Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial

Atkins, Michael B.; Plimack, Elizabeth R.; Puzanov, Igor; