Temozolomide In Patients Research Articles

Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review.

Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility criteria included patients 16 years of age and older, notation of LGG subtype, and report of progression-free survival (PFS), overall survival (OS), and treatment course. Level I, II, and III data were included. Adjuvant therapy with PCV resulted in prolonged PFS and OS in patients with newly diagnosed high-risk LGG. This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation. Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV. In patients with LGG with an unfavorable natural history, such as with intact 1p/19q and wild-type IDH1, RT/TMZ plus adjuvant TMZ may be the best option. Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV.

Bevacizumab therapy for recurrent gliomas: another disappointment?

In their Article in The Lancet Oncology, Martin van den Bent and colleagues 1 van den Bent MJ Klein M Smits M et al. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol. 2018; (published online Aug 13)http://dx.doi.org/10.1016/S1470-2045(18)30362-0 Summary Full Text Full Text PDF Scopus (60) Google Scholar report on their clinical trial of bevacizumab in the treatment of recurrent grade II and III gliomas, and they report the effects of this treatment on overall survival, progression-free survival, quality of life, toxicity, and neurocognitive function. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trialWe found no evidence of improved overall survival with bevacizumab and temozolomide combination treatment versus temozolomide monotherapy. The findings from this study provide no support for further phase 3 studies on the role of bevacizumab in this disease. Full-Text PDF

Non-invasive determination of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status in glioblastoma (GBM) using magnetic resonance imaging (MRI).

2051Background: MGMT promoter methylation is associated with better prognosis and increased benefit from temozolomide in patients with GBM. The methylation status of the MGMT promoter is typically ...

Regulation of Integrated Stress Response Sensitizes U87MG Glioblastoma Cells to Temozolomide Through the Mitochondrial Apoptosis Pathway.

Glioblastomas are the most frequently diagnosed and worst primary malignancy of the central nervous system, with very poor prognosis. The first-line antiglioma drug temozolomide shows decreasing therapeutic efficacy as treatment progresses. As the integrated stress response (ISR) may be a resistance factor and severe stress might transform the protective effect of the ISR into a damage effect, pharmacological regulation of ISR may be an effective way to sensitize glioma to temozolomide. The aim of the present study was to investigate the mechanisms of the ISR in regulating the therapeutic effect of temozolomide in the human glioblastoma multiforme cell line U87MG. Cultured U87MG cells were treated with temozolomide and PCR array was used to screen key factors in the response to treatment. Cells were co-treated with temozolomide and the eIF2α phosphatase inhibitor salubrinal, and cell apoptosis was measured. Combination treatment with temozolomide and salubrinal had a synergistic effect on cell viability. Salubrinal could upregulate the expression of ATF4, a key factor in the ISR, and enhance temozolomide-induced apoptosis. ATF4 transcriptionally regulated expression of the BH3-ONLY protein NOXA, thus inducing mitochondrial apoptosis. These findings suggest that ISR and ATF4 are involved in the death crosstalk between the endoplasmic reticulum and mitochondria and might be a potential target to enhance the therapeutic effect of temozolomide in patients with glioblastoma multiforme. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Interim Results of a Phase II Study of Hypofractionated Radiotherapy with Concurrent Temozolomide Followed by Adjuvant Temozolomide in Patients over 70 Years Old with Newly Diagnosed Glioblastoma

Objective: In this phase II study, we investigate clinical outcomes and tolerability of hypofractionated radiotherapy (HRT) combined with temozolomide (TMZ) to treat elderly patients with glioblastoma (GBM). Methods: Patients 70 years of age or older with newly diagnosed GBM received HRT to a dose of 34 Gy given in ten fractions over 2 weeks, delivered with concurrent and adjuvant TMZ. Results: In this interim analysis, ten patients were enrolled on trial from 12/1/2015 to 4/5/2017. With a median follow-up of 9 months (range 3–12 months), median progression-free survival (PFS) was 6 months. The median overall survival (OS) has not been reached. Estimated 1-year OS and PFS rates were 53.3 and 44.4%, respectively. All patients completed the full course of RT, with no patients developing grade 3 or higher adverse events from treatment. Conclusions: The preliminary results of our phase II trial suggest HRT delivered over 2 weeks with concurrent and adjuvant TMZ is well tolerated in elderly patients with GBM without compromising clinical outcomes.

