Neurologic Assessment In Neuro-Oncology Scale Research Articles

High-Dose Methotrexate Containing Induction Chemotherapy Followed By Nivolumab Consolidation in Older (≥ 65) Patients with Previously Untreated Primary CNS Lymphoma

Introduction: High-dose methotrexate (HD-MTX)-containing chemotherapy followed by either autologous stem cell transplant (ASCT) or whole-brain irradiation (WBI) is widely considered the standard for primary CNS lymphoma (PCNSL) treatment. However, many older frail patients with PCNSL are unable to undergo ASCT or WBI due to increased risk of treatment-related toxicity, such as infections and neurotoxicity. Without consolidation, survival outcomes are significantly worse, with a 3-year progression free survival (PFS) rate of ~ 30%. Therefore, novel therapeutic approaches are urgently needed for older PCNSL patients. Recently, nivolumab, an anti-PD1 antibody, showed promising clinical activities in relapsed/refractory PCNSL, and we hypothesized that addition of nivolumab in the frontline setting would be safe and improve survival outcomes of older PCNSL patients who are deemed poor candidates for ASCT or WBI. Methods: In this phase 1/1B single-arm multicenter study, patients ≥ 65, who were deemed poor candidates for ASCT and WBI, with previously untreated PCNSL received at least 3 cycles of HD-MTX-containing chemotherapy followed by nivolumab consolidation for 6 cycles (NCT 04022980). Patients with systemic lymphoma or known ocular involvement were excluded from the study. Stage 1 was designed to evaluate the safety of nivolumab consolidation after HD-MTX-containing induction chemotherapy. A 3+3 design was used as safety run-in, initiating 6 patients on nivolumab at the FDA-approved single-agent dose and monitoring for dose-limiting toxicities (DLTs) during Cycle 1. If less than 2 out of 6 subjects experienced a DLT, then the stage 2 part of study would initiate to evaluate the efficacy of nivolumab consolidation in terms of the 2-year PFS. The patient's neurological function was assessed at baseline and throughout the study follow-up using the Neurologic Assessment in Neuro-Oncology (NANO) scale. Results: A total of 14 patients enrolled in the study between April 2020 and December 2022 at 4 US sites. In 14 evaluable patients who underwent the study treatment, the median age was 72 years (range, 65-79), 71% patients were female, and 35% patients had ECOG score of 2 or 3. Variations of the following regimens were used for induction: 43% R-MPV (rituximab, methotrexate, procarbazine, and vincristine) (43%), 29% MRT (methotrexate, rituximab, and temozolomide), 21% MR (methotrexate and rituximab), and 7% MATRix (methotrexate, cytarabine, thiotepa, and rituximab). After induction, 58% achieved a complete response (CR), 33% achieved a partial response (PR), and 8% had a stable disease (SD). Patients received a median of 6 cycles of nivolumab consolidation. Patients who received at least 1 cycle of nivolumab consolidation achieved an overall response rate of 83% with a CR rate of 75%. With a median follow-up duration of 18 months, the 1-year overall survival (OS) and PFS rates were 91.7% and 66.1%, respectively. No DLTs were observed during Cycle 1 of nivolumab consolidation in Stage 1. The most common grade ≥ 3 Adverse Events (AEs) associated with nivolumab consolidation included neutropenia (14%) and fatigue (7%). One patient (7%) developed a grade 4 Stevens-Johnson syndrome associated with sepsis and acute kidney injury, requiring discontinuation of nivolumab after Cycle 1. Conclusion: The current study demonstrates encouraging safety and clinical outcomes of nivolumab consolidation in older PCNSL patients who are deemed poor candidates for ASCT or WBI. No DLT was observed during the safety run-in phase, and there was no unexpected toxicity associated with nivolumab although 1 patient discontinued the study treatment due to Stevens-Johnson syndrome, a rare but known AE associated with nivolumab, after Cycle 1. Overall, nivolumab consolidation was associated with favorable survival rates in a group of patients with poor-risk PCNSL. We are in the process of identifying various clinical and biological factors, including 9p24.1 copy number alteration, in association with the response to nivolumab consolidation. Furthermore, changes in the neurological function based on the NANO scale assessed before and after the nivolumab consolidation are being analyzed.

