR = 0.64 (95%CI 0.46-0.91, Cox-test P = 0.012). Median OS (PP population) with TTFields versus EF-11 BSC was 8.1 months vs. 6.5 months; p = 0.045; HR 0.65. The results showed a significant superiority in HR of OS between the 2 groups, as the 95% confident interval upper limit of the HR was lower than the pre-defined threshold for non-inferiority for interval bound of 1.375. The overall incidence of adverse event was lower with TTFields than EF-11 BSC (67% vs. 95%). The median time to treatment failure was longer in the TTFields arm (3.3 months (95% CI 2.6, 3.9) versus BSC arm (1.6 months; 95% CI 1.1, 1.9); HR = 0.53 (95% CI 0.41, 0.68, p < 0.0001). Skin AE was the most frequently reported AEs in TTFields arm; no unexpected adverse events were reported with TTFields. Conclusions: The results of the EF-19 registry study confirm the effectiveness and safety of TTFields monotherapy in rGBM.

scholarly journals CTNI-77. EF-19, A POST-APPROVAL REGISTRY STUDY OF TUMOR TREATING FIELDS (TTFIELDS) IN RECURRENT GLIOBLASTOMA (rGBM)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii60-ii60
Author(s):  
Jay-Jiguang Zhu ◽  
Robert T O’Donnell ◽  
Samuel Goldlust ◽  
Zvi Ram
Keyword(s):  
Treatment Failure ◽  
Electric Fields ◽  
Real Life ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
Rank Test ◽  
Registry Study ◽  
Time To Treatment ◽  
Tumor Treating Fields ◽  
Time To Treatment Failure

Abstract BACKGROUND Tumor Treating Fields (TTFields) are an anti-mitotic therapy of alternating electric fields delivered non-invasively to the tumor. In phase 3 studies leading to FDA-approvals, TTFields plus temozolomide (TMZ) significantly extended survival in newly diagnosed GBM, and achieved comparable survival to best standard of care (BSC) as monotherapy in recurrent GBM (rGBM). The EF-19 study evaluated efficacy of TTFields vs BSC in rGBM in post-approval real-life setting. METHODS This registry trial (192 rGBM patients, &gt;21 yrs, KPS &gt; 70) were treated with TTFields (200 kHz, &gt;18h/day). Primary endpoint was overall survival (OS); secondary endpoints were OS in the per protocol (PP) population, time to treatment failure and adverse events (AEs). The registry data were compared to OS of all 117 patients in EF-11 BSC group (Stupp EJC 2012). The sample size (N=192) was based on non-inferiority log-rank test with two-sided alpha (0.05), 80% power, HR of 1.0 comparing TTFields to control with an upper one-sided 95% CI of HR &lt; 1.375. RESULTS Median OS with TTFields versus EF-11 BSC was 7.4 versus 6.4 months, p=0.053; HR = 0.64 (95%CI 0.46–0.91, Cox-test P=0.012). Median OS (PP) with TTFields versus EF-11 BSC was 8.1 months versus 6.5 months; p=0.045; HR 0.65. OS was significantly higher TTFields as the 95% CI upper limit of HR was lower than the pre-defined threshold of 1.375. The overall incidence of AEs was lower with TTFields than EF-11 BSC (67% vs. 95%). The median time to treatment failure was longer in the TTFields arm (3.3 months (95% CI 2.6, 3.9) versus BSC arm (1.6 months; 95% CI 1.1, 1.9); HR=0.53 (95% CI 0.41, 0.68, p&lt; 0.0001). Skin AE was the most common AE in the TTFields arm. CONCLUSION The results of the EF-19 registry study confirm the effectiveness and safety of TTFields monotherapy in rGBM.

scholarly journals Microsurgical rhizotomy for trigeminal neuralgia in MS patients: technique, patient satisfaction, and clinical outcomes

2019 ◽  
Vol 130 (6) ◽  
pp. 1877-1888
Author(s):  
Mark G. Bigder ◽  
Sandeep Krishnan ◽  
E. Francis Cook ◽  
Anthony M. Kaufmann
Keyword(s):  
Trigeminal Neuralgia ◽  
Treatment Failure ◽  
Rank Test ◽  
Control Group ◽  
Chi Square ◽  
Time To Treatment ◽  
Pain Scores ◽  
Kaplan Meier ◽  
Time To Treatment Failure ◽  
Chi Square Test

OBJECTIVEPatients with multiple sclerosis (MS)–associated trigeminal neuralgia (TN) have higher recurrence and retreatment rates than non-MS patients. The optimal management strategy and role for microsurgical rhizotomy (MSR) for MS-TN remains to be determined. The aim of this study was to report time to treatment failure (TTF) and pain scores following MSR compared to percutaneous and Gamma Knife procedures.METHODSTime to treatment failure was analyzed after MSR (n = 14) versus prior procedures (n = 53) among MS-TN patients. Kaplan-Meier curves and log-rank test were utilized to compare TTF after MSR versus prior procedures using the same cohort of patients as their own control group. Subsequent analysis compared TTF after MSR to TTF after 93 other procedures among a second cohort of 18 MS-TN patients not undergoing MSR. BNI pain scores were compared between MSR and other procedures among the MS-TN cohort using a chi-square test.RESULTSTTF was significantly longer after MSR than after other procedures in the MSR cohort (median TTF 79 vs 10 months, respectively, p < 0.0001). Similarly, TTF was longer after MSR than after prior procedures in the non-MSR cohort (median TTF 79 vs 13 months, respectively, p < 0.001). MSR resulted in a higher proportion of excellent pain scores when compared to other procedures in the non-MSR cohort (77% vs 29%, p < 0.001). Probability of treatment survival was higher after MSR than after other procedures at all time points (3, 6, 12, 24, 36, and 48 months). There were no deaths or major complications after MSR.CONCLUSIONSTTF was significantly longer following MSR compared to prior procedures in MS-TN patients. Additionally, a higher proportion of patients achieved excellent BNI pain scores after MSR.

scholarly journals Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center

2015 ◽  
Vol 33 (28) ◽  
pp. 3193-3198 ◽  
Author(s):  
Troy Z. Horvat ◽  
Nelly G. Adel ◽  
Thu-Oanh Dang ◽  
Parisa Momtaz ◽  
Michael A. Postow ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Treatment Failure ◽  
Systemic Corticosteroid ◽  
Standard Dose ◽  
Corticosteroid Treatment ◽  
Cancer Center ◽  
Time To Treatment ◽  
Systemic Corticosteroids ◽  
Time To Treatment Failure

Purpose Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF). Patients and Methods We reviewed retrospectively the medical records of patients with melanoma who had received treatment between April 2011 and July 2013 with ipilimumab at the standard dose of 3 mg/kg. We collected data on patient demographics, previous and subsequent treatments, number of ipilimumab doses, irAEs and how they were treated, and overall survival. Results Of the 298 patients, 254 (85%) experienced an irAE of any grade. Fifty-six patients (19%) discontinued therapy because of an irAE, most commonly diarrhea. Overall, 103 patients (35%) required systemic corticosteroid treatment for an irAE; 29 (10%) also required anti-TNFα therapy. Defining TTF as either starting a new treatment or death, estimated median TTF was 5.7 months. Twelve percent of patients experienced long-term disease control without receiving additional antimelanoma therapy. OS and TTF were not affected by the occurrence of irAEs or the need for systemic corticosteroids. Conclusion IrAEs are common in patients treated with ipilimumab. In our experience, approximately one-third of ipilimumab-treated patients required systemic corticosteroids, and almost one-third of those required further immune suppression with anti-TNFα therapy. Practitioners and patients should be prepared to treat irAEs and should understand that such treatment does not affect OS or TTF.

Biomarkers of prolonged time to treatment failure in metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: A real life patients-based nomogram and web app.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 202-202
Author(s):  
Maysa Tamara Silveira Vilbert ◽  
Natasha Carvalho Pandolfi ◽  
Marcelle Goldner Cesca ◽  
Vinicius Fernando Calsavara ◽  
Marcelo Corassa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Failure ◽  
Statistical Tests ◽  
Real Life ◽  
Predictive Biomarkers ◽  
Castration Resistant Prostate Cancer ◽  
Time To Treatment ◽  
Castration Resistant ◽  
Time To Treatment Failure ◽  
Web App

202 Background: Survival outcomes for metastatic castration resistant prostate cancer (mCRPC) patients (pts) have greatly improved following the approval of Docetaxel and abiraterone(Abi)/enzalutamide(Ez). However, it is not clear who is likely to benefit more from these therapies in real life clinical practice. Methods: A retrospective cohort study was performed with mCRPC pts treated with Abi/Ez in pre-Docetaxel setting. Primary endpoint: to identify predictive biomarkers of long time to treatment failure (TTF), develop a nomogram and convert it into a web app. Secondary endpoint: to correlate biomarkers with overall survival (OS). Kaplan Meier survival estimates and Cox Regression models were used for time-to-event analyses. Statistical analysis was made with R software. All statistical tests were two-sided and statistical significance was fixed at 0.05. Results: From May2012 to October2017, 117 pts were assessed, 81 received Abi and 36 Ez. Median follow-up of 21 months (mo), estimated median TTF was 12.8mo (95%CI 9.98-15.7) for the total population. Predictive biomarkers for TTF included in the first nomogram model were time from start of androgen deprivation therapy (tADT) to start of Abi/Ez, pain at baseline, Gleason score, baseline testosterone and lower PSA nadir in castration sensitive prostate cancer (CSPC). The second nomogram model included pain and Gleason plus neutrophil counts, tADT to CRPC and baseline PSA at CRPC. C-index: 0.726 and 0.731 respectively, providing a reliable prediction of long-term benefit with Abi/Ez in this setting. All these characteristics were significantly associated with OS. Conclusions: The two nomogram achieved a good internal validation and can work as a tool to the decision-making process of the best strategy to first-line therapy in mCRPC pts.[Table: see text]

Time to treatment failure of palbociclib and letrozole as second-line therapy or beyond in hormone receptor-positive advanced breast cancer

2018 ◽  
Vol 25 (6) ◽  
pp. 1374-1380 ◽  
Author(s):  
M Alexandra Schickli ◽  
Michael J Berger ◽  
Maryam Lustberg ◽  
Marilly Palettas ◽  
Craig A Vargo
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Failure ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Second Line ◽  
Time To Treatment ◽  
Cyclin Dependent Kinases ◽  
Hormone Receptor Positive ◽  
Time To Treatment Failure

Purpose The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy. Methods This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond. Results Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1–7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9–8.3 months). Conclusions Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.

Randomized Phase II Comparison of Dose-Intense Gemcitabine: Thirty-Minute Infusion and Fixed Dose Rate Infusion in Patients With Pancreatic Adenocarcinoma

2003 ◽  
Vol 21 (18) ◽  
pp. 3402-3408 ◽  
Author(s):  
Margaret Tempero ◽  
William Plunkett ◽  
Veronique Ruiz van Haperen ◽  
John Hainsworth ◽  
Howard Hochster ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Dose Rate ◽  
Pancreatic Adenocarcinoma ◽  
Median Survival ◽  
Phase Ii ◽  
Fixed Dose ◽  
Time To Treatment ◽  
Randomized Phase Ii ◽  
Fixed Dose Rate ◽  
Time To Treatment Failure

Purpose: To conduct a randomized phase II trial of dose-intense gemcitabine using a standard 30-minute infusion or the fixed dose rate (FDR) infusion (10 mg/m2/min) in patients with pancreatic adenocarcinoma. Patients and Methods: In this prospective trial, patients with locally advanced and metastatic pancreatic adenocarcinoma were treated with 2,200 mg/m2 gemcitabine over 30 minutes (standard arm) or 1,500 mg/m2 gemcitabine over 150 minutes (FDR arm) on days 1, 8, and 15 of every 4-week cycle. The primary end point of this trial was time to treatment failure. Secondary end points included time to progression, median survival, safety, and pharmacokinetic studies of gemcitabine. Results: Ninety-two patients were enrolled onto this study; 91% of the patients had metastatic disease. Time to treatment failure was comparable in both treatment groups; however, the median survival for all patients was 5.0 months in the standard arm and 8.0 months in the FDR arm (P = .013). For patients with metastases, the median survival was 4.9 months in the standard arm and 7.3 months in FDR arm (P = .094). The 1- and 2-year survival rates for all patients were 9% (standard arm) versus 28.8% (FDR; P = .014) and 2.2% (standard arm) versus 18.3% (FDR; P = .007), respectively. Patients in the FDR infusion arm experienced consistently more hematologic toxicity. Pharmacokinetic analyses demonstrated a two-fold increase in intracellular gemcitabine triphosphate concentration in the FDR arm (P = .046). Conclusion: Pharmacokinetic and clinical data in this trial supports the continued evaluation of the FDR infusion strategy with gemcitabine.

Phase II Study of Phenylacetate in Patients With Recurrent Malignant Glioma: A North American Brain Tumor Consortium Report

1999 ◽  
Vol 17 (3) ◽  
pp. 984-984 ◽  
Author(s):  
Susan M. Chang ◽  
John G. Kuhn ◽  
H. Ian Robins ◽  
S. Clifford Schold ◽  
Alexander M. Spence ◽  
...  
Keyword(s):  
Body Weight ◽  
Treatment Failure ◽  
Malignant Glioma ◽  
Plasma Concentrations ◽  
Ideal Body Weight ◽  
Dose Schedule ◽  
Recurrent Malignant Glioma ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
Ideal Body

PURPOSE: To determine the response rate, time to treatment failure, and toxicity of phenylacetate in patients with recurrent malignant glioma and to identify plasma concentrations achieved during repeated continuous infusion of this agent. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma were treated with phenylacetate. The schedule consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off). A starting dose of 400 mg/kg total body weight per day of phenylacetate was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer Institute common toxicity criteria were used to assess toxicity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed. RESULTS: Forty-three patients were enrolled between December 1994 and December 1996. Of these, 40 patients were assessable for toxicity and response to therapy. Reversible symptoms of fatigue and somnolence were the primary toxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2 months, seven (17.5%) had stable disease, and three (7.5%) had a response defined as more than 50% reduction in the tumor. Median time to treatment failure was 2 months. Thirty-five patients have died, with a median survival of 8 months. Pharmacokinetic data for this dose schedule showed no difference in the mean plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5 and 6. CONCLUSION: Phenylacetate has little activity at this dose schedule in patients with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule.

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