Phase II trial of sunitinib malate and lomustine in patients with temozolomide refractory recurrent low-grade and anaplastic gliomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2050-2050
Author(s):  
Johnny Duerinck ◽  
Stephanie Du Four ◽  
An Van Binst ◽  
Hendrik Everaert ◽  
Alex Michotte ◽  
...  
Keyword(s):  
Metabolic Response ◽  
Clinical Investigation ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Anaplastic Glioma ◽  
Low Grade ◽  
Meaningful Activity ◽  
Anaplastic Gliomas ◽  
Daily Dose ◽  
Heavily Pretreated

2050 Background: Recurrent low-grade and anaplastic gliomas eventually transform to a higher grade that is characterized by neo-angiogenesis. Sunitinib inhibits multiple tyrosine kinase receptors (including VEGFR, PDGFR and c-Kit) but has no meaningful activity as a mono-therapy for recurrent glioblastoma when given at a daily dose of 37,5 mg (Neyns et al. J Neurooncol. 2011). We investigated sunitinib in combination with lomustine (CCNU) for the treatment of patients (pts) with temozolomide (TMZ) refractory recurrent low-grade or anaplastic glioma. Methods: Pts received a daily dose of 25 mg sunitinib for 28 consecutive days followed by a 14 days treatment-free interval. CCNU was administered as a single dose (80 mg/m²) on day 14 of a 6w cycle. T1 ± Gd and T2/FLAIR weighted MRI images were obtained q6 wks. 18FET-PET was performed at baseline and reassessed in responding pts. Results: 13 pts were enrolled (mean age 40 [range 33-49]; M/F 8/5; KPS 80-90/70-60: 8/5 pts). All pts had PD following surgery, RT and TMZ. In 7 pts, treatment was initiated at 2nd recurrence, in 4 pts at 3rd recurrence and in 2 pts at the 4th recurrence. Most frequent AEs where fatigue (gr 2: n= 3; gr 3: n= 1), thrombopenia (gr 2: n= 1 gr 3: n= 3 gr4: n= 1), neutropenia (gr 2: n= 2; gr3: n= 2; gr4: n= 2) and lymphopenia (gr 2: n=1; gr 3: n=2; gr 4: n=1). In 5/13 pts CCNU had to be discontinued because of AEs. Treatment with sunitinib was continued in these cases without reoccurrence of AEs. BOR according to RANO criteria: 1 CR, 1 PR (not-confirmed) and 2 SD (DCR: 4/13= 31%). In the patient with CR, FET-PET indicated a complete metabolic response. After a mean FU of 7 mths (range 2 -19), 5 pts are alive. The 6-month PFS is 23% (3/13 pts); median PFS is 1,8 mths (95%CI 1.0 - 2,7). A durable disease control was obtained in 3 pts (TTP respectively 14.8, 11.8+ and 19.2+ mths). Conclusions: in this heavily pretreated population with recurrent low-grade and anaplastic glioma the combination of sunitinib and CCNU is associated with acceptable toxicity and offers a durable progression-free survival in a subgroup of pts. Molecular predictive factors identifying the sensitive population would be needed to justify further clinical investigation of this combination.

scholarly journals Antiangiogenic Therapy for Patients with Recurrent and Newly Diagnosed Malignant Gliomas

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Katsuyuki Shirai ◽  
Michael R. Siedow ◽  
Arnab Chakravarti
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Antiangiogenic Therapy ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Targeting Therapy ◽  
Anaplastic Gliomas

Malignant gliomas have a poor prognosis despite advances in diagnosis and therapy. Although postoperative temozolomide and radiotherapy improve overall survival in glioblastoma patients, most patients experience a recurrence. The prognosis of recurrent malignant gliomas is dismal, and more effective therapeutic strategies are clearly needed. Antiangiogenesis is currently considered an attractive targeting therapy for malignant gliomas due to its important role in tumor growth. Clinical trials using bevacizumab have been performed for recurrent glioblastoma, and these studies have shown promising response rates along with progression-free survival. Based on the encouraging results, bevacizumab was approved by the FDA for the treatment of recurrent glioblastoma. In addition, bevacizumab has shown to be effective for recurrent anaplastic gliomas. Large phase III studies are currently ongoing to demonstrate the efficacy and safety of the addition of bevacizumab to temozolomide and radiotherapy for newly diagnosed glioblastoma. In contrast, several other antiangiogenic drugs have also been used in clinical trials. However, previous studies have not shown whether antiangiogenesis improves the overall survival of malignant gliomas. Specific severe side effects, difficult assessment of response, and lack of rational predictive markers are challenging problems. Further studies are warranted to establish the optimized antiangiogenesis therapy for malignant gliomas.

