Treatment of recurrent malignant supratentorial gliomas with carboplatin (CBDCA)

Summary Twenty patients with malignant supratentorial gliomas progressing after radiation therapy and chemotherapy with nitrosoureas received intravenous carboplatin, 450 mg/m². Courses of therapy were repeated every four weeks. Therapeutic evaluation was performed monthly using neurologic examination and CT scan of the brain. Of 19 patients evaluable for response, 2 (10%) responded to therapy and 6 (30%) had stable disease. The estimated median time to tumor progression for responding and stable patients was 6 months. Median duration of survival was 6 months for all patients. Of 20 patients evaluable for toxicity, none had renal or auditory toxicity. Side effects consisted of hematologic toxicity in 4 patients (20%): one patient had grade 4 toxicity requiring discontinuation of carboplatin and 3 patients had grade 2–3 toxicity.Abbreviation HECNU 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea     

Treatment of recurrent malignant gliomas with stereotactic intensity modulated radiation therapy

Malignant gliomas are usually refractory to aggressive combined-modality therapy, and the incidence of recurrence and death after treatment is very high. State-of-the-art techniques such as stereotactic intensity-modulated radiation therapy (IMRT) are now available to deliver a high dose of radiation to the tumor with relative preservation of surrounding tissues to achieve optimal tumor coverage with minimal toxicity. We report 10 patients (median age 48 years) with recurrent malignant gliomas that were treated with stereotactic directed IMRT. Initial tumor histologies included one low grade glioma (upgraded to anaplastic astrocytoma at recurrence), four anaplastic astrocytomas, and four glioblastomas multiforme. One patient was originally presumed to have a brain metastasis secondary to renal cell carcinoma but was pathologically confirmed as having glioblastoma multiforme at the time of recurrence. Before recurrence, all patients had been treated with external beam radiation therapy (median 59.7 Gy). All recurrences were confirmed by a subtotal resection (5/10) or by imaging (5/10). The median Karnofsky performance score at the time of IMRT was 80. The median tumor volume was 34.69 cm. Treatment was delivered on a 10-MV linear accelerator with a mini-multileaf collimator, MIMiC, and planned with Peacock/Corvus software. Radiation was delivered in daily fractions of 5 Gy, to a total median dose of 30 Gy at the 71% to 93% median isodose line. Median overall survival time was 10.1 months from the date of stereotactic treatment, with 1- and 2-year survival rates of 50% and 33.3%, respectively. Fractionated stereotactic intensity modulated radiation therapy is a novel technique used in the treatment of recurrent malignant gliomas, which produces results comparable to other currently used stereotactic techniques.     

Treatment of children with recurrent high grade gliomas with a bevacizumab containing regimen

Children with recurrent high grade gliomas (HGG) have a dismal outcome with a median progression free survival (PFS) of 12 weeks. Adults with recurrent HGG treated with irinotecan and bevacizumab reportedly have a 63% response rate and a median PFS of 23 weeks. There is a paucity of corresponding published pediatric data. We retrospectively reviewed the records of patients less than 21 years of age with recurrent or progressive WHO grade 3–4 gliomas who were treated with bevacizumab containing regimens at our institution between January 2006 and September 2008. We identified eight patients. Six out of eight patients received irinotecan, temozolomide and bevacizumab, one patient received irinotecan and bevacizumab, and one patient received CCNU and bevacizumab. Three patients had stable disease for 30–93 weeks. The remaining five patients developed progressive disease within 17 weeks. The median PFS was 15 weeks and the 6-month PFS was 38%. Contrast enhancing disease responded or remained stable in five out of seven patients whereas non-enhancing disease progressed in three out of four patients. New distant non-enhancing lesions developed in three patients. The most common side effects included diarrhea, vomiting, thrombocytopenia and neutropenia. Bevacizumab was well tolerated when used in combination with conventional chemotherapy (irinotecan in most cases). PFS in our cohort was much shorter and the response rate was inferior in this small cohort of patients when compared with published adult data. However, bevacizumab containing regimens might be effective in a subset of pediatric patients, especially those with predominantly contrast-enhancing disease.     

