scholarly journals Anti-PD-1, anti-VEGF, and temozolomide therapy in a patient with recurrent glioblastoma: a case report

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095139
Author(s):  
Can Chen ◽  
Wenwei Zuo ◽  
Pan Yang ◽  
Yanling Zhang
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
Vascular Endothelial ◽  
Case Presentation ◽  
Programmed Death ◽  
Endothelial Growth Factor

Background Patients suffering from postoperative recurrent glioblastoma have an extremely unfavorable outcome because there are no proven therapeutic options. The median overall survival for those with relapsed glioblastoma after surgery is only 7.5 months. Case presentation: Between March 2015 and October 2019, a 44-year-old female patient with recurrent glioblastoma was treated by our medical team. After several failed rounds of therapy, the patient was subsequently treated with the anti-programmed death (PD)-1 antibody nivolumab, anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and cytotoxic agent temozolomide. Results The patient showed a sustainable complete response to the regimen. To date, there have been no serious toxic side effects. As of October 2019 (the last follow-up), the patient has been in complete remission for 17 months since recurrence. Conclusion The experience of this complicated case indicates the possible application of immune checkpoint inhibitors, anti-angiogenesis agents, and cytotoxic reagents for recurrent glioblastoma. The administration of this three-agent regimen appears safe and effective. However, further clinical trials are warranted.

scholarly journals Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1223
Author(s):  
Daniel Pink ◽  
Dimosthenis Andreou ◽  
Sebastian Bauer ◽  
Thomas Brodowicz ◽  
Bernd Kasper ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Phase Ii Trial ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Future Studies ◽  
Entire Cohort

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7–15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

scholarly journals A Contemporary Review of Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 919
Author(s):  
Eun-mi Yu ◽  
Laura Linville ◽  
Matthew Rosenthal ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Vascular Endothelial ◽  
Vegf Inhibitors ◽  
Cell Renal Cell Carcinoma ◽  
Improved Outcomes ◽  
Immune Oncology ◽  
Endothelial Growth Factor

The use of checkpoint inhibitors in advanced and metastatic renal cell carcinomas (RCCs) has rapidly evolved over the past several years. While immune-oncology (IO) drug therapy has been successful at resulting in improved responses and survival, combination therapies with immune checkpoint inhibitors and vascular endothelial growth factor (VEGF) inhibitors have further improved outcomes. This article reviews the landmark trials that have led to the approval of IO therapies, including the Checkmate 214 trial and combination IO/VEGF TKI therapies with Checkmate 9ER, CLEAR, and Keynote-426, and it includes a discussion on promising therapies moving in the future.

scholarly journals Emerging and Novel Treatments for Pituitary Tumors

2019 ◽  
Vol 8 (8) ◽  
pp. 1107 ◽  
Author(s):  
Ilie ◽  
Lasolle ◽  
Raverot
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Radionuclide Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Vascular Endothelial ◽  
Peptide Receptor ◽  
Radiological Response ◽  
Endothelial Growth Factor

A subset of pituitary neuroendocrine tumors (PitNETs) have an aggressive behavior, showing resistance to treatment and/or multiple recurrences in spite of the optimal use of standard therapies (surgery, conventional medical treatments, and radiotherapy). To date, for aggressive PitNETs, temozolomide (TMZ) has been the most used therapeutic option, and has resulted in an improvement in the five-year survival rate in responders. However, given the fact that roughly only one third of patients showed a partial or complete radiological response on the first course of TMZ, and even fewer patients responded to a second course of TMZ, other treatment options are urgently needed. Emerging therapies consist predominantly of peptide receptor radionuclide therapy (20 cases), vascular endothelial growth factor receptor-targeted therapy (12 cases), tyrosine kinase inhibitors (10 cases), mammalian target of rapamycin (mTOR) inhibitors (six cases), and more recently, immune checkpoint inhibitors (one case). Here, we present the available clinical cases published in the literature for each of these treatments. The therapies that currently show the most promise (based on the achievement of partial radiological response in a certain number of cases) are immune checkpoint inhibitors, peptide receptor radionuclide therapy, and vascular endothelial growth factor receptor-targeted therapy. In the future, further improvement of these therapies and the development of other novel therapies, their use in personalized medicine, and a better understanding of combination therapies, will hopefully result in better outcomes for patients bearing aggressive PitNETs.

Outcomes of Lynch syndrome (LS) patients treated with immune checkpoint inhibitors (ICI).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1548-1548
Author(s):  
Shahla Bari ◽  
Richard D. Kim ◽  
Xia Wang ◽  
Marco Matejcic ◽  
Jameel Muzaffar
Keyword(s):  
Lynch Syndrome ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
The Mean ◽  
The One

