Novel combination strategies for enhancing efficacy of immune checkpoint inhibitors in the treatment of metastatic solid malignancies

2017 ◽  
Vol 18 (14) ◽  
pp. 1477-1490 ◽  
Author(s):  
Michael J. Flynn ◽  
James M.G. Larkin
2021 ◽  
Vol 28 (5) ◽  
pp. 3227-3239
Author(s):  
Lisa Kinget ◽  
Oliver Bechter ◽  
Kevin Punie ◽  
Philip R. Debruyne ◽  
Hilde Brems ◽  
...  

In recent years, immune checkpoint inhibitors (ICPI) have become widely used for multiple solid malignancies. Reliable predictive biomarkers for selection of patients who would benefit most are lacking. Several tumor types with somatic or germline alterations in genes involved in the DNA damage response (DDR) pathway harbor a higher tumor mutational burden, possibly associated with an increased tumoral neoantigen load. These neoantigens are thought to lead to stronger immune activation and enhanced response to ICPIs. We present a series of seven patients with different malignancies with germline disease-associated variants in DDR genes (BRCA1, BRCA2, CHEK2) responding favorably to ICPIs.


Immunotherapy ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 419-432
Author(s):  
Vincenzo Di Nunno ◽  
Giacomo Nuvola ◽  
Mirta Mosca ◽  
Ilaria Maggio ◽  
Lidia Gatto ◽  
...  

Brain metastases (BMs) represent a negative prognostic factor for patients with solid malignancies. BMs are generally approached with loco-regional treatments and the blood–brain barrier limits the efficacy of some systemic drugs. The aim of this review is to summarize current knowledge about the role of immune checkpoint inhibitors for the management of brain metastases in patients with solid malignancies. We performed a review of available literature. Immune checkpoint inhibitors represent the standard treatment for several advanced solid malignancies. However, with the exception of melanoma their clinical role in other solid malignancies is not completely clear due to the exclusion of patients with BM from approval clinical trials. Immune-checkpoint inhibitors may be an effective treatment of brain metastases of melanoma while their clinical role on brain metastases from other solid malignancies is uncertain.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 66
Author(s):  
Edith Borcoman ◽  
Maud Kamal ◽  
Grégoire Marret ◽  
Celia Dupain ◽  
Zahra Castel-Ajgal ◽  
...  

Immunotherapy has made a breakthrough in medical oncology with the approval of several immune checkpoint inhibitors in clinical routine, improving overall survival of advanced cancer patients with refractory disease. However only a minority of patients experience a durable response with these agents, which has led to the development of combination strategies and novel immunotherapy drugs to further counteract tumor immune escape. Epigenetic regulations can be altered in oncogenesis, favoring tumor progression. The development of epidrugs has allowed targeting successfully these altered epigenetic patterns in lymphoma and leukemia patients. It has been recently shown that epigenetic alterations can also play a key role in tumor immune escape. Epidrugs, like HDAC inhibitors, can prime the anti-tumor immune response, therefore constituting interesting partners to develop combination strategies with immunotherapy agents. In this review, we will discuss epigenetic regulations involved in oncogenesis and immune escape and describe the clinical development of combining HDAC inhibitors with immunotherapies.


2020 ◽  
Vol 21 (5) ◽  
pp. 1658
Author(s):  
Caterina Vivaldi ◽  
Silvia Catanese ◽  
Valentina Massa ◽  
Irene Pecora ◽  
Francesca Salani ◽  
...  

Esophageal cancer remains a challenging disease due to limited treatment options and poor prognosis. In recent years, immune checkpoint inhibitors (ICI) have been proven to be safe and effective in the treatment of highly lethal malignancies, such as non-small cell lung cancer and melanoma. Recent clinical trials also showed promising activity in immune checkpoint inhibitors in pretreated advanced esophageal carcinoma and a potentially significant impact on the outcome of selected patients, independently of histology. Combination studies evaluating immunotherapy and chemotherapy and, in localized disease, radiotherapy are in progress and will hopefully confirm their promises in the near future. However, reliable predictive biomarkers are still lacking. Indeed, at present, the role of programmed cell death ligand 1 expression and other factors (such as microsatellite instability and tumor mutational burden) as predictive biomarkers of benefit to immune checkpoint inhibitors is still controversial. Our aim was to explore the rationale of ICIs in esophageal cancer, review the results already available in multiple settings, and investigate future perspectives with single-agent and combination strategies.


2020 ◽  
Vol 9 (6) ◽  
pp. 1721 ◽  
Author(s):  
Lucia Musacchio ◽  
Serena Maria Boccia ◽  
Giuseppe Caruso ◽  
Giusi Santangelo ◽  
Margherita Fischetti ◽  
...  

Although around 80% of endometrial cancers are diagnosed at early stages and present with a 5-year survival rate exceeding 95%, patients with advanced and recurrent disease show a poor prognosis and low response rates to standard chemotherapy. In the era of targeted therapy, the great advances in the understanding of programmed death-ligand 1 (PD-L1) upregulation in cancer cells, which is responsible for tumor immune escape, have contributed to the increasing interest in immune checkpoint inhibitors as a promising strategy for the treatment of several refractory solid malignancies, including endometrial cancer. Several clinical trials have investigated the efficacy and safety of immune checkpoint inhibitors in endometrial cancer, which already led to the approval of the anti-programmed cell death protein 1 (anti-PD-1) antibody pembrolizumab as a satisfactory alternative for selected patients with unresectable or metastatic disease. As the future of cancer treatment will probably rely on combination therapy strategies, currently, innovative ongoing trials are exploring the potential role of immune checkpoint inhibitors associated with chemotherapy, radiotherapy, and other targeted therapies. Moreover, further research is warranted to discover new specific biomarkers that can accurately predict the response to immunotherapy.


Immunotherapy ◽  
2019 ◽  
Vol 11 (17) ◽  
pp. 1507-1521 ◽  
Author(s):  
Francesco Massari ◽  
Vincenzo Di Nunno ◽  
Veronica Mollica ◽  
Rodolfo Montironi ◽  
Liang Cheng ◽  
...  

Management of metastatic renal cell carcinoma has been enriched by the advent of new therapeutic compounds. The approval of new combination strategies between targeted agents and immune-checkpoint inhibitors as well as the administration of combinations between immune-checkpoint inhibitors has clearly demonstrated significant improvement toward patients’ prognosis and other clinical outcomes. Due to the availability of different treatments, the choice between them may be a difficult issue in our clinical practice. We have summarized current knowledge about available treatments focusing on criteria, which may help clinicians to make decisions.


2017 ◽  
Vol 23 ◽  
pp. 176-177
Author(s):  
Kaitlyn Steffensmeier ◽  
Bahar Cheema ◽  
Ankur Gupta

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