scholarly journals Development of EGFR TKIs and Options to Manage Resistance of Third-Generation EGFR TKI Osimertinib: Conventional Ways and Immune Checkpoint Inhibitors

2020 ◽  
Vol 10 ◽  
Author(s):  
Leilei Wu ◽  
Linping Ke ◽  
Zhenshan Zhang ◽  
Jinming Yu ◽  
Xue Meng
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Resistance Mutation ◽  
Growth Factor Receptor ◽  
Third Generation ◽  
First Line ◽  
Egfr Tkis

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have been first-line therapy in the treatment of non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations. Progression inevitably happens after 10–14 months of first- or second-generation EGFR TKIs treatment for acquired resistance. Owing to the successful identification of EGFR T790M, third-generation EGFR TKIs such as osimertinib were developed to target such resistance mutation. Nowadays, osimertinib has shown its efficacy both in first-line and second-line after resistance to previous generations of TKI treatment of EGFR-mutant NSCLC. However, drug resistance also emerges on third-generation EGFR TKIs. Multiple mechanisms of acquired resistance have been identified, and some novel strategies were reported to overcome third-generation TKI resistance. Immune checkpoint inhibitors (ICIs) have dramatically changed the prognosis of selected patients. For patients with EGFR-addicted metastatic NSCLC, ICIs have also revealed a potential role. In this review, we will take stock of mechanisms of acquired resistance to third-generation TKIs and discuss current challenges and future perspectives in clinical practice.

scholarly journals The Journey of an EGFR-Mutant Lung Adenocarcinoma through Erlotinib, Osimertinib and ABCP Immunotherapy Regimens: Sensitivity and Resistance

2019 ◽  
Vol 12 (3) ◽  
pp. 765-776 ◽  
Author(s):  
Albina Kibirova ◽  
Malcolm D. Mattes ◽  
Matthew Smolkin ◽  
Patrick C. Ma
Keyword(s):  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Tumor Response ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Mutant ◽  
Egfr Tkis ◽  
Guided Therapy

Patients with epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) have several EGFR targeting tyrosine kinase inhibitors (TKIs) available in frontline management. However, the disease will inevitably progress over time due to acquired resistance. Longitudinal tumor profiling for genomics guided therapy is indicated upon disease progression. It is a common scenario yet, when after failure of EGFR-TKIs, potentially actionable genomic alterations are lacking. Management of such patient is challenging with very limited options available. Combination of chemotherapy, anti-vascular/anti-angiogenic and immune-checkpoint inhibitors may become a salvage option for such patients. Here we describe a case of TKI refractory EGFR-mutant NSCLC successfully treated with carboplatin, paclitaxel, atezolizumab and bevacizumab combination with remarkable prompt tumor response.

scholarly journals Emerging role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 698 ◽  
Author(s):  
Longo ◽  
Brunetti ◽  
Gnoni ◽  
Licchetta ◽  
Delcuratolo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Single Agent ◽  
First Line ◽  
Dismal Prognosis ◽  
Programmed Death

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70–80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches.

scholarly journals Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2019 ◽  
Author(s):  
Vito Longo ◽  
Oronzo Brunetti ◽  
Antonio Gnoni ◽  
Antonella Licchetta ◽  
Sabina Del Curatolo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Single Agent ◽  
Locoregional Therapy ◽  
First Line ◽  
Dismal Prognosis

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib has been the standard of care for almost a decade until 2018 when FDA approved an alternative first-line agent namely lenvatinib. Whereas FOLFOX4 results an alternative first-line treatment for the chinese clinical oncology guidelines. In addition to cabozantinib, regorafenib, and ramucirumab, two therapeutics against the PD-L1/PD1 axis have been recently approved for subsequent-line therapy, as nivolumab and pembrolizumab. However, similar to other solid tumors, the response rate of single-agent targeting PD-L1/PD1 axis is low. Therefore a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors, the addition of immune checkpoint inhibitors after resection or during locoregional therapy, immune checkpoint inhibitors in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with an attent evaluation of new ICIs based combinatory approaches.

scholarly journals Clinical Potential of Kinase Inhibitors in Combination with Immune Checkpoint Inhibitors for the Treatment of Solid Tumors

2021 ◽  
Vol 22 (5) ◽  
pp. 2608
Author(s):  
Ryuhjin Ahn ◽  
Josie Ursini-Siegel
Keyword(s):  
Cancer Treatment ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Tumor Microenvironments ◽  
Tumor Immunogenicity ◽  
Cancer Immunotherapies

Oncogenic kinases contribute to immunosuppression and modulate the tumor microenvironment in solid tumors. Increasing evidence supports the fundamental role of oncogenic kinase signaling networks in coordinating immunosuppressive tumor microenvironments. This has led to numerous studies examining the efficacy of kinase inhibitors in inducing anti-tumor immune responses by increasing tumor immunogenicity. Kinase inhibitors are the second most common FDA-approved group of drugs that are deployed for cancer treatment. With few exceptions, they inevitably lead to intrinsic and/or acquired resistance, particularly in patients with metastatic disease when used as a monotherapy. On the other hand, cancer immunotherapies, including immune checkpoint inhibitors, have revolutionized cancer treatment for malignancies such as melanoma and lung cancer. However, key hurdles remain to successfully incorporate such therapies in the treatment of other solid cancers. Here, we review the recent literature on oncogenic kinases that regulate tumor immunogenicity, immune suppression, and anti-tumor immunity. Furthermore, we discuss current efforts in clinical trials that combine kinase inhibitors and immune checkpoint inhibitors to treat breast cancer and other solid tumors.

scholarly journals Expectations and Challenges of First-Line Maintenance Therapy for Advanced Ovarian Cancer

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 501
Author(s):  
Tadahiro Shoji ◽  
Chie Sato ◽  
Hidetoshi Tomabechi ◽  
Eriko Takatori ◽  
Yoshitaka Kaido ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Checkpoint ◽  
Clinical Studies ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Ovarian Cancer ◽  
Targeted Drugs ◽  
First Line ◽  
Double Blind ◽  
Platinum Based Chemotherapy

The incidence of ovarian cancer, which has had a poor prognosis, is increasing annually. Currently, the prognosis is expected to improve with the use of molecular-targeted drugs and immune checkpoint inhibitors as maintenance therapies after the first-line chemotherapy. The GOG218 and ICON7 studies reported the usefulness of bevacizumab and the SOLO-1 and PRIMA (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy) studies have reported the usefulness of olaparib and niraparib, respectively. The ATHENA study investigating the usefulness of rucaparib is currently ongoing. Although clinical studies of immune checkpoint inhibitors are lagging in the field of gynecology, many clinical studies using programmed death cell-1 (PD-1) and PD-1 ligand 1 (PD-L1) antibodies are currently ongoing. Some biomarkers have been identified for molecular-targeted drugs, but none have been identified for immune checkpoint inhibitors, which is a challenge that should be addressed in the future.

Sign in / Sign up

Export Citation Format

Share Document