Off label targeted therapy use in adolescents and young adults with sarcoma.

e21504 Background: Outcomes for patients with metastatic or recurrent sarcomas remains dismal with < 20% overall survival. Due to the rarity of sarcomas, the development, testing, and approval of new therapies takes years. Most early phase clinical trials are restricted to adults leaving young patients with limited options. Little is known about the prevalence and clinical characteristics of patients receiving off-label targeted therapy (OLTT). In this multi-institutional retrospective review we evaluated OLTT use in this population. Methods: Patients with recurrent sarcoma diagnosed between the years of 2008 – 2016 were identified at six institutions. Charts were reviewed for OLTT use and additional clinical characteristics. ANOVA [Analysis of Variance] and Kruskal Wallis Rank sum tests were used for normally and non-normally distributed continuous data. Categorical data was analyzed using chi-squared tests or fisher exact tests. Results: The prevalence of OLTT use was 29% for the patients included in our analysis. Of the 99 cases, the mean age for OLTT was 18 years, ranging 3 – 34 years. Nearly half had recurrent tumor in multiple sites at the time of OLTT use, and 64% did not undergo resection prior to OLTT. Lack of clinical trial availability was the most common reason for OLTT use (31% of cases). The most common OLTT drug class used were tyrosine kinase inhibitors. Progression in 81% of cases was the primary reason for stopping OLTT and toxicity limited use in 12% of cases. One case had a complete response, 5 cases had a partial response and 4 cases had stable disease per RECIST. Conclusions: OLTT use is exceedingly prevalent in patients with recurrent sarcoma. Clinical trials for children and adolescents with recurrent sarcoma will identify optimal agents to improve outcomes in this understudied population.

Download Full-text

Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus

Blood ◽

10.1182/blood-2014-03-565135 ◽

2014 ◽

Vol 124 (9) ◽

pp. 1404-1411 ◽

Cited By ~ 85

Author(s):

Meletios A. Dimopoulos ◽

Efstathios Kastritis ◽

Roger G. Owen ◽

Robert A. Kyle ◽

Ola Landgren ◽

...

Keyword(s):

Clinical Trials ◽

Kinase Inhibitors ◽

Treatment Options ◽

Autologous Transplantation ◽

Mammalian Target Of Rapamycin ◽

Proteasome Inhibitors ◽

Young Patients ◽

Treatment Recommendations ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia

Abstract Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.

Download Full-text

Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board

JCO Precision Oncology ◽

10.1200/po.16.00046 ◽

2017 ◽

pp. 1-19 ◽

Cited By ~ 12

Author(s):

W. Brian Dalton ◽

Patrick M. Forde ◽

Hyunseok Kang ◽

Roisin M. Connolly ◽

Vered Stearns ◽

...

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Targeted Therapies ◽

Progression Free Survival ◽

Molecular Profiling ◽

Tumor Board ◽

Free Survival ◽

Off Label ◽

Tumor Boards ◽

Molecular Tumor Board

Purpose Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice. Methods A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration–approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing. Results One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months ( 95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43% (95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports. Conclusion The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.

Download Full-text

Analysis of real-world data (RWD) on treatment (tx) sequencing in patients with advanced non-small cell lung cancer (aNSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e20642 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e20642-e20642

Author(s):

Meng Ma ◽

Xiang Zhou ◽

Howard Goldsweig ◽

Nicholas Hahner ◽

Dianwei Han ◽

...