P11.63.B VALIDATING THE NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN CLINICAL PRACTICE: A MULTI-CENTER PROSPECTIVE STUDY IN PATIENTS WITH GLIOBLASTOMA

Abstract BACKGROUND The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in patients with brain tumors and complement radiographic assessment in defining overall outcomes. The scale has been incorporated in clinical trials, however, real-world use of the NANO scale to drive clinical decision-making and the predictive value of the NANO scale to determine overall survival remains unclear in glioblastoma. MATERIAL AND METHODS We report on an ongoing multi-center study of prospective NANO score collection to evaluate neurologic function in patients with glioblastoma, seen at Dana-Farber Cancer Institute (DFCI) and Sunnybrook Health Sciences Center (SHSC). Patient demographics, tumor histology, molecular status, treatment history, and progression dates are being captured. NANO score, Karnofsky performance status (KPS) and corticosteroid dose are collected at prespecified time points (prior to start of therapy, and during each subsequent MRI visit). Changes in the NANO score will be correlated to overall survival and subgroup analyses will be performed for specific domains of the NANO scale. Statistical analyses including descriptive data analysis and generalized linear models will be performed using R (version 3.4.3). RESULTS Since June 2020, 145 patients have been enrolled in this study across the two sites including 90 (62%) with ≥2 follow-up visits. 129 patients had baseline post-operative NANOs captured, with 45 (35%) patients having no deficits in any NANO domain at baseline. All patients with intact baseline NANO had a KPS of 80 or above. Adaptation to a virtual platform for NANO (vNANO) allowed for improved recruitment and follow-up of patients. Validation of vNANO is being performed in a subset of this population. Our interim analysis will be presented at the 2023 EANO meeting. CONCLUSION Evaluation of neurologic function by NANO is feasible in both an in-person and virtual framework in a prospective multi-center study in patients with glioblastoma. NANO is able to objectively track neurologic function throughout disease course in glioblastoma. Integration of vNANO may allow for reduced clinical visits and improve access to specialized care for patients in geographically remote locations.

LONGITUDINAL NEUROLOGICAL ASSESSMENTS IN BRAIN TUMOR PATIENTS: CORRELATION BETWEEN NANO DOMAINS AND PERFORMANCE STATUS

Abstract The Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) performance status are clinician-reported outcomes critical in guiding management and prognostication in patients with primary brain tumors as they can reflect longitudinal functional changes. However, they are subjective. The Neurologic Assessment in Neuro-Oncology (NANO) scale is a metric with specific neurological domains that was subsequently developed to provide an objective standardized measure of the neurologic functional status of patients, but how longitudinal changes in NANO scale relate to KPS or ECOG scores is unknown. METHODS: A linear mixed model analysis involving 111 patients with primary brain tumors was performed. RESULTS: Statistically significant associations were identified between changes in specific NANO domains and KPS or ECOG scores. After controlling for time course both in univariable and multivariable analyses, worsening scores in gait, language and behavior domains showed significant association with decreased KPS. Gait and behavior were demonstrated to be significantly associated with ECOG both in univariable and multivariable analyses. CONCLUSIONS: The neurologic status of patients with a primary brain tumor is closely related to their performance status. In particular, the patient’s cognitive status and mobility have the greatest impact on their functional status and therefore their prognosis. Interventions and supportive care targeting these domains of function may help improve the outcomes of patients with brain tumors.

OTHR-08. Pediatric Neurologic Assessment in Neuro-oncology (pNANO) Scale: A tool to assess neurologic function for Response Assessment in Neuro-oncology (RAPNO)