A phase II study of temozolomide and oral VP-16 for adults with recurrent glioma—Final results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1565-1565 ◽  
Author(s):  
D. N. Korones ◽  
M. Benita-Weiss ◽  
T. Coyle ◽  
P. Bushunow ◽  
L. Mechtler ◽  
...  
Keyword(s):  
Phase 1 ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Low Grade Glioma ◽  
Recurrent Glioma ◽  
Low Grade ◽  
Entire Cohort ◽  
Low Grade Gliomas ◽  
Prior Therapy ◽  
Anaplastic Gliomas

1565 Background: Although temozolomide has proven activity in patients with high and low grade gliomas, many patients do not respond, and for those who do, responses are often short-lived. We therefore undertook a trial of temozolomide in combination with oral VP-16 (etoposide) for patients with recurrent glioma. Methods: Patients were eligible for the study if they had recurrence of a glioma (glioblastoma [GBM], anaplastic glioma, or low-grade glioma), were ≥ 18 years of age, had a WHO score of 0–2, and had not received prior therapy with temozolomide or oral VP-16. All patients received temozolomide, 150 mg/m2/d days 1–5 and oral VP-16, 50 mg/m2/d days 1–12 (based on the maximum tolerated dose established in a previous phase 1 study [Cancer 2003, 97 (8); 1963–68.]). Cycles were repeated every 28 days for up to 12 cycles. All patients received prophylaxis for pneumocystis. Results: Fifty-one patients were enrolled - 32 with glioblastoma, 12 with anaplastic gliomas, and 7 with low-grade glioma. Median age was 52 years (21–76), and 67% were male. Forty-one were enrolled at first and 10 at second recurrence. Fifty had had prior radiation, and 30 of these 50 patients had also received prior chemotherapy. Of the 32 subjects with GBM, 4 had a PR (12.5%), 13 (41%) SD, 13 (41%) PD, and 2 were not evaluable because of deterioration prior to imaging. The median progression-free survival (PFS) was 2 mo. (0–51+ mo), and the 6 mo. PFS was 19%. Of the 12 patients with anaplastic gliomas, 2 had a PR (16%), 7 SD (58%), 2 PD (16%) and one was not evaluable. Their median PFS was 5.5 mo, and the 6 mo. PFS was 50%. Of the seven subjects with low grade gliomas, 4 had a PR, 2 SD, and 1 PD. Their median PFS was 5 mo. (0–12) and 6 mo. PFS was 57%. Of the entire cohort, two patients developed fever and neutropenia and died of pseudomonas sepsis. Another two patients were prematurely withdrawn from the study due to toxicity (one for grade 4 neutropenia and a second for grade 2 diarrhea). Conclusions: In this population of previously treated patients with recurrent glioma, the combination of oral VP-16 and temozolomide has only modest efficacy and significant toxicity. The results of this study suggest that in this setting, the combination offers no advantage over either agent used alone. [Table: see text]

Phase II trial of BPM31510-IV plus gemcitabine in advanced pancreatic ductal adenocarcinomas (PDAC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 723-723
Author(s):  
Madappa N. Kundranda ◽  
David Propper ◽  
Paul S. Ritch ◽  
James Strauss ◽  
Manuel Hidalgo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Response ◽  
Clinical Investigation ◽  
Progression Free Survival ◽  
Best Response ◽  
Investigation Methods ◽  
Patient Reported ◽  
Heavily Pretreated ◽  
To Receive

