BackgroundNo treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.MethodsAdult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint.ResultsBetween June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events.ConclusionThe combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.

2034 Background: Patients (pts) with recurrent glioblastoma (rGB) have a poor prognosis, and no treatment option demonstrated to improve survival in a randomized trial. Axitinib (AXI), an oral VEGFR 1-3 inhibitor has demonstrated single agent activity in rGB and reduces the need for corticosteroids (CS). Avelumab (AVE) is a fully human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types. Combination of AXI and AVE may improve the outcome of pts with rGB. Methods: This open-label, dual-strata, single-center phase 2 clinical trial investigated the activity of AXI plus AVE in adult pts with rGB following prior surgery, RT and temozolomide. Pts were stratified according to their baseline use of CS. Pts without baseline need for CS initiated treatment with AXI (5 mg oral BID) plus AVE (10 mg/kg IV Q2W) (cohort-1). Pts in need of CS initiated AXI as a monotherapy; AVE could be added to AXI after 6 wks if the CS dose could be tapered to a physiologic dose level or less (cohort-2). Six-month-PFS served as the primary endpoint (with a prespecified threshold of ≥ 50% for cohort-1) according to Fleming one-stage design. Results: Between Jun 2017 and Aug 2018, 54 pts (27 per cohort) were enrolled (med age 55 y [range 19-75]; 63% male; 91% WHO PS 0-1). All pts in cohort-1 and 16 pts (59%) in cohort-2 received at least 1 dose of AVE. The 6-month-PFS was 18% (95% CI 4-33) in both cohorts. At the time of analysis, 2 pts were progression-free and continuing study treatment. Median OS in cohort-1 and -2 was respectively 26 wks (95% CI 21-32) and 18 wks (95% CI 14-22). No clear relation was found between baseline cognitive functioning (Cogstate subtests) and PFS/OS. The best overall response rate (iRANO) was 41% and 26% respectively for pts in cohort-1 and -2. The most frequent all-grade treatment-related adverse events (TRAE) were dysphonia (67%), lymphopenia (50%), diarrhea (48%), hypertension (48%), and fatigue (46%). The incidence of grade 3-4 TRAE was 30%; there were no grade 5 AE. Conclusions: The combination of AVE plus AXI is sufficiently well tolerated but did not meet the threshold for activity justifying further investigation in an unselected population of patients with rGB. Clinical trial information: NCT03291314.

162 Background: An increasing proportion of advanced melanoma patients (pts), treated with immune checkpoint inhibitors and/or BRAF/MEK-inhibitors, achieve long-term survival. The traumatic experience of melanoma progression, which often involves the brain, puts them at high risk for emotional and neurocognitive function (NCF) disturbances that may negatively impact their HRQoL. Methods: Pts with advanced melanoma (AJCC stages IIIC or IV) who were in remission for at least 1 year after treatment initiation were included in this ongoing single-center therapeutically non-interventional clinical trial. Data on psychosocial outcome and HRQoL were collected using 6 validated questionnaires, a semi-structured psychiatric examination (SSPE) and a computer based neuro-cognitive function (NCF) test. Results: Test results from the first 24 pts (9M/15F; median age 58y (29-87) were analysed. Mean EORTC Global Health Score was significant lower than the European Mean (t[23]=2.713, p= 0.006). The SSPE revealed that all pts reported fear of recurrence; 19 pts (79%) suffered from feelings of insecurity with daily worrying about the disease, associated with a fear of dying. Irritability was a prominent complaint in 18 pts [75%]). Twelve pts (50%) received a message of no hope at diagnosis of metastatic disease which had a persistent major psychological impact. Suicidal ideation occurred in 3 pts (13%), 1 pt (4%) made a suicide attempt (in the absence of depression). Nine pts (38%) reported worrying about their family, 4 pts (17%) had relational problems and 7 pts (29%) had financial problems related to the disease. Despite frequent fatigue complaints, only 4 pts (17%) had mild excessive sleepiness on the Epworth Sleepiness Scale and 9 pts (38%) on the Fatigue Severity Scale. The HADS results indicated a greater occurrence of anxiety compared to depression (NA=10, ND=6). Twenty pts (83%) reported memory complaints, but only 7 pts (29%) had elevated scores on the Cognitive Failure Questionnaire (CFQ). Conclusions: Advanced melanoma survivors are at risk of emotional and neurocognitive disturbances impacting on their HRQoL. Timely detection of psychosocial and neurocognitive problems and adapted care are indicated.

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97 Background: Immunotherapy with the CTLA-4 blocking mAb ipilimumab (IPI) has improved the long-term (>3 y) survival of a subpopulation (15-20%) of patients (pts) with metastatic melanoma. Little is known about the psychosocial outcome and the long-term effects of immune-related adverse events in these survivors. Methods: Pts with advanced melanoma (AJCC stages IIIC or IV) who were in complete remission for at least 2 y after treatment initiation, were eligible for this ongoing study. Data on health related quality of life (HRQOL), psychosocial outcome and neurocognitive function (NCF) were collected using 5 validated questionnaires, a semi-structured psychiatric examination (SSPE), and computer-based NCF testing. Results: Test results from 17 pts (5 F/12 M), median age 57 y (range 33-86) were analyzed. Median time since start of IPI was 5.5 y (range 2-7). Seven pts (41%) had elevated scores on the Cognitive Failure Questionnaire (CFQ). Nine pts (53%) had elevated scores on the Hospitalization Depression Scale (HADS) indicating moderate anxiety (4 pts), severe anxiety (2 pts), and moderate depression (3 pts). The SSPE revealed that all 10 pts who were professionally active at the time of diagnosis, had to change or stop work due to their illness. Nine pts (53%) reported persisting emotional distress: anxiety, existential problems, survivor guilt, post-traumatic stress symptoms or daily worrying about the disease. Three pts were referred for suicidal ideation in relation with their disease. Four pts (24%) developed hypophysitis and suffered from comorbid depression (1 pt), adjustment disorder (2 pt), or post-traumatic stress disorder related to the symptoms of hypopituitarism (1 pt). Five years after the incidence of hypophysitis, all pts had elevated scores on the Fatigue Severity Scale, the HADS; and 3 pts on the CFQ. All cases of skin toxicity (8 pts), hepatitis (2 pts), colitis (2 pts), sarcoidosis (2 pts), and Guillain-Barre syndrome (1 pt) resolved without long-term impact on HRQOL. Conclusions: A majority of melanoma survivors treated with IPI continues to suffer from emotional distress and cognitive problems impacting their HRQOL. Timely detection and providing adaptive care is imperative.