Background: The Neurologic Assessment in Neuro-Oncology (NANO) scale, a standardized metric to objectively measure neurologic function in adult brain tumor patients, complements radiographic assessment in evaluating outcomes of neuro-oncology patients in clinical trials and clinical practice. Currently, there is no standardized measure for neurologic function in pediatric neuro-oncology patients despite their distinct clinical presentations and tumor locations. Therefore, we developed a dedicated pediatric NANO (pNANO) scale. Methods: An international group of pediatric neurologists and adult and pediatric neuro-oncologists convened bi-weekly over 5 months to draft the pNANO scale as an objective and quantifiable measure of neurologic function in children that can be administered during routine examination by pediatric-trained providers of any sub-specialty and be utilized together with other indicators to assess response in clinical trials. Results: Ten relevant domains of neurologic function were identified based on common pediatric brain tumor locations: gait, strength, cerebellar function, visual fields, visual acuity, facial strength, level of consciousness, extraocular movements, dysarthria and dysphagia. For each domain, developmental age appropriate levels of function were defined and categorized. Each domain, based on direct observation and testing during any routine neurological exam, can be used for longitudinal monitoring. Conclusions: The pNANO scale has been developed and aims to provide an objective metric of neurologic function for pediatric brain tumor patients. This scale will be tested for reliability, feasibility and inter-observer variability. Consistent evaluation of neurologic function using pNANO along with radiographic assessment will enable more comprehensive and standardized response assessment in pediatric neuro-oncology patients enrolled in clinical trials.

Correlation between Response Assessment in Neuro-Oncology (RANO) Criteria and Clinical Outcome in Patients with Brain Tumor

Response assessment in neuro-oncology (RANO) criteria was established to improve the assessment of tumor response and provide guidance on the assessment of response and endpoints in neuro-oncology clinical trials. Neurologic assessment in neuro-oncology (NANO) scale is an instrument used for assessing neurological function objectively and practical in intracranial tumor patients. This study aimed to determine the association between RANO criteria with clinical outcome measured by NANO scale in intracranial tumors patients. There were 36 intracranial tumor patients that were studied in Haji Adam Malik General Hospital Medan. The RANO criteria were obtained by comparing the size of the enhanced lesion using Computed Tomography (CT) scan within an interval of a minimum of four weeks of treatment. NANO scale is a quantifiable evaluation of nine relevant neurologic domains based on examination. The NANO scale included gait, strength, ataxia, sensation, visual fields, facial strength, language, level of consciousness, and behavior as assessed domains from the medical record. We analyzed the correlation between the RANO criteria and NANO scale score using the Spearman correlation test. There were 19 males and 17 females. The mean age was 45.22±9.68 years. There were 20 patients (55.6%) with meningioma, 11 patients (30.6%) with glioma, 3 patients (8.3%) with brain metastase, and 2 patients (5.6%) with craniopharyngioma. The mean NANO scale scores for stable and progressive RANO criteria were 4.29±2.02 and 7.88±2.99, respectively. There was a significant correlation between RANO criteria and NANO scale score in patients with intracranial tumor (r = 0.468; p = 0.004). Patients with stable RANO had lower NANO scale scores indicating better response to treatment and clinical outcome.

The Prognostic Value of NANO Scale Assessment in IDH-Wild-Type Glioblastoma Patients

BackgroundIDH-wild-type glioblastoma (GBM) is the most frequent brain-derived malignancy. Despite intense research efforts, it is still associated with a very poor prognosis. Several parameters were identified as prognostic, including general physical performance. In neuro-oncology (NO), special emphasis is put on focal deficits and cognitive (dys-)function. The Neurologic Assessment in Neuro-Oncology (NANO) scale was proposed in order to standardize the assessment of neurological performance in NO. This study evaluated whether NANO scale assessment provides prognostic information in a standardized collective of GBM patients.MethodsThe records of all GBM patients treated between 2014 and 2019 at our facility were retrospectively screened. Inclusion criteria were age over 18 years, at least 3 months postoperative follow-up, and preoperative and postoperative cranial magnetic resonance imaging. The NANO scale was assessed pre- and postoperatively as well as at 3 months follow-up. Univariate and multivariate survival analyses were carried to investigate the prognostic value.ResultsOne hundred and thirty-one patients were included. In univariate analysis, poor postoperative neurological performance (HR 1.13, p = 0.004), poor neurological performance at 3 months postsurgery (HR 1.37, p < 0.001), and neurological deterioration during follow-up (HR 1.38, p < 0.001), all assessed via the NANO scale, were associated with shorter survival. In multivariate analysis including other prognostic factors such as the extent of resection, adjuvant treatment regimen, or age, NANO scale assessment at 3 months postoperative follow-up was independently associated with survival prediction (HR 1.36, p < 0.001). The optimal NANO scale cutoff for patient stratification was 3.5 points.ConclusionNeurological performance assessment employing the NANO scale might provide prognostic information in patients suffering from GBM.