723 Background: BPM31510-IV is an Ubidecarenone (CoQ10) drug-lipid conjugate nanodispersion targeting metabolic machinery in cancer, shifting bioenergetics from lactate dependency towards mitochondrial OxPhos to generate ROS and activate apoptosis. An MTD of BPM31510-IV in combination with gemcitabine was established at 110mg/kg in a Phase I clinical trial, which determined the dose for the Phase 2 investigation. Methods: Eligible patients (aged ≥ 18 y) with relapsed/refractory PDAC to standard treatment (ST) and met inclusion/exclusion criteria were recruited. Patients received 110mg/kg IV BPM31510 in combination with gemcitabine in a 144-hour infusion. Tumor response was evaluated at week 10 and then every 8 weeks. Study endpoints assessed were Overall Response Rate (ORR), Overall Survival (OS), Progression-Free Survival (PFS), Time to Progression (TTP), Tumor Response using Adaptive Molecular Responses (multi-omic molecular profiling), changes in CA 19-9 levels and patient reported Quality of Life (QOL) using the validated FACT-HEP PRO. A comprehensive multi-omic profiling for identification of biomarkers for patient stratification was explored. Results: Of the 35 patients enrolled to receive therapy, 18 patients met criteria of an adequately treated cohort (ATC- received BPM31510-IV + gemcitabine for 30 days over 2 cycles and had a RECIST 1.1 evaluation) while remaining (n = 17) had progressive disease (PD). Half of the ATC population (n = 9/18, 50%) achieved best ORR of stable disease (SD); 10/18 (55 %) demonstrated SD as best response at target lesions and 8/18 demonstrated SD at end of Cycle 2. The mTTP was 121 days (70 – 147, 95% CI); PFS 118 days (70 – 131, 95% CI) and OS 218 days (131 – 228, 95% CI), respectively. Overall, BPM31510-IV was well tolerated; the most common AE’s were GI related. Conclusions: The efficacy signal observed in this heavily pretreated population in addition to the toxicity profile warrants further clinical investigation of BPM31510-IV + gemcitabine in advanced PDAC. Clinical trial information: NCT02650804 . [Table: see text]

scholarly journals Phase II Trial of Single-Agent Bevacizumab Followed by Bevacizumab Plus Irinotecan at Tumor Progression in Recurrent Glioblastoma

2009 ◽  
Vol 27 (5) ◽  
pp. 740-745 ◽  
Author(s):  
Teri N. Kreisl ◽  
Lyndon Kim ◽  
Kraig Moore ◽  
Paul Duic ◽  
Cheryl Royce ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Progression ◽  
Bowel Perforation ◽  
Single Agent ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Thromboembolic Events ◽  
Macdonald Criteria ◽  
Heavily Pretreated ◽  
Antiglioma Activity

Purpose To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma. Patients and Methods Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m2 or 125 mg/m2 every 2 weeks, depending on use of enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated every 4 weeks. Results Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses. Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days. Conclusion We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.

scholarly journals Response assessment of novoTTF-100A versus best physician’s choice chemotherapy in recurrent glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2080-2080
Author(s):  
Eric Wong ◽  
Edwin Lok ◽  
Kenneth D. Swanson ◽  
Shiva Gautam ◽  
Herbert H. Engelhard ◽  
...  
Keyword(s):  
Electric Fields ◽  
Pearson Correlation ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response Assessment ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Low Grade ◽  
Median Response ◽  
Macdonald Criteria

2080 Background: The NovoTTF-100A device emits tumor treating electric fields and was tested against Best Physician’s Choice (BPC) chemotherapy in a randomized phase III trial. We analyzed post hoc the characteristics of responders and non-responders in both cohorts. Methods: Macdonald criteria were used to determine tumor response and progression. Kaplan-Meier and Chi-squared statistics were computed for time to response, response duration, progression-free survival (PFS) with and without Simon-Makuch correction, and overall survival (OS). Prognostic factors were compared using the Wilconox rank sum test. Relative hazard rates for responders and non-responders were plotted. Results: The median response duration was 7.3 versus 5.6 months for NovoTTF-100A and BPC chemotherapy respectively (p=0.0009). Five of 14 NovoTTF-100A responders but none of 7 BPC responders had prior low-grade histology. The mean cumulative dexamethasone dose was 35.9 mg for responders versus 485.6 mg for non-responders in the NovoTTF-100A cohort (p<0.0001) as compared to 525.6 mg for responders and 431.0 mg for non-responders in the BPC cohort (p=0.9520). Hazard rate analysis showed delayed tumor progression in responders compared to non-responders. The Simon-Makuch conditional plot, which adjusted for unequal progression-free states, still showed longer PFS in responders than non-responders treated with NovoTTF-100A (χ2=11.5, P=0.0007) or BPC chemotherapy (χ2=5.2, P=0.0222). The median OS was 24.8 months for responders that is longer than 6.2 months for non-responders treated with NovoTTF-100A (χ2=25.7, P<0.0001). In the BPC chemotherapy cohort, the median OS was 20.0 months for responders and 6.8 months for non-responders (χ2=5.1, P=0.0235). There was strong Pearson correlation between response and OS in NovoTTF-100A (P<0.0002) but not in BPC cohort (P=0.2952). Conclusions: Response duration, adjusted Simon-Makuch PFS and OS favor NovoTTF-100A over BPC chemotherapy. Data on prior low-grade histology and dexamethasone dose suggest potential genetic and epigenetic determinants of NovoTTF-100A response. Clinical trial information: NCT00379470.

