Purpose: Glioblastoma represents the most common primary brain tumor. Although antiangiogenics are used in the recurrent setting, they do not prolong survival. Glioblastoma is known to upregulate fatty acid synthase (FASN) to facilitate lipid biosynthesis. TVB-2640, a FASN inhibitor, impairs this activity. Patients and Methods: We conducted a prospective, single-center, open-label, unblinded, phase II study of TVB-2640 plus bevacizumab in patients with recurrent high-grade astrocytoma. Patients were randomly assigned to TVB-2640 (100 mg/m2 oral daily) plus bevacizumab (10 mg/kg i.v., D1 and D15) or bevacizumab monotherapy for cycle 1 only (28 days) for biomarker analysis. Thereafter, all patients received TVB-2640 plus bevacizumab until treatment-related toxicity or progressive disease (PD). The primary endpoint was progression-free survival (PFS). Results: A total of 25 patients were enrolled. The most frequently reported adverse events (AE) were palmar–plantar erythrodysesthesia, hypertension, mucositis, dry eye, fatigue, and skin infection. Most were grade 1 or 2 in intensity. The overall response rate (ORR) for TVB-2640 plus bevacizumab was 56% (complete response, 17%; partial response, 39%). PFS6 for TVB-2640 plus bevacizumab was 31.4%. This represented a statistically significant improvement in PFS6 over historical bevacizumab monotherapy (BELOB 16%; P = 0.008) and met the primary study endpoint. The observed OS6 was 68%, with survival not reaching significance by log-rank test (P = 0.56). Conclusions: In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab. The favorable safety profile and response signals support the initiation of a larger multicenter trial of TVB-2640 plus bevacizumab in astrocytoma.

Background: Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. The standard-of-care immunochemotherapy, R-CHOP, cures only about 60% of DLBCL patients. Improving this cure rate will likely require the effective translation of basic biology knowledge into clinical activities. We previously identified the cyclic-AMP/phosphodiesterase 4 (PDE4) axis as an important modulator of lymphomagenic processes. We also showed that the FDA-approved PDE4 inhibitor roflumilast can suppress B-cell receptor (BCR) signals, phosphoinositide 3-kinase (PI3K) activity and angiogenesis. These data suggested that combining roflumilast with R-CHOP may be beneficial in DLBCL. Methods: We conducted a single-center, single-arm, open-label, phase 1 study of roflumilast in combination with the standard of care, R-CHOP (Ro+R-CHOP), in pathologically proven, treatment-naïve, high-risk DLBCL patients. Results: Ro+R-CHOP was safe, and at a median follow-up time of 44 months, 70% of patients were alive and disease free (median OS not reached, PFS 44% (95% CI, 21–92). In this pilot series, we found that the addition of roflumilast suppressed PI3K activity in peripheral blood mononuclear cells, and VEGF-A secretion in the urine. We also encountered preliminary evidence to suggest that the Ro+R-CHOP combination may be particularly beneficial to patients diagnosed with high-risk genetic subtypes of DLBCL, namely MCD and A53. Conclusions: These initial findings suggest that roflumilast may be an alternative agent able to inhibit BCR/PI3K activity and angiogenesis in DLBCL, and that the testing of Ro+R-CHOP in a larger series of genetically characterized tumors is warranted. This study was registered at ClinicalTrials.gov, number NCT03458546.

Purpose:Glioblastoma represents the most common primary brain tumor. Although antiangiogenics are used in the recurrent setting, they do not prolong survival. Glioblastoma is known to upregulate fatty acid synthase (FASN) to facilitate lipid biosynthesis. TVB-2640, a FASN inhibitor, impairs this activity.Patients and Methods:We conducted a prospective, single-center, open-label, unblinded, phase II study of TVB-2640 plus bevacizumab in patients with recurrent high-grade astrocytoma. Patients were randomly assigned to TVB-2640 (100 mg/m2 oral daily) plus bevacizumab (10 mg/kg i.v., D1 and D15) or bevacizumab monotherapy for cycle 1 only (28 days) for biomarker analysis. Thereafter, all patients received TVB-2640 plus bevacizumab until treatment-related toxicity or progressive disease (PD). The primary endpoint was progression-free survival (PFS).Results:A total of 25 patients were enrolled. The most frequently reported adverse events (AE) were palmar–plantar erythrodysesthesia, hypertension, mucositis, dry eye, fatigue, and skin infection. Most were grade 1 or 2 in intensity. The overall response rate (ORR) for TVB-2640 plus bevacizumab was 56% (complete response, 17%; partial response, 39%). PFS6 for TVB-2640 plus bevacizumab was 31.4%. This represented a statistically significant improvement in PFS6 over historical bevacizumab monotherapy (BELOB 16%; P = 0.008) and met the primary study endpoint. The observed OS6 was 68%, with survival not reaching significance by log-rank test (P = 0.56).Conclusions:In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab. The favorable safety profile and response signals support the initiation of a larger multicenter trial of TVB-2640 plus bevacizumab in astrocytoma.