INNV-40. REAL WORLD INTEGRATION OF THE NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN CLINICAL PRACTICE IN PATIENTS WITH IDH-WT GBM

BACKGROUNDThe neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in patients with brain tumors and complement radiographic assessment in defining overall outcome. The scale has been incorporated in clinical trials. Early data is suggestive of feasibility and that NANO contributes to overall outcome assessment. However, real-world use of the NANO scale to drive clinical-decision making and the predictive value of the NANO scale to determine overall survival remains unclear in IDH-wt GBM.METHODSWe report on an ongoing study using the NANO scale to evaluate neurologic function in patients with IDH-wt GBM, seen at Dana-Farber Cancer Institute (DFCI). Patient demographics, tumor histology and molecular status, treatment history and progression dates are being captured. NANO score, as collected by a built-in scale in our institutional electronic medical record (EMR), functional status (Karnofsky performance status) and corticosteroid dose are collected at prespecified time points (prior to start of therapy, and during each subsequent MRI visit). Changes in the NANO score will be correlated to overall survival. Statistical analyses including descriptive data analysis and generalized linear models will be performed using R (version 3.4.3).RESULTSSince June 2020, 50 patients have been enrolled in this study, including 42 (84%) with ≥2 follow up visits. Study accrual was initially impacted by the COVID-19 pandemic, but adaptation to a virtual platform for NANO allowed for improved recruitment and follow up of patients. Study results will be available for discussion at the 2021 SNO conference.CONCLUSIONSEvaluation of neurologic function by NANO is feasible in a virtual framework in a prospective study in patients with GBM, aided by integration of the scale in our institutional EMR. NANO is able to objectively track neurologic function throughout disease course in IDH-wt GBM.

The Effects of Administrated Dexamethasone on Neurologic Assessment in Neuro-oncology Scale in Patients with Intracranial Tumors

BACKGROUND: In intracranial tumors, glucocorticoids are the main therapy to treat peritumoral edema. Neurologic Assessment in Neuro-Oncology (NANO) score is an instrument that can assess neurological function objectively and practically in patients with intracranial tumors. AIM: This study aims to determine the effect of dexamethasone administration on the NANO score of intracranial tumor patients. METHODS: This study was a pre-experimental study with a pre and post-test design at the H. Adam Malik General Hospital in Medan from March to September 2020. The study population was intracranial tumor patients. The research subject were 37 subjects taken consecutively. Treated with dexamethasone injection, then examined the NANO score before and after receiving dexamethasone injection on days 1, 2, and 3. Statistical analysis with Friedman test. RESULTS: Based on the demographic characteristics of the research subjects, the mean age was 53.29 ± 8.5 years. Most of the research subjects were male (54.1%) while female (45.9%). Most types of intracranial tumors were secondary tumors (59.5%) while primary tumors (40.5%). The significant effect of dexamethasone on NANO score in patients with intracranial tumors (p &lt; 0.001). CONCLUSION: There is an effect of dexamethasone on the NANO score of patients with intracranial tumors.

NCOG-44. NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN A PHASE II STUDY OF PEMBROLIZUMAB OR PEMBROLIZUMAB PLUS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract PURPOSE The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in brain tumor patients to complement radiographic assessment in defining overall outcome. A multicenter, phase 2 study of pembrolizumab with or without bevacizumab in patients with recurrent glioblastoma incorporated the NANO scale as an exploratory endpoint. METHODS Neurologic examination was evaluated at baseline and MRI assessments using the NANO scale until patients came off study. Statistical descriptive data analysis was performed using R (version 3.4.3). Correlation analysis utilized Fisher’s exact test. RESULTS NANO compliance rate was 94% in 80 patients accrued on the study. Of the 80 patients, 7 were missing NANO at baseline visit and were excluded from analysis for NANO response criteria. Fifteen patients did not have end of treatment NANO evaluation. Of 73 patients, 35 (48%) had a normal neurologic examination at baseline by NANO. Strength and language accounted for the majority of changes in neurologic function over the course of study treatment. Eighteen patients (25%) had neurologic progression by NANO, of whom 2 did not have concurrent radiographic progression. Three patients (pembrolizumab plus bevacizumab cohort) had a neurologic response associated with stable disease on MRI. NANO assessment prior to initiation of cycle 3 correlated with RANO response (p=0.011), change in KPS (p=0.002) and dexamethasone requirement (p=0.007) while those with NANO progression at this assessment had worse overall survival (291 vs 324 days), but this trend did not achieve statistical significance (p=0.2). CONCLUSIONS Evaluation of neurologic function by NANO scale was feasible in a multicenter prospective study in patients with GBM with a high compliance rate. The NANO scale objectively tracked stable neurologic function in most patients throughout the trial period and was associated with a trend for survival.

CTIM-32. PHASE II AND BIOMARKER STUDY OF PEMBROLIZUMAB OR PEMBROLIZUMAB PLUS BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA PATIENTS

Abstract PURPOSE Vascular endothelial growth factor (VEGF) is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase 2 study of pembrolizumab, a programmed death-1 (PD-1) blocking antibody alone or with the anti-VEGF antibody bevacizumab in recurrent glioblastoma with detailed analyses of biomarkers and patient neurologic function. METHODS Eighty bevacizumab-naive, recurrent glioblastoma patients were randomized to receive pembrolizumab with bevacizumab (cohort A, n=50) or pembrolizumab monotherapy (cohort B, n=30). The primary endpoint was six-month progression-free survival (PFS-6). Exploratory endpoints included evaluation of tumor PD-L1 expression, TIL density, immune activation gene expression signature and plasma cytokines with outcome. Changes in neurologic function were prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale. RESULTS Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% (95% CI: 16.3, 41.5), median OS was 8.8 months (95% CI: 7.7, 14.2), ORR was 20% and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI: 1.7, 25.4), median OS was 10.3 months (95% CI: 8.5, 12.5) and ORR was 0%. Factors associated with worsened OS included baseline dexamethasone use and increased post-therapy plasma VEGF (cohort A) and wild-type IDH1, unmethylated MGMT and increased baseline PlGF and sVEGFR1 levels (cohort B), but tumor immune markers were not informative. The NANO scale effectively predicted neurologic function. CONCLUSIONS Although well tolerated, pembrolizumab was ineffective both as monotherapy and with bevacizumab for recurrent glioblastoma. Nonetheless, radiographic responses to combinatorial therapy were durable. Baseline dexamethasone use and plasma cytokines but not tumor immunologic biomarkers were associated with outcome. Neurologic function evaluated by the NANO scale contributed to outcome assessment.

The Neurologic Assessment in Neuro-Oncology (NANO) Scale as an Assessment Tool for Survival in Patients With Primary Glioblastoma.

The Neurologic Assessment in Neuro-Oncology (NANO) scale is a standardized objective metric designed to measure neurological function in neuro-oncology. Current neuroradiological evaluation guidelines fail to use specific clinical criteria for progression. To determine if the NANO scale was a reliable assessment tool in glioblastoma (GBM) patients and whether it correlated to survival. Our group performed a retrospective review of all patients with newly diagnosed GBM from January 1, 2010, through December 31, 2012, at our institution. We applied the NANO scale, Karnofsky performance score (KPS), Eastern Cooperative Oncology Group (ECOG) scale, Macdonald criteria, and the Response Assessment in Neuro-Oncology (RANO) criteria to patients at the time of diagnosis as well as at 3, 6, and 12 mo. Initial NANO score was correlated with overall survival at time of presentation. NANO progression was correlated with decreased survival in patients at 6 and 12 mo. A decrease in KPS was associated with survival at 3 and 6 mo, an increase in ECOG score was associated only at 3 mo, and radiological evaluation (RANO and Macdonald) was correlated at 3 and 6 mo. Only the NANO scale was associated with patient survival at 1 yr. NANO progression was the only metric that was linked to decreased overall survival when compared to RANO and Macdonald at 6 and 12 mo. The NANO scale is specific to neuro-oncology and can be used to assess patients with glioma. This retrospective analysis demonstrates the usefulness of the NANO scale in glioblastoma.