Impact of duration of bevacizumab (Bev) treatment in the prognosis of adults with recurrent malignant gliomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2064-2064
Author(s):  
Mohamed Ali Hamza ◽  
Charles A. Conrad ◽  
John Frederick De Groot ◽  
Mark R. Gilbert ◽  
Morris D. Groves ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Duration Of Treatment ◽  
Length Of Treatment ◽  
Anaplastic Gliomas ◽  
Bevacizumab Treatment ◽  
Significant Difference ◽  
Prospective Trials ◽  
The Relationship

2064 Background: Bev is the standard treatment for patients with recurrent glioblastoma (GB) but is also used in treating recurrent anaplastic gliomas (AG). Differences in outcome between these groups and optimal duration of treatment with Bev in pts with recurrent malignant gliomas are not well defined. We examined the relationship between the duration of Bev treatment and the outcome in pts with GB and AG. Methods: In this retrospective chart and data review derived from our longitudinal database, we identified pts with recurrent AG and GB who were treated with Bev alone or Bev-containing regimens between 2005 and 2009; the data was analyzed to determine the overall survival (OS) and the progression free survival (PFS). Results: A total of 261 patients with recurrent malignant gliomas (196 with GB and 65 with AG) were identified. There was no significant difference between the median length of treatment between AG and GB (5.81±0.66 months vs. 6.77±0.52 months, p=0.32). PFS6 was 34.2% (95% CI, 27.8-41.3) for patients with GB and 44.2% (95% CI, 32.5-56.7) for patients with AG. Patients with GB who were treated ≥6 months had a significantly higher OS (29.13 months vs. 20.16 months, p= 0.001) compared to those treated <6 months, and a significantly higher PFS compared to those treated <6months (11.33 months vs. 3.7 months, p=0.0001). For patients with AG, although treatment ≥6 months had a significantly higher PFS (13.93 months vs. 3.53 months, p<0.0001), OS was not significantly different (months 38.6 vs. 52.5 months, p=0.6) compared with those treated <6 months. Conclusions: Length of treatment ≥6 mo with Bev or Bev-containing regimen was associated with improved PFS in both AG and GB but only the GB subgroup showed improved OS. These results suggest equivocal survival benefit in patients with AG with longer duration of bevacizumab treatment, which requires further study in prospective trials.

scholarly journals OS6.5 ERGO2: A prospective randomized trial of a 9-day schedule of calorically restricted ketogenic diet and fasting or standard diet in addition to re-irradiation for malignant glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii13-iii13
Author(s):  
M Voss ◽  
M Wagner ◽  
N von Mettenheim ◽  
P N Harter ◽  
K Wenger ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Epileptic Seizures ◽  
Recurrent Glioblastoma ◽  
Intermittent Fasting ◽  
Standard Diet ◽  
Glucose Levels ◽  
Heavily Pretreated ◽  
Set Up