EP-1206: Outcomes of SIB-IMRT with concurrent temozolomide in patients with glioblastoma multiforme

EP-1206: Outcomes of SIB-IMRT with concurrent temozolomide in patients with glioblastoma multiforme

A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors such as veliparib are potent sensitizing agents and have been safely combined with DNA-damaging agents such as temozolomide. The sensitizing effects of PARP inhibitors are magnified when cells harbor DNA repair defects. A single-arm, open-label, phase 2 study was performed to investigate the disease control rate (DCR) after 2 cycles of veliparib plus temozolomide in patients with metastatic colorectal cancer (mCRC) refractory to all standard therapies. Fifty patients received temozolomide (150 mg/m2 /d) on days 1 to 5 and veliparib (40 mg twice daily) on days 1 to 7 of each 28-day cycle. Another 5 patients with mismatch repair-deficient (dMMR) tumors were also enrolled. Twenty additional patients were then treated with temozolomide at 200 mg/m2 /d. Archived tumor specimens were used for immunohistochemistry to assess mismatch repair, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and O(6)-methylguanine-DNA methyltransferase (MGMT) protein expression levels. The combination was well tolerated, although some patients required dose reductions for myelosuppression. The primary endpoint was successfully met with a DCR of 24% and 2 confirmed partial responses. The median progression-free survival was 1.8 months, and the median overall survival was 6.6 months. PTEN protein expression and MGMT protein expression were not predictors of DCR. There was also a suggestion of worse outcomes for patients with dMMR tumors. In this heavily pretreated mCRC population, a combination of veliparib and temozolomide was well tolerated with temozolomide doses up to 200 mg/m2 /d, and it was clinically active. PARP inhibitor-based therapy merits further exploration in patients with mCRC. Cancer 2018;124:2337-46. © 2018 American Cancer Society.

Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma

Tumor-treating fields (TTFields) therapy improves both progression-free and overall survival in patients with glioblastoma. There is a need to assess the influence of TTFields on patients' health-related quality of life (HRQoL). To examine the association of TTFields therapy with progression-free survival and HRQoL among patients with glioblastoma. This secondary analysis of EF-14, a phase 3 randomized clinical trial, compares TTFields and temozolomide or temozolomide alone in 695 patients with glioblastoma after completion of radiochemotherapy. Patients with glioblastoma were randomized 2:1 to combined treatment with TTFields and temozolomide or temozolomide alone. The study was conducted from July 2009 until November 2014, and patients were followed up through December 2016. Temozolomide, 150 to 200 mg/m2/d, was given for 5 days during each 28-day cycle. TTFields were delivered continuously via 4 transducer arrays placed on the shaved scalp of patients and were connected to a portable medical device. Primary study end point was progression-free survival; HRQoL was a predefined secondary end point, measured with questionnaires at baseline and every 3 months thereafter. Mean changes from baseline scores were evaluated, as well as scores over time. Deterioration-free survival and time to deterioration were assessed for each of 9 preselected scales and items. Of the 695 patients in the study, 639 (91.9%) completed the baseline HRQoL questionnaire. Of these patients, 437 (68.4%) were men; mean (SD) age, 54.8 (11.5) years. Health-related quality of life did not differ significantly between treatment arms except for itchy skin. Deterioration-free survival was significantly longer with TTFields for global health (4.8 vs 3.3 months; P < .01); physical (5.1 vs 3.7 months; P < .01) and emotional functioning (5.3 vs 3.9 months; P < .01); pain (5.6 vs 3.6 months; P < .01); and leg weakness (5.6 vs 3.9 months; P < .01), likely related to improved progression-free survival. Time to deterioration, reflecting the influence of treatment, did not differ significantly except for itchy skin (TTFields worse; 8.2 vs 14.4 months; P < .001) and pain (TTFields improved; 13.4 vs 12.1 months; P < .01). Role, social, and physical functioning were not affected by TTFields. The addition of TTFields to standard treatment with temozolomide for patients with glioblastoma results in improved survival without a negative influence on HRQoL except for more itchy skin, an expected consequence from the transducer arrays. clinicaltrials.gov Identifier: NCT00916409.