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Rank Test ◽

Real World Data ◽

Therapeutic Modalities ◽

Platinum Based Chemotherapy ◽

Line Of Therapy ◽

Line Setting

e20642 Background: While optimal sequencing of systemic therapy in aNSCLC is critical to achieve maximal clinical benefit, it is practically challenging to study tx sequencing through clinical trials. RWD allow retrospective, observational studies to examine tx patterns and associated clinical outcomes. Methods: 1,609 aNSCLC patients who received systemic therapies at Mount Sinai hospitals were analyzed for the number of line of therapy (LOT), therapeutic modalities (chemotherapy, targeted therapy and immunotherapy), and the sequence in which treatments were given when LOT > 1. Time to tx discontinuation (TTD) was used as a surrogate clinical endpoint for outcomes. Results: 578 of the 1,609 (36%) patients received more than one LOT. 356 (22%) received tyrosine kinase inhibitors (TKIs), and 297 (16%) received immune checkpoint inhibitors (CPIs). Kaplan-Meier analysis revealed that among 297 patients who received CPIs, median TTD was longer in the 1st line setting (295 days, 95% CI 169 to 523; n=132) than when LOT > 1 (169 days, 95% CI 113 to 269; n=165), although the difference was not statistically significant (P=0.092, log-rank test). No difference of TTD on TKIs was observed between LOT = 1 and LOT > 1 (P=0.51). With respect to tx sequencing, when patients (n=94) received TKIs as the 1st LOT, 60%, 35%, and 5% of them received another TKI, chemotherapy, or a CPI-containing regimen, respectively, as the 2nd LOT. Among patients (n=370) who progressed on 1st line platinum-based chemotherapy, 52%, 32%, and 16% received another chemo regimen, a CPI-containing regimen, or a targeted therapy, respectively, as the 2nd LOT; these percentages shifted significantly toward more CPIs (24%, 66%, 10% for chemo, CPI, targeted, respectively) when only 2016-2018 data were examined. In the 2nd line setting after platinum therapy, TTD was significantly longer in the CPI group (332 days, 95% CI 169-484) compared to the chemo group (88 days, 95% CI 65-100; P<0.0001), consistent with results from pivotal clinical trials. Conclusions: As the tx algorithm of aNSCLC has been evolving rapidly, we observed diverse tx patterns in RWD. Various tx sequences may impact patient outcomes, and therefore warrant further investigation.

Download Full-text

Efficacy and Safety of Histone Deacetylase Inhibitors in Multiple Myeloma - a Systematic Review of Early Phase Clinical Trials

Blood ◽

10.1182/blood-2018-99-114019 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5629-5629

Author(s):

Sharoon Samuel ◽

Muhammad Junaid Tariq ◽

Muhammad Usman ◽

Amna Khalid ◽

Muhammad Asad Fraz ◽

...

Keyword(s):

Systematic Review ◽

Multiple Myeloma ◽

Clinical Trials ◽

Adverse Events ◽

Phase I ◽

Hdac Inhibitors ◽

Complete Response ◽

Number Of Patients ◽

Grade 3 ◽

Early Phase Clinical Trials

Abstract Introduction Recent studies in novel therapies have created opportunities for new treatment regimens to be used in the management of multiple myeloma. Histone deacetylase (HDAC) inhibitors lead to epigenetic manipulation of multiple myeloma (MM) cells by reducing resistance to pro-apoptotic signals. Panobinostat is an FDA approved HDAC inhibitor for multiple myeloma. The aim of this article is to study the safety, efficacy and dose limiting toxicities of HDAC inhibitors in the early phase clinical trials in multiple myeloma. Methods We performed a comprehensive literature search for phase I & I/II trials of HDAC inhibitors during last ten years using following databases: PubMed, Embase, AdisInsight, and Clinicaltrials.gov. Studies involving HDAC inhibitors in multiple myeloma other than panobinostat irrespective of the age, sex or specific eligibility criteria were included. Results Out of 2537 studies, we included 25 trials (23 phase I, 2 phase I/II) of HDAC inhibitors in this systematic review having a total of 518 patients. Of these, 471(90.9%) patients were evaluable for response. Vorinostat (Vor) is the most studied drug used in 13 trials (n=281). Two trials had Vor-only regimen and the remaining 11 had combination regimens mostly with lenalidomide and bortezomib. Vor, in combination with lenalidomide (R), bortezomib (V) and dexamethasone (d) has showed 100% overall response rate (ORR) in 30 newly diagnosed multiple myeloma (NDMM) patients, (Kaufmann et al., 2016), fifty two percent patients achieved very good partial response (VGPR) and 28% patients showed complete response (CR). Another study using Vor + R regimen after autologous stem cell transplant in 16 NDMM patients showed VGPR in 7, stringent complete response (sCR) in 4, partial response (PR) in 2 and CR in 3 patients (Sborov et al.). Grade 3 neutropenia was seen in 1 patient in this study. Richter et al, 2011 showed an ORR of 24% in 29 relapsed refractory multiple myeloma (RRMM) patients with Vor only regimen. Another study (Kaufmann et al., 2012) with Vor only regimen used in 10 RRMM patients showed stable disease (SD) in 9 and minimal response (MR) in 1 patient. ORR of 65% was achieved in 31 RRMM patients receiving Vor in combination with doxorubicin & bortezomib (Vorhees et al, 2017). Thrombocytopenia & neutropenia were reported in 94% and 59% patients respectively. Ricolinostat in combination with Rd and Vd achieved an ORR of 55% and 29% respectively in two studies with 38 and 57 evaluable patients (NCT01583283, NCT01323751). Another ricolinostat regimen with pomalidomide & dexamethasone achieved ≥PR in 6/11 RRMM patients (Madan et al., 2016). Table 1 illustrates the efficacy, number of patients and regimens used in all the studies in this systematic review. Quisinostat in a 2017 study by Moreau P et al. (NCT01464112) showed an ORR of 88% in a combination regimen with Vd in RRMM patients (N=18). Drug related adverse events were seen in 13 patients, thrombocytopenia being most common in 11 patients, 2 patients had grade 3 cardiac disorders and 1 patient had a cardiac arrest. Romidepsin in a phase I/II study (Harrison et al., 2011) combined with Vd was used in 25 RRMM patients. ORR was 60% with VGPR n=7, CR n=2, PR n=6, SD n=5 and PD n=1. Grade ≥3 thrombocytopenia in 16, neutropenia in 9 and peripheral neuropathy in 2 patients was seen. Popat et al used combination of two HDAC inhibitors CHR 3996 and tosedostat in 20 RRMM patients. ORR was 10% and SD was seen in 30% patients. Grade 3/4 toxicities seen were thrombocytopenia (n=12), leukopenia (n=6) and diarrhea (n=5). A phase I study on AR-42 drug in 17 RRMM patients (Sborov et al., 2017) showed SD in 10, PD in 4, MR in 3 patients with progression free survival (PFS) of 8.2 months. Thrombocytopenia, neutropenia and lymphopenia were seen in 11, 10 and 6 patients respectively. A detail of all grade 3 and higher adverse events along with dose limiting toxicity is given in table 2. Three trials (NCT02576496, NCT01947140, NCT03051841) of Edo-S101, romidepsin and CKD-581 are currently recruiting with 84, 93 and 18 planned number of patients. Conclusion Regimens containing vorinostat have shown an ORR up to 100% in NDMM patients. HDAC inhibitors have also shown promising efficacy up to 88% ORR in RRMM population. Majority of the patients developed cytopenias as hematological adverse events. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Clinical utility of targeted next generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making