手术联合重组人p53腺病毒注射液治疗复发性恶性胶质瘤的临床研究

目的:探讨手术联合重组人p53腺病毒注射液(rAd-p53)治疗复发性恶性胶质瘤的安全性和有效性。方法:38例复发性恶性胶质瘤患者再次行手术治疗,联合治疗组(手术+rAd-p53)18例患者术中埋放Om-maya囊,术后定期给予rAd-p53,单纯手术组20例患者不接受rAd-p53治疗,两组均随访>1年。结果:联合治疗组6个月生存率66.7%(14/18),1年生存率44.4%(8/18),中位生存期(42.4±3.1)周,较单纯手术组明显提高。联合治疗组6个月Karnofsky评分明显提高,P<0.05。结论:rAd-p53对于复发性恶性胶质瘤安全有效,能延长患者生存期,改善生存质量。     

手术联合重组人p53腺病毒注射液治疗复发性恶性胶质瘤

目的 探讨手术联合重组人p53腺病毒注射液(rAd-p53)治疗复发性恶性胶质瘤的安全性和有效性.方法 38例复发性恶性胶质瘤患者再次行手术治疗.联合治疗组的18例患者术中埋放Ommaya储液囊,将1×1012VP rAd-p53经Ommaya储液囊注入瘤腔,每周1次,4周为1个疗程,连续2～4个疗程.手术组20例患者单纯行手术切除.两组患者均随访1年以上.结果 联合治疗组6个月生存率为66.7%,1年生存率为44.4%,中位生存期为9.7个月,较手术组(7.1个月)明显提高.联合治疗组术后6个月Karnofsky评分为(81.8±15.7)分,较术前明显提高(P＜0.05);术后1年Karnofsky评分为(66.1±17.4)分,明显高于手术组[(53.5±18.2)分,P＜0.05].结论 rAd-p53对于复发性恶性胶质瘤安全有效,能延长患者生存期,改善患者的生活质量.     

Treatment of recurrent gliomas and metastatic brain tumors with a polydrug protocol designed to combat nitrosourea resistance.

PURPOSE: The study was undertaken to evaluate a chemotherapy protocol against recurrent malignant gliomas that was designed to combat presumed chloroethyl-nitrosourea (NU) resistance. PATIENTS AND METHODS: All patients had malignant gliomas and had failed prior therapy. Patients were stratified as having either glioblastoma multiforme (GM) or anaplastic gliomas (AG) and as having failed radiotherapy (RT) only or both RT and chemotherapy. Chemotherapy consisted of six drugs: before lomustine (CCNU), thioguanine (TG), dibromodulcitol (mitolactol; DBD), and procarbazine (PCB) were given to enhance CCNU-induced tumor-cell kill and to reduce alkyltransferase repair of ethylated DNA. A fluorouracil-hydroxyurea (FUHU) combination was given 2 weeks later to kill cells that began to cycle after the challenge of the first four drugs (TPDC-FUHU chemotherapy). RESULTS: Of the 88 assessable patients, 37 had GM, 38 had AG, and 13 had other primary and metastatic brain tumors. For GM patients, 61% had a partial response (PR) or stable disease (SD) for a median of 9.3 months if RT only failed, and 58% had a PR or SD for a median of 5.1 months if they had previously been treated with an NU. For AG patients, 92% had a PR or SD for a median of 15 months if RT only had failed, but only 38% had a PR or SD for a median of 10.6 months if they had been previously treated with a NU. Activity was also seen against other recurrent or progressive primary and metastatic brain tumors. CONCLUSIONS: TDPC-FUHU chemotherapy is a highly effective form of chemotherapy for both recurrent GM and AG patients. This study suggests but does not prove that this combination may be superior to other NU-based treatments for recurrent malignant glioma patients who fail RT. Because of the activity of this chemotherapy, we intend to evaluate more fully this approach in a randomized study.     

手术切除联合间质内缓释化疗治疗复发性脑胶质瘤

目的 探讨外科手术切除与瘤床问质内缓释化疗治疗复发性脑胶质瘤的疗效。方法 对30例复发性恶性脑胶质瘤患者行开颅手术全切除,术中在瘤床植入Vp-16多聚缓释体,用量为100～150mg。随访3～24个月,观察肿瘤再次复发率和患者死亡率,并与以前随访的46例再次手术的恶性脑胶质瘤结果相对比。结果 30例患者均获随访,3个月复发5例(16．7％),死亡2例(6．7％);6个月复发9例(30．0％),死亡6例(20．0％);12个月复发15例(50．0％),死亡12例(40．0％);24个月复发25例(83．3％),死亡21例(70．0％);全部患者均无化疗不良反应。结论 力争手术全切除联合瘤床间质内缓释化疗,可提高药物在瘤灶处的浓度和作用时间,从而提高复发性脑胶质瘤的疗效。     