Safety of trifluridine/tipiracil (TAS-102) in combination with temozolomide for metastatic neuroendocrine tumors.

TPS549 Background: Low and intermediate grade neuroendocrine tumors (NETs) are incurable once they metastasize. Cytoreductive surgery and locoregional therapies play an important role in their management, but ultimately most patients are treated with systemic therapies. In clinical studies, combination of temozolomide (TMZ) and capecitabine (CAP) demonstrated significant response rates (&gt; 50%) in patients with advanced pancreatic NETs. Trifluridine/tipiracil (FTD/TPI), also known as TAS-102, is a new anti-metabolite agent that is non-cross resistant with 5-fluorouracil (5-FU) and CAP and that has a different toxicity profile from CAP. In clinical trials, FTD/TPI has been associated with limited toxicities in patients with chemotherapy refractory (including 5-FU and CAP) metastatic colorectal cancer. Given that CAP has demonstrated activity in metastatic NETs, we hypothesize that FTD/TPI in combination with TMZ will be well tolerated and will be efficacious in metastatic NETs. Methods: This is a two-part investigator-initiated phase IB clinical trial (NCT02943733). Part 1 is a dose escalation portion of the study that will determine maximum tolerated doses of FTD/TPI administered in combination with TMZ in patients with advanced NETs. Patients with low and intermediate grade NETs of any origin are eligible for part 1. This part follows a classical “3+3” design to establish the phase 2 doses. Both drugs are oral agents that are administered on a 28 day cycle. FTD/TPI is taken twice a day on days 1-5 and days 8-12. TMZ is taken daily on days 8-12. This schedule was selected based on the pre-clinical data demonstrating schedule-dependent synergism between 5-FU and TMZ. Because of concern for overlapping bone marrow toxicities between the two agents, TMZ is started at the dose of 100 mg/m2 and escalated to a goal dose of 200mg/m2 daily if no dose limiting toxicities are observed. FTD/TPI is started at a goal dose of 35 mg/m2. Part 2 of the study will enroll estimated 15 patients with metastatic pancreatic NETs. Primary endpoint of part 2 is overall response rate, and secondary endpoints are progression free survival, disease control rate and overall survival. Part 1 of the trial is currently open to enrollment. Clinical trial information: NCT02943733.

Hypofractionated intensity-modulated radiotherapy using simultaneous integrated boost technique with concurrent and adjuvant temozolomide for glioblastoma.

We assessed the therapeutic efficacy of combined hypofractionated intensity-modulated radiotherapy with temozolomide in patients with primary glioblastoma. Thirty-nine patients with histologically confirmed glioblastoma were accrued. Using the simultaneous integrated boost technique, a dose of 50 Gy in 5-Gy fractions was applied to the gross tumor volume, together with 40 Gy in 4-Gy fractions and 30 Gy in 3-Gy fractions to the 1- and 2-cm margins from the gross tumor volume, respectively. Patients were also treated with concurrent temozolomide during intensity-modulated radiotherapy, followed by six cycles of adjuvant temozolomide. Median follow-up was 16.8 months (range, 4.3-54.3). Tumor progression was observed in 28 patients (71.8%), and the median time to progression was 6.8 months. Median survival was 16.8 months, and it was affected significantly by the extent of surgery. During adjuvant temozolomide treatment, 3 patients (9.7%) developed grade 3-4 hematologic or hepatic toxicity. Radiation necrosis developed in 7 patients (17.9%) and massive necrosis, requiring emergency surgery, in 1 patient (2.6%). The regimen of hypofractionated intensity-modulated radiotherapy with temozolomide showed a relatively good outcome in patients with glioblastoma. Further studies are required to define the optimal fraction size for glioblastoma using this highly sophisticated radiation technique.