Purpose: Avanzando Caminos (Leading Pathways): The Hispanic/Latino Cancer Survivorship Cohort Study aims to examine the influence of sociocultural, medical, stress, psychosocial, lifestyle, behavioral, and biological factors on symptom burden, health-related quality of life, and clinical outcomes among Hispanics/Latinos who have been previously treated for cancer. Methods: Avanzando Caminos is a prospective, cohort-based study of 3,000 Hispanics/Latinos who completed primary cancer treatment within the past five years that is representative of the general Hispanic/Latino population in the U.S. Participants will complete self-report measures at baseline (T1), 6 months (T2), 1 year (T3), 2 years (T4), 3 years (T5), 4 years (T6), and 5 years (T7). Blood draws to assess leukocyte gene expression, cardiometabolic markers, and genetic admixture will be collected at baseline (T1), 1 year (T3), 3 years (T5), and 5 years (T7). Medical and cancer characteristics and clinical outcomes will be extracted from the electronic medical record and/or state cancer registry at each time point. Data analysis will include general latent variable modeling and latent growth modeling. Conclusions: Avanzando Caminos will fill critical gaps in knowledge to guide future secondary and tertiary prevention efforts to mitigate cancer disparities and optimize health-related quality of life among Hispanic/Latino cancer survivors.

E14553 Background: Primary CNS lymphoma (PCNSL) is a rare malignancy, comprising only 2% of primary CNS tumors in the United States.While it’s incidence has decreased in the immunocompromised population (HIV positive) secondary to widespread access of effective anti-retroviral therapy, it is suspected that the rates are increasing among immunocompetent people aged 65+ years at a rate of approximately 1.7% per year. Data from the Surveillance, Epidemiology, and End Results (SEER) looking into survival and incidence patterns in PCNSL have a majority of non-Hispanic (NH) white population with lesser proportion of other ethnicities. Understanding racial and ethnic disparities on outcomes and patterns of care are crucial given the rapid growth of the Hispanic (HI) population in the US. Therefore, our study aims to compare survival outcomes and contributing factors in HI vs NH with PCNSL, who were treated at the only NCI designated Cancer Center in South Texas. Methods: This is a retrospective study, where we identified patients who were diagnosed and treated for PCNSL at UT Health San Antonio, between January 2008 and December 2018. The patient characteristics, treatment patterns, and clinical outcomes were listed as descriptive statistics. Results: From 2008-2018, a total of 29 patients with PCNSL were included. Among those, 62% were HI(Hispanic) and the remaining 38% were NH(Non-Hispanic). The median age at diagnosis was 61 years (58 years in HI and 70 years in NH). 55% were below 65 years and 45% were older than 65 years. Everyone received chemotherapy (89% received R-MPV (DeAngelis protocol) and 9% received other high dose methotrexate containing regimens). However, in terms of receiving Whole Brain Radiation Therapy (WBRT), the patients in the younger group were more likely to receive it than were those in the elderly group (68% versus 23% respectively). Overall Survival (OS) rate at 3 years was 41 % in HI and 33 % in NH (p = 0.08) and at 5 years was 41 % in HI and 25 % in NH (p = 0.03). Conclusions: While there is increasing data on higher incidence of non-HIV PCNSL in elderly population > 65 years, HI in our study population had a significantly lower median age at diagnosis with better survival and outcomes. Further studies on a larger patient population may help to describe the differences in incidence, tumor biology, genetics and outcomes in HI population.