Role of radiotherapy in recurrent gliomas

Intracranial gliomas account for less than 2% of primary solid tumors in adults, but are among the most frequent causes of death from cancer in children. Their increasing incidence and the weak impact of treatments on the prognosis justify all the efforts expended to improve results. Surgery, radiation therapy (RT) and chemotherapy are proposed as first-line therapy, according to indications and modalities that remain controversial. In this palliative setting, the only consensus is to search for an optimal efficacy/toxicity ratio. Finally, after a very variable duration of local control depending on the histologic type, recurrence is virtually inevitable, with mainly local progression. The prognosis is then generally dismal, with a median survival of less than 6 months. Although re-operation is efficient for the rapid relief of symptoms, it is often rejected. After or in the absence of surgery, different chemotherapy schedules are proposed according to the histologic type and the patient's general status and objective response rates are very limited, except in the case of oligodendrogliomas. Re-irradiation has a rather bad reputation: even as first-line therapy, total doses never exceed 60 Gy in 30 fractions of 2 Gy over six weeks (conventional fractionation). The main reasons are concerns about increasing unacceptable late neurologic complications and the absence of a demonstrated dose-effect beyond this threshold. However, some arguments have led clinicians to consider lifting the ban on re-irradiation. Among adult patients receiving focal RT for low-grade gliomas, late neurologic toxicity was recently evaluated prospectively using a battery of neurocognitive tests. Compared with the initial status, no significant deleterious effects were observed with a follow-up of at least 3 years. In addition, studies on primates demonstrated that the spinal cord was capable of repairing, at least partially, RT-induced injury. There appears to be room for further irradiation: the results of re-irradiation in more than 300 patients have been documented. The techniques used, patient selection and re-irradiation modalities reported were varied: interstitial brachytherapy or intraoperative-RT within the surgical bed, conformal 3D RT, stereotactic-RT delivered in one or several fractions. Treatment efficacy and toxicity endpoints were very heterogeneous. Nevertheless, with a clearly defined prospective assessment, re-irradiation seems possible without any unacceptable clinical neurotoxicity under the following conditions: a good general status (WHO 0-1); at least a one-year disease-free interval; an initial WHO grade 2 or 3 histology with a maximal tumor diameter not exceeding 3 cm. In this very selective setting, re-irradiation is possible at a dose of 30 to 40 Gy, if possible in stereotactic mode, with a hypofractionated schedule (less than 4 Gy/fraction). Median survival exceeding one year is expected, the main endpoint being the control of symptoms and quality of life.     

Treatment of malignant gliomas with interstitial irradiation and hyperthermia.

A Phase I study of interstitial thermoradiotherapy for high-grade supratentorial gliomas has been completed. The objective of this trial was to test the feasibility and toxicity of hyperthermia induced by ferromagnetic implants in the treatment of intracranial tumors. The patient population consisted of 16 males and 12 females, with a median age of 44 years and a median Karnofsky score of 90. Nine patients had anaplastic astrocytoma while 19 had glioblastoma multiforme. Twenty two patients were treated at the time of their initial diagnosis with a course of external beam radiotherapy (median dose 48.4 Gy) followed by an interstitial implant with Ir-192 (median dose 32.7 Gy). Six patients with recurrent tumors received only an interstitial implant (median dose 40 Gy). Median implant volume for all patients was 55.8 cc and median number of treatment catheters implanted per tumor was eighteen. A 60-minute hyperthermia treatment was given through these catheters just before and right after completion of brachytherapy. Time-averaged temperatures of all treatments were computed for sensors located within the core of (> 5 mm from edge of implant), and at the periphery of the implant (outer 5 mm). The percentage of sensors achieving an average temperature > 42 degrees C was 61% and 35%, respectively. Hyperthermia was generally well tolerated; however, there have been 11 minor toxicities, which resolved with conservative management, and one episode of massive edema resulting in the death of a patient. In addition, there were three major complications associated with the surgical implantation of the catheters. Preliminary survival analysis shows that 16 of the 28 patients have died, with a median survival of 20.6 months from diagnosis. We conclude that interstitial hyperthermia of brain tumors with ferromagnetic implants is feasible and carries significant but acceptable morbidity given the extremely poor prognosis of this patient population.     

Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas.

PURPOSE: The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated. RESULTS: A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls. CONCLUSION: This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.     

Response rate and toxicity with aziridinylbenzoquinone in patients with recurrent gliomas. A progress report

Aziridinylbenzoquinone (AZQ), a quinone-containing lipophilic alkylating agent with molecular properties allowing for good penetration through the blood-brain barrier into the central nervous system, was evaluated in a phase II trial for recurrent gliomas patients. Twenty-four patients with computed tomography (CT) scan measurable disease were entered into the trial and received AZQ in doses of a weekly infusion of 15 mg/m2 (group A) and 17.5 mg/m2 (group B). Twenty-two patients were evaluable for both response and toxicity. There were no complete responses in this study. Partial response rates of 23% (3/13) and 11% (1/9) were achieved in group A and group B patients, for a median duration of response of 35 (range 10-106 weeks) and 19 weeks, respectively. The disease was stabilized in five patients from group A and in four patients from group B. Toxicity was mainly hematologic.     

Gamma knife radiosurgery for recurrent gliomas

Objective

In recent years, gamma knife radiosurgery (GKRS) has become increasingly more popular as a salvage treatment modality for patients diagnosed with recurrent gliomas. The goal of GKRS for recurrent glioma patients is to improve survival rates with minimal burden for these patients. The emphasis of this report is on local tumor control (TC), clinical outcome and survival analysis.

Methods

We performed a retrospective analysis of prospectively collected data of all patients who underwent GKRS for gliomas at the Gamma Knife Center Tilburg between 23-09-2002 and 21-05-2015. In total, 94 patients with glioma were treated with GKRS. Two patients were excluded because GKRS was used as a first stage treatment. The other 92 patients were included for analysis.

Results

TC was 37% for all tumors (TC was 50% in LGGs and 27% in HGGs). Local progression (LP) was 46% for all tumors (LP was 31% in LGGs and 58% in HGGs). New distant lesions were seen in 18% of all patients (in 5% of LGG patients and 31% of HGG patients). Median progression-free and overall survival (PFS and OS) for all patients were 10.5 and 34.4 months, respectively. Median PFS was 50.1 and 5.7 months for low and high grade tumors, respectively. Median OS was 86.6 and 12.8 months for low and high grade tumors, respectively. No serious adverse events were noted post-GKRS.

Conclusion

GKRS can safely be used as salvage treatment for recurrent glioma and seems to improve survival rates in (high grade) glioma patients with minimal burden.

     

Bevacizumab in recurrent high-grade pediatric gliomas

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m². Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald''s criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference.     

Treatment of recurrent malignant supratentorial gliomas with the association of carboplatin and etoposide: a phase II study

Thirty one patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosoureafor malignant supratentorial gliomas received a combination of carboplatin (CBDCA) and etoposide(VP16) at tumor progression. Carboplatin and etoposide(CE) were given, each at a dose of 100 mg/m²/day from day 1 to 3. The response was evaluated at each course and a minimum of three courses was required to definite stable patient.Tolerance was evaluated in 31 patients. None had renalor auditory toxicity. Side effects consisted of grade III hematologic toxicity in 6 patients (19%), and grade III hepatic toxicity in one patient. No gradeIV WHO toxicity was observed.All 31 patients could be evaluated for therapeutic response.A partial response was noted in 4 patients during 13, 34 +, 35 + and 51 + weeks. Ten patients had stabledisease after a minimum of 3 courses (19 to 37 weeks). The rate of partial response (PR)and stabilisation (S) was 45% (14/31). The median time to tumor progression (MTTP) for respondingand stable patients was 28 weeks. The median survival time(ST) for the entire group was 45 weeks and over 51 weeks for PR and S patients.     

Toxicity, efficacy, and pharmacology of suramin in adults with recurrent high-grade gliomas.