1548 Background: LS is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2 (d-MMR). A minority of LS patients have MMR proficient tumors (p-MMR). ICI therapy has dramatically changed outcome of d-MMR (majority of LS patients. However, data about response to ICI in LS patients, irrespective of their tumor MMR status is scarce. The aim of this study was to evaluate outcomes of ICI therapy in all LS associated Cancer. Methods: This was a retrospective analysis of LS associated cancers treated with one of the 6 ICIs at our center. We also looked at age, sex, microsatellite status, response and survival. Results: Out of 262 LS patients analyzed, 194 had cancer and 22 received ICIs. Among the patients analyzed, the mean age at diagnosis of 1st cancer was 51 yrs. There were 10 females (47%). 10 patients had colorectal (45%), 3 urothelial (14%), 2 renal cell, 2 cholangiocarcinoma and one each of esophageal, ovarian, uterine, glioblastoma multiforme and pancreatic cancer. One patient died from progressive disease after receiving a single dose and was not included in the analysis. 17 patients (80%) received Pembrolizumab, 11 patients were microsatellite unstable (MSI), 3 were microsatellite stable (MSS) while 7 were unknown. 2 patients achieved complete response (CR) (10%), 1 patient had partial response (PR) (5%), 13 had stable disease (62%) while 5 had progressive disease (23%) leading to a disease control rate (DCR) of 76%. Of the 3 known MSS Lynch syndrome patients, 2 did not respond while the 3rd continues to respond at 9 months of therapy. Of the 5 patients who had PD, 2 were MSS, 2 unknown and 1 MSI. Among the 16 patients who responded, 15 of 16 (94%) had sustained response and have not experienced disease progression or relapse. 3 of these patients have been off therapy (1 due to immune related adverse evet) and have had no relapse. One responder progressed after 18 cycles of therapy. The DCR was 71% at 12 months as well as 48 months of follow up. Median progression survival has not been reached. Similarly, median overall survival has not been reached. Conclusions: Our study is the one of the largest reported analysis of LS associated cancer patients treated with ICIs and included LS patients with both MSI and MSS tumors. Though small, our data suggests robust DCR and prolonged responses in Lynch associated MSS tumors treated with ICI. This encouraging response in MSS tumors along with higher response rates in LS associated cancers as compared to non-LS MSI tumors, suggests that there may be additional drivers of response to ICI in LS patients leading to superior responses.

scholarly journals Cardio-Oncology: mechanisms of cardiovascular toxicity

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 113 ◽  
Author(s):  
Timothy M. Markman ◽  
Maurie Markman
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Chemotherapeutic Agents ◽  
Vascular Endothelial ◽  
Cardiovascular Toxicity ◽  
Management Of Complications ◽  
Wide Range ◽  
Endothelial Growth Factor

The therapeutic options available to treat a wide range of malignancies are rapidly increasing. At the same time, the population being treated is aging with more cardiovascular risk factors, comorbid conditions, and associated poor cardiac reserve. Both traditional chemotherapeutic agents (for example, anthracyclines) and newer therapies (for example, targeted tyrosine kinase inhibitors and immune checkpoint inhibitors) have demonstrated profound cardiovascular toxicities. It is important to understand the mechanisms of these toxicities to establish strategies for the prevention and management of complications—arrhythmias, heart failure, and even death. In the first of this two-part review series, we focus on what is known and hypothesized about the mechanisms of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

scholarly journals Cardio-oncology: management of cardiovascular toxicity

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 120
Author(s):  
Timothy M. Markman ◽  
Maurie Markman
Keyword(s):  
Heart Failure ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Management Strategies ◽  
Chemotherapeutic Agents ◽  
Vascular Endothelial ◽  
Cardiovascular Toxicity ◽  
Careful Monitoring ◽  
Vascular Toxicity ◽  
Endothelial Growth Factor

Traditional chemotherapeutic agents and newer targeted therapies for cancer have the potential to cause cardiovascular toxicities. These toxicities can result in arrhythmias, heart failure, vascular toxicity, and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and management strategies to employ when these toxicities occur. While anti-neoplastic therapy occasionally must be discontinued in this setting, it can often be maintained with caution and careful monitoring. In the second of this two-part review series, we focus on the management of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

scholarly journals Update on immunotherapy for renal cancer

Medwave ◽  
2021 ◽  
Vol 21 (05) ◽  
pp. e8202-e8202
Author(s):  
Rodrigo Canales Rojas
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Renal Cell Carcinoma ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

In the last decade, the development of immune checkpoint inhibitors have revolutionized the treatment of patients with advanced renal cell carcinoma, with the potential for dramatic changes in the therapeutic landscape. Nivolumab, a monoclonal antibody inhibitor of transmem-brane programmed cell death protein 1 (PD-1), was approved as monotherapy in 2015 for advanced renal cell carcinoma in patients previously treated with an agent targeting vascular endothelial growth factor. In April 2018, the combination of nivolumab and ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 inhibitor, was approved for patients with previously untreated intermediate- and poor-risk advanced renal cell carcinoma. Then, in 2019, combination therapies consisting of pembrolizumab (anti-PD-1) or avelumab (anti-PD-1 ligand, PD-L1) with axitinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) were also approved for use in all risk groups. This review pre-sents a brief historical review of the association between immunology and oncology; describes essential aspects of the mechanism of action of immune checkpoint inhibitors; discusses the current evidence regarding the clinical use of different immunotherapy regimens for the treatment of patients with renal cell carcinoma, both clear cell and other histological types; and provides general information on their adverse effects. The role of appropriate patient selection is analyzed to allow individualization of therapy and improve the already promising results. Finally, per-spectives on the future use of immune checkpoint inhibitors to treat renal cancer are discussed.

scholarly journals Ipilimumab and Stereotactic Radiosurgery with CyberKnife® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1857
Author(s):  
Valentina Borzillo ◽  
Rossella Di Franco ◽  
Diana Giannarelli ◽  
Fabrizio Cammarota ◽  
Esmeralda Scipilliti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Local Control ◽  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Melanoma Brain Metastases ◽  
One Year ◽  
The Impact

The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.

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