Neuro-Oncology ◽

10.1093/neuonc/noab282 ◽

2021 ◽

Author(s):

Mary Jane Lim-Fat ◽

Gilbert C Youssef ◽

Mehdi Touat ◽

J Bryan Iorgulescu ◽

Sydney Whorral ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Targeted Therapy ◽

Clinical Utility ◽

Clinical Care ◽

Clinical Trial Design ◽

Off Label ◽

Survival Difference ◽

Clinical Trial Enrollment ◽

Clinical Records

Abstract BACKGROUND Targeted gene NGS testing is available through many academic institutions and commercial entities and is increasingly incorporated in practice guidelines for glioblastoma (GBM). This single-center retrospective study aimed to evaluate the clinical utility of incorporating NGS results in the management of GBM patients at a clinical trials-focused academic center. METHODS We identified 1,011 consecutive adult patients with pathologically confirmed GBM (IDHwt or IDHmut) who had somatic tumor sequencing (Oncopanel, ~500 cancer gene panel) at DFCI from 2013-2019. Clinical records of all IDHwt GBM patients were reviewed to capture clinical trial enrollment and off-label targeted therapy use based on NGS results. RESULTS Of the 557 IDHwt GBM patients with sequencing, 182 entered clinical trials at diagnosis (32.7%) and 213 (38.2%) entered after recurrence. Sequencing results for 130 patients (23.3%) were utilized for clinical trial enrollment for either targeted therapy indications (6.9 % upfront and 27.7% at recurrent clinical trials and 3.1% for off-label targeted therapy) or exploratory studies (55.4% upfront and 6.9% recurrent clinical trials). Median overall survival was 20.1 months with no survival difference seen between patients enrolled in clinical trials compared to those who were not, in a post hoc analysis. CONCLUSIONS While NGS testing has become essential for improved molecular diagnostics, our study illustrates that targeted gene panels remain underutilized for selecting therapy in GBM-IDHwt. Targeted therapy and clinical trial design remain to be improved to help leverage the potential of NGS in clinical care.

