The LEAP Program: Lenvatinib Plus Pembrolizumab for the Treatment of Advanced Solid Tumors

Taylor, Matthew H.; Schmidt, Emmett V.; Dutcus, Corina E.; Pinheiro, Elaine M.; Funahashi, Yasuhiro; Lubiniecki, Gregory M.; Rasco, Drew W.

doi:10.2217/fon-2020-0937

Cited by 47 publications

(35 citation statements)

References 29 publications

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“…This suggests a profound effect of lenvatinib on the microenvironment leading to increased pembrolizumab activity. In the gastric/esophageal arm of the LEAP study, the combination showed more modest benefits with a response rate of 39% and PFS of 7.4 months [35]. This combination will be tested further in the future.…”

Section: Combination With Lenvatinibmentioning

confidence: 96%

Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer

Siddiqui

Almhanna

2021

Cancers

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Together, gastric cancer and esophageal cancer (EC) possess two of the highest incidence rates amongst all cancers. They exhibit poor prognoses in which the 5-year survival rate is dismal. In addition to cytotoxic chemotherapy, treatment efforts have been geared toward targeting human epidermal growth factor receptor 2 (HER-2), vascular endothelial growth factor (VEGF), and programmed death ligand-1 (PD-1). Although ample success has been recorded with these agents, gastric and esophageal cancer remain lethal, and further research into potential treatment alternatives is needed. In this article, we will review some of the targets at the forefront of investigation such as claudin, Dickkopf-related protein 1 (DKK-1), fibroblast growth factor receptor (FGFR), and matrix metalloproteinases (MMPs). These innovative target pathways are in the midst of clinical trials to be implemented in the treatment algorithm for this patient population. Ultimately, exploiting the oncogenic tendencies of these potential biomarkers creates an opportunity for precise treatment and improved prognosis for these cancers. Lastly, research aimed toward reversing PD-1 antibodies resistance by combining it with other novel agents or other treatment modalities is underway in order to expand existing treatment options for this patient population.

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Section: Combination With Lenvatinibmentioning

confidence: 96%

Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer

Siddiqui

Almhanna

2021

Cancers

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“…When local disease control is needed for advanced disease, TACE may be indicated for use alone or in combination with systemic therapy. A current phase III study is evaluating TACE in combination with Lenvatinib and Pembrolizumab for advanced, non-metastatic disease[ 37 ]. In addition to being useful in stratifying patients to appropriate treatment, BCLC class is a useful tool in prognosticating survival following TACE, with many studies stratifying survival based on these categories.…”

Section: Tacementioning

confidence: 99%

Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons

Makary¹,

Ramsell²,

Miller³

et al. 2021

WJG

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Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.

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“…Further studies are therefore needed to elucidate the role of FGFRs in modulating tumor immune response. Interestingly, combination of FGFR inhibitors and immunotherapy showed promising therapeutic effect in multiple solid tumors in clinical trials [137][138][139], and the underlying mechanisms of action still need to be fully understood.…”

Section: Fibroblast Growth Factor Receptorsmentioning

confidence: 99%

“…Figure 3 shows the role of other oncogenes to regulate PD-L1 expression in cancer cells including c-Myc, p53, EML4-ALK, K-ras and EGFR. tion of FGFR inhibitors and immunotherapy showed promising therapeutic effect in multiple solid tumors in clinical trials [137][138][139], and the underlying mechanisms of action still need to be fully understood.…”

Section: Epidermal Growth Factor Receptormentioning

confidence: 99%

The Role of Oncogenes and Redox Signaling in the Regulation of PD-L1 in Cancer

Glorieux

Xia

Huang

2021

Cancers

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Tumor cells can evade the immune system via multiple mechanisms, including the dysregulation of the immune checkpoint signaling. These signaling molecules are important factors that can either stimulate or inhibit tumor immune response. Under normal physiological conditions, the interaction between programmed cell death ligand 1 (PD-L1) and its receptor, programmed cell death 1 (PD-1), negatively regulates T cell function. In cancer cells, high expression of PD-L1 plays a key role in cancer evasion of the immune surveillance and seems to be correlated with clinical response to immunotherapy. As such, it is important to understand various mechanisms by which PD-L1 is regulated. In this review article, we provide an up-to-date review of the different mechanisms that regulate PD-L1 expression in cancer. We will focus on the roles of oncogenic signals (c-Myc, EML4-ALK, K-ras and p53 mutants), growth factor receptors (EGFR and FGFR), and redox signaling in the regulation of PD-L1 expression and discuss their clinical relevance and therapeutic implications. These oncogenic signalings have common and distinct regulatory mechanisms and can also cooperatively control tumor PD-L1 expression. Finally, strategies to target PD-L1 expression in tumor microenvironment including combination therapies will be also discussed.

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The LEAP Program: Lenvatinib Plus Pembrolizumab for the Treatment of Advanced Solid Tumors

Cited by 47 publications

References 29 publications

Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer

Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer

Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons

The Role of Oncogenes and Redox Signaling in the Regulation of PD-L1 in Cancer

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