Abstract BACKGROUND Ketogenic diet (KD) and fasting have anticancer effects in tumor models, possibly due to a differential stress response with sensitization of tumor cells and protection of normal tissue. We therefore set up ERGO2 (NCT01754350), the first randomized clinical trial of calorically-restricted KD and intermittent fasting (KD-IF) in addition to re-irradiation for recurrent malignant gliomas. MATERIAL AND METHODS Patients were randomized 1:1 to re-irradiation combined with either calorically unrestricted diet (standard diet, SD) or KD-IF. The KD-IF schedule included 3 days of KD (21–23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. The primary endpoint was progression-free survival (PFS) rate at 6 months (PFS6). Secondary endpoints were PFS, local control, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. RESULTS 50 patients were included. Four patients quit the trial before treatment and three patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6, and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1±1.8 kg. No severe adverse events attributable to the diet occurred. There was no difference in PFS6 between the two groups (KD-IF: 20%, SD: 16%). Similarly, no difference in PFS, local PFS6 and OS were observable. Explorative analysis revealed that among patients of the KD-IF group, those who achieved ketosis of at least 1.5 mmol/l had significantly longer PFS compared to those with lesser or no ketosis. CONCLUSION KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioblastoma. However, the short schedule reported here failed to increase the efficacy of re-irradiation.

scholarly journals Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study

2011 ◽  
Vol 29 (19) ◽  
pp. 2689-2695 ◽  
Author(s):  
John F. de Groot ◽  
Kathleen R. Lamborn ◽  
Susan M. Chang ◽  
Mark R. Gilbert ◽  
Timothy F. Cloughesy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Malignant Glioma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Anaplastic Glioma ◽  
Recurrent Malignant Glioma ◽  
Free Survival

Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma.

Anaplastic gliomas: Is there a role for aggressive concomitant treatment?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13050-e13050
Author(s):  
Luiz Gustavo Sueth Berriel ◽  
Fábio Nasser Santos ◽  
Ana Carolina Sigolo Levy Diniz ◽  
Ludmilla Thome Chinen ◽  
Alexandre Andre Balieiro Anastacio da Costa
Keyword(s):  
Adjuvant Treatment ◽  
Therapy Group ◽  
Progression Free Survival ◽  
Anaplastic Glioma ◽  
Concomitant Treatment ◽  
Rare Type ◽  
Concomitant Radiochemotherapy ◽  
Anaplastic Gliomas ◽  
Grade 3 ◽  
Sequential Radiochemotherapy

e13050 Background: Anaplastic glioma is a rare type of glioma, therefore there is no standard treatment after surgery. Adjuvant treatment possibilities are monotherapy with radiotherapy or chemotherapy, or combination therapy done concomitantly or sequentialy. Methods: A comparison of adjuvant treatments in a retrospective analysis of 64 patients with the diagnosis of anaplastic glioma treated at A.C.Camargo Hospital, Sao Paulo-Brazil, from 1994 to 2012. Results: Fifty-eight percent were male, median age 42yo (16-79yo), 76,6% ECOG 0-1, Histopatology was 76,6% astrocytomas, 9,4% oligoastrocytomas and 14% oligodendrogliomas. Adjuvant treatment was concomitant radiochemotherapy in 45, 2%, sequential radiochemotherapy in 14,5%, radiotherapy-only in 16,1%, chemotherary-only in 9,7% and 14,5% received no adjuvant treatment. With a median follow up of 32,2mo (P25-P75 – 13, 3-62, 9mo), median progression free survival (mPFS) was 65mo (CI 29,2 – 100,7mo) and median overall survival (mOS) was 87mo (CI 26,3 – 147,7mo) in the whole group. There was a mOS of 31,4mo for astrocytomas, 89,2mo for oligoastrocytomas and not reached for oligodendrogliomas. Comparing with other treatments, the concomitant therapy group had a longer mPFS (124,8mo vs. 20mo, p: 0,016) and mOS (139,8mo vs. 27,9mo, p = 0.081). When only anaplastic astrocytoma where analyzed, treatment with concomitant radiochemotherapy had better mPFS (p = 0.01) and mOS (p = 0.033). On the other side, treatment with sequential radiochemotherapy didn’t have such impact in either mPFS (p: 0,22) or mOS (p: 0,27). Prognostic factors related with both mPFS and mOS in the whole group were astrocytic histology, multiple lesions and more than 50yo at diagnosis. Non-cortical lesions were also prognostic for mOS. In the multivariate analysis, treatment with concomitant radiochemotherapy had an impact at mPFS (HR 0,28, p = 0.006) and mOS (HR 0,44, p = 0.039). Conclusions: Since there is no standard adjuvant treatment for anaplastic gliomas, evidence for treatment is often taken from GBM studies. This study suggests that an aggressive strategy, like concomitant radiochemotherapy with temozolamide, is useful in grade 3 gliomas, specially in astrocystic histology.

Glofitamab step-up dosing (SUD): Complete response rates in updated efficacy data in heavily pretreated relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) patients (pts).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7519-7519
Author(s):  
Carmelo Carlo-Stella ◽  
Martin Hutchings ◽  
Fritz C. Offner ◽  
Franck Morschhauser ◽  
Emmanuel Bachy ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Metabolic Response ◽  
Response Rates ◽  
Complete Response ◽  
Low Grade ◽  
Target Dose ◽  
Efficacy Data ◽  
Efficacy Analysis ◽  
Non Hodgkin Lymphoma ◽  
Heavily Pretreated

7519 Background: Glofitamab (RG6026), a T-cell-engaging, bispecific, full-length antibody, allows bivalent binding to CD20 (B-cells), and monovalent binding to CD3 (T-cells). In NP30179 (NCT03075696), an ongoing multicenter, Phase I dose-escalation and expansion study, 0.6–25mg glofitamab fixed-dosing with obinutuzumab pretreatment (Gpt), showed high, durable complete responses and manageable safety in heavily pretreated R/R NHL (Dickinson, et al. EHA 2020). Glofitamab SUD, in addition to Gpt, allowed dose escalation up to 30mg to maximize efficacy, while mitigating cytokine release syndrome (CRS) (Hutchings, et al. JCO 2021). We present updated efficacy data from glofitamab monotherapy SUD cohorts. Methods: Gpt (1000mg) was given to pts 7 days pre-glofitamab initial dose. Intravenous SUD of glofitamab was given on Day (D) 1 and 8 of Cycle (C) 1 and then at the target dose from C2D1 (2.5/10/16mg or 2.5/10/30mg); treatment continued for up to 12 cycles, every 21 days. Response rates were based on the Lugano criteria (Cheson, et al. JCO 2014). Results: Fifty-two pts received glofitamab SUD; 17 and 35 pts received 2.5/10/16mg and 2.5/10/30mg, respectively. Twenty-eight pts (53.8%) had aggressive NHL (aNHL) and 24 pts had indolent NHL (iNHL). Pts had a median age of 68 (44–85) years and received a median of 3 (1–12) prior lines of therapy. Forty (76.9%) and 38 (73.1%) pts were refractory to their most recent and any prior CD20 therapy, respectively. After a median follow-up of 6.3 months, an updated efficacy analysis was conducted on December 1, 2020. For pts with aNHL (N = 28), the best overall response (OR) and complete metabolic response (CMR) rates were 64.3% and 57.1%, respectively; a trend of improved response was observed with increased target dose, with a CMR rate of 71.4% at 2.5/10/30mg (N = 14). Notably, 4/5 pts (80%) with mantle cell lymphoma (2.5/10/16mg, n = 2; 2.5/10/30mg, n = 2) had CMR. For aNHL, 13/16 CMRs are ongoing, with 8 CMRs lasting > 3 months. For pts with iNHL (N = 24), OR and CMR rates were 79.2% and 70.8%, respectively; 14/17 CMRs are ongoing, with 10 CMRs lasting > 3 months. As of August 3, 2020, common adverse events (52 pts) were CRS (63.5%), neutropenia (38.5%), and pyrexia (32.7%). CRS was mostly confined to C1: 24/50 pts had CRS after 2.5mg; 20/49 pts after 10mg; 2/16 and 8/32 pts had CRS after 16 and 30mg (C2D1), respectively. Grade [Gr] 1 and 2 CRS was reported in 18 (34.6%) and 12 (23%) pts, respectively; 3 pts had Gr 3 CRS; none had Gr 4/5 events (ASTCT 2019). Updated data, including biomarker data on baseline CD20 expression and CD8 levels in the tumor, will be presented. Conclusions: Updated data for glofitamab monotherapy SUD show higher preliminary response rates than previously reported in pts with R/R NHL who have failed multiple lines of therapy. CRS was mostly manageable, of low grade, and confined to the first cycle of treatment. Clinical trial information: NCT03075696.

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