Download Full-text

P166 Multimorbidity in SLE, a barrier to clinical trial eligibility: results from the BILAG-BR

Rheumatology ◽

10.1093/rheumatology/keab247.162 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Sarah Dyball ◽

Sophie Collinson ◽

Emily Sutton ◽

Eoghan McCarthy ◽

Ben Parker ◽

...

Keyword(s):

Clinical Trials ◽

Real World ◽

Phase Iii ◽

Research Support ◽

Exclusion Criteria ◽

Eligibility Criteria ◽

Chi Squared ◽

The Mean ◽

Double Blinded ◽

Age And Sex

Abstract Background/Aims Stringent inclusion and exclusion criteria are employed in SLE clinical trials. Organ dysfunction and co-morbidities are common exclusion criteria which may affect how representative trials are of real-world SLE populations. We aimed to apply published trial eligibility criteria to patients with SLE in a large national register. Methods A literature review of all major published double-blinded randomised phase III trials in non-renal SLE was performed. Common inclusion and exclusion criteria were applied to all patients recruited to the BILAG-Biologics Register (BILAG-BR), a large UK-wide register of SLE patients. Data on comorbidities for all patients registered was collected. The mean (SD) number of co-morbidities was calculated. Patients were then classified as being eligible or ineligible. Groups were compared initially using a chi-squared or Wilcoxon rank-sum test and logistic regression model was used to test the age and sex adjusted association between trial eligibility and comorbidities. Results Common inclusion and exclusion criteria were identified from 12 published trials. When applied to the 837 patients recruited to BILAG-BR, 562 (67%) patients would not be eligible for inclusion in these trials. Ineligible patients had a shorter disease duration (2.9 vs. 5.1 years, p < 0.01), but were similar in age (P = 1.0), sex (P = 0.7) and ethnicity (p = 0.5) to those who were eligible. Of eligible patients, 128 (53%) had 1 or more comorbidities compared with 340 (60%) who were ineligible (p = 0.05). The mean (SD) number of comorbidities was 0.9 (1.2) vs 1.2 (1.3) for eligible and ineligible patients respectively. After adjusting for age and sex, inclusion in clinical trials was associated with fewer comorbidities (OR 0.81, 95% CI 0.70, 0.94, p < 0.01). Conclusion Patients with multi-morbidity are more likely to be ineligible for SLE clinical trials. Evidence from real world studies and registers are therefore needed to fully understand the safety and effectiveness of new therapies. Our data also underscores the need to develop more pragmatic eligibility criteria for clinical trials. Disclosure S. Dyball: None. S. Collinson: None. E. Sutton: None. E. McCarthy: None. B. Parker: Consultancies; GSK, AstraZenica, UCB, Abbvie, Pfizer, BMS, Celltrion. Grants/research support; GSK, Sanofi Genzyme. I. Bruce: Consultancies; GSK, Medimmune, AstraZenica, Eli Lilly, Merck Serono, UCB, ILTOO. Member of speakers’ bureau; AstraZeneca, Medimmune, GSK, UCB. Grants/research support; GSK, Genzyme Sanofi, UCB.

Download Full-text

COVID-19 infection with asymptomatic or mild disease severity in young patients: Clinical course and association between prevalence of pneumonia and viral load

PLoS ONE ◽

10.1371/journal.pone.0250358 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0250358

Author(s):

Cherry Kim ◽

Wooil Kim ◽

Ji Hoon Jeon ◽

Hyeri Seok ◽

Sun Bean Kim ◽

...

Keyword(s):

Viral Load ◽

Retrospective Study ◽

Disease Severity ◽

Clinical Characteristics ◽

Clinical Course ◽

Young Patients ◽

Viral Loads ◽

Mild Disease ◽

Recovery Times ◽

The Mean

Few studies have focused on clinical courses or viral loads in young asymptomatic or mild patients with COVID-19 infection. We sought to better understand the clinical course and association between viral load and prevalence of pneumonia in young COVID-19 patients with asymptomatic or mild disease severity. In this retrospective study, 106 COVID-19 young patients with asymptomatic or mild disease severity were analyzed for clinical characteristics, clinical course, prevalence of radiologically proven pneumonia and viral load. The cut-off value of viral load for presence of pneumonia was also investigated. The mean age was 28.0±9.3 years. Eleven patients (10.4%) experienced viral remission within one week of diagnosis, but one (0.9%) transferred to the hospital due to aggravation of pneumonia. Patients with pneumonia had significantly higher viral load than those without, and the cut-off value of the Ct value for presence of pneumonia were 31.38. The patients with pneumonia had significantly slower recovery times than those without. Diarrhea was significantly more common in patients with pneumonia than patients without pneumonia. In conclusion, most young asymptomatic and mildly symptomatic patients showed stable clinical course. There were significant differences in viral load and recovery times between patients with and without pneumonia.