PURPOSE: To determine the toxicity, efficacy, and pharmacology of suramin in patients with recurrent or progressive recurrent high-grade gliomas. PATIENTS AND METHODS: Fifty adults were to receive suramin. However, if no responses were seen in the first ten patients, the study was to be terminated. A total of 12 patients were enrolled onto this trial. Ten patients had glioblastoma multiforme, and 11 had received prior nitrosoureas. RESULTS: Drug-related toxicities were modest and reversible. Three patients developed grade 3 to 4 neutropenia, constipation, diarrhea, or nausea. No CNS bleeding was observed. Median time to progression was 55 days (range, 17 to 242 days) and median survival was 191 days (range, 42 to 811 days). No partial or complete responses were seen at 12 weeks. However, the clinical outcome of three patients suggests that evidence of suramin activity may be delayed. One patient who "progressed" after 12 weeks of suramin had a subsequent marked reduction in tumor size and has maintained an excellent partial response for over 2 years without other therapy. Two others had disease stabilization and lived for 16 and 27 months. Pharmacokinetics from 11 patients revealed that all reached target suramin concentrations. CONCLUSION: This study demonstrates that suramin is well tolerated by patients with recurrent high-grade gliomas and may have efficacy in this disease. Its pharmacology seems unaffected by anticonvulsants. As a result of this data, suramin and radiation are now being administered concurrently to patients with newly diagnosed glioblastoma multiforme, with survival as the primary outcome.     

Intravenous BCNU and AZQ in patients with recurrent malignant gliomas

Twenty-four patients with recurrent malignant glioma were treated with intravenous BCNU (80 mg/m²/day × 3 days) alternating with AZQ (8 mg/m²/day × 5 days) every 6–8 weeks. Twenty patients received two or more courses of chemotherapy, ten anaplastic astrocytomas (AA), eight glioblastomas (GBM), and two malignant oligodendrogliomas (Oligo). All had prior surgery and irradiation; one had prior chemotherapy. Median age was 37.5 years. The median Zubrod performance status (PS) was 1. Three patients (15%) achieved response status, and 7 (35%) had stable disease with median times to tumor progression (MTP) of 56 wks and 35 wks. MTP for patients with progression was 11 weeks. No GBM was responsive to chemotherapy and none of the ten patients with stable or responsive disease were older than fifty years. Dose limiting toxicity was consisted of thrombocytopenia and leukopenia. Young patients with recurrent AA and good PS appear more likely to respond to alternating BCNU/AZQ chemotherapy. The overall response rate (response plus stable) of 50% was comparable to that of BCNU alone and the hematologic toxicity was cumulative.     

Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas.

PURPOSE: Little progress has been made in the treatment of adult high-grade gliomas over the last two decades, thus necessitating a search for novel therapeutic strategies. Malignant gliomas are vascular or angiogenic tumors, which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors. We present the results of a phase II trial of thalidomide, a putative inhibitor of angiogenesis, in the treatment of adults with previously irradiated, recurrent high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of anaplastic mixed glioma, anaplastic astrocytoma, or glioblastoma multiforme who had radiographic demonstration of tumor progression after standard external-beam radiotherapy with or without chemotherapy were eligible. Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved. Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria. RESULTS: A total of 39 patients were accrued, with 36 patients being assessable for both toxicity and response. Thalidomide was well tolerated, with constipation and sedation being the major toxicities. One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year. There were two objective radiographic partial responses (6%), two minor responses (6%), and 12 patients with stable disease (33%). Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. Changes in serum levels of basic fibroblastic growth factor (bFGF) were correlated with time to tumor progression and overall survival. CONCLUSION: Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high-grade gliomas. Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy. Additionally, studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and/or glioma growth.     

Retrospective study of nivolumab for patients with recurrent high grade gliomas

Introduction

Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS).

Methods

We retrospectively analyzed HGG patients treated with nivolumab in our institution. We included patients with advanced HGG who received nivolumab at their oncologist’s decision. Patients received nivolumab 3 mg/kg every 2 weeks until confirmed progression, intolerable toxicity, death, or physician decision. Radiographic assessments were performed every 8 weeks.

Results

Between April 2015 and October 2017, 50 HGG patients received nivolumab. 43 patients received nivolumab with bevacizumab. 44 patients were bevacizumab refractory and 7 patients received nivolumab monotherapy. All had received prior radiation and chemotherapy. 39 adverse events (AEs) were noted [most commonly fatigue (16%) and constipation (10%)]. 4 (8%) patients experienced grade 3–4 AEs. 36 (72%) patients experienced stable disease (SD) at the 2-month assessment. Median duration of SD was 4.3 months (5.1 months in the bevacizumab naïve, 3.8 months in the bevacizumab refractory). Median PFS was 4.3 months (95% CI 3.5–5.3); median OS was 6.5 months (95% CI 6.0–8.8).

Conclusion

Treatment with nivolumab therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre-treated recurrent HGG.