The effect of an adenosine A2A agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma

BackgroundThe blood–brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A2A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A2A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma.MethodsPatients scheduled for a clinically indicated surgery for recurrent glioblastoma were eligible. Microdialysis catheters (MDC) were placed intraoperatively, and the positions were documented radiographically. On post-operative day #1, patients received oral temozolomide (150 mg/m2). On day #2, 60 min after oral temozolomide, patients received one intravenous dose of regadenoson (0.4 mg). Blood and MDC samples were collected to determine temozolomide concentrations.ResultsSix patients were enrolled. Five patients had no complications from the MDC placement or regadenoson and had successful collection of blood and dialysate samples. The mean plasma AUC was 16.4 ± 1.4 h µg/ml for temozolomide alone and 16.6 ± 2.87 h µg/ml with addition of regadenoson. The mean dialysate AUC was 2.9 ± 1.2 h µg/ml with temozolomide alone and 3.0 ± 1.7 h µg/ml with regadenoson. The mean brain:plasma AUC ratio was 18.0 ± 7.8 and 19.1 ± 10.7% for temozolomide alone and with regadenoson respectively. Peak concentration and Tmax in brain were not significantly different.ConclusionsAlthough previously shown to be efficacious in rodents to increase varied size agents to cross the BBB, our data suggest that regadenoson does not increase temozolomide concentrations in brain. Further studies exploring alternative doses and schedules are needed; as transiently disrupting the BBB to facilitate drug entry is of critical importance in neuro-oncology.

Pyrosequencing Analysis of MGMT Promoter Methylation in Meningioma.

Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a well-established predictor of response to the DNA-alkylating agent temozolomide in patients with glioblastoma. Pyrosequencing analysis was used to determine the MGMT promoter methylation status in 61 meningiomas, to clarify whether it might have a predictive role. Only two tumors (3%) had a mean methylation frequency higher than the cut-off value of 10% for the four CpG sites examined. The methylation of the MGMT promoter is uncommon, or occurs at a low frequency in meningiomas. There is no convincing rationale to test such tumors for their MGMT methylation status in a clinical setting.

PARADIGM-2: Two parallel phase I studies of olaparib and radiotherapy or olaparib and radiotherapy plus temozolomide in patients with newly diagnosed glioblastoma, with treatment stratified by MGMT status

Glioblastoma has a dismal prognosis and molecular targeted agents have failed to improve outcomes to date. PARADIGM-2 is a phase I dose escalation study evaluating olaparib plus radiotherapy ± temozolomide in newly diagnosed glioblastoma, using MGMT methylation status to stratify patients and inform treatment schedules.

Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O6-methylguanine DNA methyltransferase as a biomarker for response.

Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O6-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progression free survival (mPFS) was 13.0 months (95% CI: 5.6-17.0) and median overall survival (mOS) 29.3 months (95% CI 17.7 - 45.3). Among evaluable patients, there were 11 (38%) partial responses, 15 (52%) stable disease, and 3 (10%) progressive disease for a disease control rate of 90%. A higher rate of partial responses occurred in patients whose tumors had low levels of MGMT expression (63%) compared to intermediate-high (17%) (p=0.19). Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology. We observed a trend towards increased response rate, median PFS, and median OS in patients whose tumors had low MGMT protein expression.

Indoleamine 2,3-dioxygenase and survivin peptide vaccine combined with temozolomide in metastatic melanoma.