Download Full-text

Toxoplasmosis Encephalitis: A Cross-Sectional Analysis at a U.S. Safety-Net Hospital in the Late cART Era

Journal of the International Association of Providers of AIDS Care (JIAPAC) ◽

10.1177/23259582211043863 ◽

2021 ◽

Vol 20 ◽

pp. 232595822110438

Author(s):

Abby Lau ◽

Mamta Khandelwal Jain ◽

Jeremy Yan-Shun Chow ◽

Ellen Kitchell ◽

Susana Lazarte ◽

...

Keyword(s):

Clinical Characteristics ◽

Complete Response ◽

Safety Net ◽

Clinical Severity ◽

People Living With Hiv ◽

Coordinated Care ◽

Cross Sectional ◽

Safety Net Hospital ◽

Chi Squared ◽

New Diagnosis

Despite decreasing incidence of toxoplasmosis encephalitis(TE) among people living with HIV(PLWH) in the late antiretroviral era, U.S. safety-net hospitals still see significant numbers of admissions for TE. Little is known about this population, their healthcare utilization and long-term outcomes. We conducted an 8-year retrospective review of PLWH with TE at a safety-net hospital. Demographics, clinical characteristics, treatments, readmissions, and outcomes were collected. We used chi-squared test to evaluate 6-month all-cause readmission and demographic/clinical characteristics. Of 38 patients identified, 79% and 40% had a new diagnosis of TE and HIV respectively. 59% had 6-month all-cause readmission. Social factors were associated with readmission (uninsured (p = 0.036), Spanish as primary language (p = 0.017), non-adherence (p = 0.030)) and not markers of clinical severity (ICU admission, steroid-use, concomitant infections, therapeutic adverse events). Despite high readmission rates, at follow-up, 60% had a complete response, 30% had a partial response. Improving TE outcomes requires focus on culturally competent, coordinated care.

Download Full-text

The Landscape of Novel Therapeutics and Challenges in Glioblastoma Multiforme: Contemporary State and Future Directions

Pharmaceuticals ◽

10.3390/ph13110389 ◽

2020 ◽

Vol 13 (11) ◽

pp. 389 ◽

Cited By ~ 1

Author(s):

Karam Khaddour ◽

Tanner Johanns ◽

George Ansstas

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Glioblastoma Multiforme ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Tumor Biology ◽

Adoptive Cell Transfer ◽

High Morbidity ◽

Future Directions ◽

Treatment Approaches

Background: Glioblastoma multiforme is a malignant intracranial neoplasm that constitutes a therapeutic challenge because of the associated high morbidity and mortality given the lack of effective approved medication and aggressive nature of the tumor. However, there has been extensive research recently to address the reasons implicated in the resistant nature of the tumor to pharmaceutical compounds, which have resulted in several clinical trials investigating promising treatment approaches. Methods: We reviewed literature published since 2010 from PUBMED and several annual meeting abstracts through 15 September 2020. Selected articles included those relevant to topics of glioblastoma tumor biology, original basic research, clinical trials, seminal reviews, and meta-analyses. We provide a discussion based on the collected evidence regarding the challenging factors encountered during treatment, and we highlighted the relevant trials of novel therapies including immunotherapy and targeted medication. Results: Selected literature revealed four main factors implicated in the low efficacy encountered with investigational treatments which included: (1) blood-brain barrier; (2) immunosuppressive microenvironment; (3) genetic heterogeneity; (4) external factors related to previous systemic treatment that can modulate tumor microenvironment. Investigational therapies discussed in this review were classified as immunotherapy and targeted therapy. Immunotherapy included: (1) immune checkpoint inhibitors; (2) adoptive cell transfer therapy; (3) therapeutic vaccines; (4) oncolytic virus therapy. Targeted therapy included tyrosine kinase inhibitors and other receptor inhibitors. Finally, we provide our perspective on future directions in treatment of glioblastoma. Conclusion: Despite the limited success in development of effective therapeutics in glioblastoma, many treatment approaches hold potential promise including immunotherapy and novel combinational drugs. Addressing the molecular landscape and resistant immunosuppressive nature of glioblastoma are imperative in further development of effective treatments.

Download Full-text