Response Assessment in Neuro-Oncology Clinical Trials.

Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in neuro-oncology for which contrast enhancement serves as an imperfect surrogate for tumor volume and is influenced by agents that affect vascular permeability, such as antiangiogenic therapies. In addition, most tumors have a nonenhancing component that can be difficult to accurately quantify. To improve the response assessment in neuro-oncology and to standardize the criteria that are used for different CNS tumors, the Response Assessment in Neuro-Oncology (RANO) working group was established. This multidisciplinary international working group consists of neuro-oncologists, medical oncologists, neuroradiologists, neurosurgeons, radiation oncologists, neuropsychologists, and experts in clinical outcomes assessments, working in collaboration with government and industry to enhance the interpretation of clinical trials. The RANO working group was originally created to update response criteria for high- and low-grade gliomas and to address such issues as pseudoresponse and nonenhancing tumor progression from antiangiogenic therapies, and pseudoprogression from radiochemotherapy. RANO has expanded to include working groups that are focused on other tumors, including brain metastases, leptomeningeal metastases, spine tumors, pediatric brain tumors, and meningiomas, as well as other clinical trial end points, such as clinical outcomes assessments, seizures, corticosteroid use, and positron emission tomography imaging. In an effort to standardize the measurement of neurologic function for clinical assessment, the Neurologic Assessment in Neuro-Oncology scale was drafted. Born out of a workshop conducted by the Jumpstarting Brain Tumor Drug Development Coalition and the US Food and Drug Administration, a standardized brain tumor imaging protocol now exists to reduce variability and improve reliability. Efforts by RANO have been widely accepted and are increasingly being used in neuro-oncology trials, although additional refinements will be needed.

The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria.

The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria define radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specific parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology. An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, inter-observer variability, and feasibility. The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine office visits. The score defines overall response criteria. A prospective, multinational study noted a >90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3-5). The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients.

QOL-07DESCRIPTION OF CLINICAL AND PATIENT REPORTED OUTCOMES ASSESSMENTS FROM A PHASE 3, MULTICENTER, RANDOMIZED TRIAL EVALUATING NIVOLUMAB MONOTHERAPY VERSUS BEVACIZUMAB IN RECURRENT GLIOBLASTOMA: CHECKMATE-143

Advances in therapy for glioblastoma (GBM) have provided limited survival and health-related quality of life (HRQoL) benefit. Symptom management and maintaining HRQoL are important metrics for assessing treatment benefit. To inform on these metrics, both clinician- and patient-reported outcome measures to evaluate HRQoL and neurocognitive impairment were included as exploratory endpoints in the randomized cohort 2 of CHECKMATE-143, evaluating nivolumab monotherapy versus bevacizumab in adult patients with recurrent GBM. Clinician assessment of neurologic function will be done using the Neurologic Assessment in Neuro-Oncology (NANO) scale, which includes nine major domains (gait, strength, ataxia, sensation, visual field, facial strength, language, level of consciousness, and behaviour). The Cogstate assessment, consisting of a computerized battery of neurocognitive tests of approximately 15 minutes in duration, was used to evaluate neurocognitive functioning, cognitive deficits and/or executive functioning at baseline, and on day 1 of weeks 13, 21, 45, and 69, and at the time of treatment discontinuation. Patient-reported HRQoL was determined using the EORTC QLQ-C30, an assessment commonly used in oncology studies and comprising six functional scales (physical functioning, cognitive functioning, emotional functioning, social functioning, role functioning, and global QoL) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and the QLQ-BN20, a brain tumor-specific instrument evaluating four domains (future uncertainty, visual disorder, communication deficit, and motor dysfunction). The standardized EuroQoL-5D will be used for self-assessment of general health status across five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety) and includes a visual analog rating scale. Scoring by using the NANO scale and assessment with the EORTC QLQ-C30, QLQ-BN20 and EQ5D will be done at baseline, weeks 7, 13, and every 8 weeks thereafter until treatment discontinuation. Methodology and baseline information regarding the use of these patient and clinician scales will be reported.