Indoleamine 2,3-dioxygenase (IDO) and survivin have been identified as potential targets for cancer vaccination. In this phase II study a vaccine using the peptides Sur1M2 and IDO5 was combined with the chemotherapy temozolomide (TMZ) for treatment of metastatic melanoma patients. The aim was to simultaneously target several immune inhibiting mechanisms and the highly malignant cells expressing survivin. HLA-A2 positive patients with advanced malignant melanoma were treated biweekly with 150 mg/m2 TMZ daily for 7 days followed by subcutaneous vaccination with 250 µg of each peptide in 500 µL Montanide solution at day 8. Granulocyte-macrophage colony-stimulating factor was used as an adjuvant and topical imiquimod was applied prior to vaccination. Treatment was continued until disease progression. Clinical response was evaluated by PET-CT and immunological outcome was assessed by ELISPOT and flow cytometry. In total, 17 patients were treated with a clinical benefit rate of 18% including one patient with partial tumor regression. Immune analyses revealed a vaccine specific response in 8 (67%) of 12 patients tested, a significant decrease in the frequency of CD4+ T-cells during treatment, a tendency towards decreasing frequencies of naïve CD4+ and CD8+ T-cells, and increasing frequencies of memory CD4+ and CD8+ T-cells. These results demonstrate that vaccine-induced immunity towards survivin and IDO-derived peptides can be achieved in combination with TMZ in patients mainly suffering from grade M1c melanoma including patients with brain metastases. A significant clinical activity could not be proven in this small study and a larger setup is needed to properly assess clinical efficacy.

420TiP - Phase 1b/2 study to assess the safety, tolerability, and clinical activity of BGB-290 in combination with temozolomide in patients with locally advanced or metastatic solid tumors

420TiP - Phase 1b/2 study to assess the safety, tolerability, and clinical activity of BGB-290 in combination with temozolomide in patients with locally advanced or metastatic solid tumors

Abstract CT048: Phase 1/2 study of olaparib tablets and temozolomide in patients with small cell lung cancer (SCLC) following failure of prior chemotherapy

Abstract Background: SCLC is an aggressive high-grade neuroendocrine malignancy. While SCLC is often highly sensitive to first line platinum based chemotherapy, response rates to second line cytotoxic chemotherapy range from approximately 10-30%. Inhibition of poly(ADP-ribose) polymerase (PARP) by the PARP inhibitor olaparib (O) has shown activity in SCLC in preclinical studies, though it does not confer PFS or OS benefit in the maintenance setting as monotherapy (Ahmed et al., 2016). Temozolomide (T) is an alkylating agent with modest single agent activity (ORR 22% in the second line setting; Pietanza et al., 2012), and may synergize with PARP inhibitors. Methods: This ongoing phase 1/2 trial of combination O/T in adults with SCLC (NCT02446704) enrolled patients with histologically or cytologically confirmed incurable SCLC which had progressed following at least one prior platinum-based chemotherapy. O (tablet formulation) and T were administered orally on days 1-7 of 21-day cycles at escalating doses using a standard 3+3 design in the phase 1 portion, with a primary objective of determining the recommended phase 2 dose (RP2D). Response assessments were performed every 6 weeks. In parallel, patient derived xenografts (PDXs) were generated from biopsies and circulating tumor cells (CTCs) from a subset of patients both prior to O/T and at the time of acquired resistance. O/T activity was assessed in vivo in PDXs and in short term cultures. Results: In the phase 1 portion, 13 patients were enrolled to four escalating dose levels. No dose limiting toxicities or grade 4-5 toxicities were observed. The most common grade 3 related toxicities were neutropenia (38%), anemia (15%) and thrombocytopenia (15%). O 200 mg BID and T 75 mg/m2 QD was selected as the RP2D. There were 6 confirmed partial responses (ORR 46%) and responses were seen at all dose levels. The median progression free survival was 5.6 months and median duration of response was 3.4 months. In PDXs, the depth and duration of responses of models derived pre-O/T mirrored those of the corresponding patients. Most pre-treatment models were more sensitive to combination O/T than to either O or T alone. Models derived post-progression were highly resistant to O/T. Further testing to identify biomarkers of response and resistance is ongoing. Conclusions: O/T is well tolerated in patients with SCLC and shows promising clinical activity in a phase 1 study. PDXs derived from CTCs provide a powerful platform for performing co-clinical trials and modeling acquired resistance. Additional correlative studies will be presented. Citation Format: Anna F. Farago, Benjamin J. Drapkin, Allison Charles, Beow Yeap, Rebecca S. Heist, Christopher G. Azzoli, David M. Jackman, David A. Barbie, Edwin Choy, Lecia V. Sequist, Shyamala Maheswaran, Daniel A. Haber, Aaron N. Hata, Nicholas Dyson, Alice T. Shaw. Phase 1/2 study of olaparib tablets and temozolomide in patients with small cell lung cancer (SCLC) following failure of prior chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT048. doi:10.1158/1538-7445.AM2017-CT048

A search for the "Goldilocks zone" with regard to the optimal duration of adjuvant temozolomide in patients with glioblastoma.

A search for the "Goldilocks zone" with regard to the optimal duration of adjuvant temozolomide in patients with glioblastoma.

A two-part safety and exploratory efficacy randomized double-blind, placebo-controlled study of a 1:1 ratio of the cannabinoids cannabidiol and delta-9-tetrahydrocannabinol (CBD:THC) plus dose-intense temozolomide in patients with recurrent glioblastoma multiforme (GBM).

2046 Background: Several plant-derived cannabinoids have shown efficacy in animal models of GBM, particularly when co-administered with temozolomide, a commonly-used treatment in both primary and recurrent disease. Methods: We conducted a two-part study in patients with recurrent GBM following standard chemo-radiotherapy treatment as described by Stupp et al. In Part 1 of the study, 6 patients were treated to an MTD of 1:1 CBD:THC oro-mucosal spray, as an adjunct to dose-intense temozolomide (DIT), to assess the safety of the combination. Part 2 was a double blind, randomized, placebo-controlled study in a planned 20 patients receiving either their individualized dose of 1:1 CBD:THC or placebo plus DIT. The primary endpoint was tolerability of 1:1 CBD:THC plus temozolomide. Results: There were no Grade 3 or 4 toxicities in Part 1 of the study. In Part 2, 12 patients were randomized to CBD:THC and 9 to placebo. Mean age was 58 years in both treatment groups, but there were more males in the placebo group (5 of 12 and 8 of 9, respectively). Baseline median Karnofsky score was 90 in both groups and median time from diagnosis of recurrence to start of treatment (day 1) was similar (3.6 and 3.0 weeks in the CBD:THC and placebo group, respectively). The median number of days of dosing with CBD:THC or placebo was similar (155 days [range: 50-356] and 134 days [range: 13-359]). Median survival in the placebo group was 369 days, and &gt; 550 days in the CBD:THC treatment group (NS) and 1 year survival was 83% and 56% in the CBD:THC and placebo groups, respectively (p = 0.042). PFS6 was 42% in the CBD:THC group and 33% in the placebo group (NS). Overall, the commonest treatment related toxicities were dizziness (in 11/18 patients) and nausea (in 7/18 patients). Results of biomarker analyses are awaited. Conclusions: This randomized study provides preliminary evidence that 1:1 CBD:THC offers some efficacy in patients with recurrent GBM when used as an adjunct to dose-intense temozolomide and confirms the safety and feasibility of individualized dosing. Clinical trial information: NCT01812603.

OS07.3 Nivolumab in Combination With Radiotherapy With or Without Temozolomide in Patients With Newly Diagnosed Glioblastoma: Updated Results From CheckMate 143

OS07.3 Nivolumab in Combination With Radiotherapy With or Without Temozolomide in Patients With Newly Diagnosed Glioblastoma: Updated Results From CheckMate 143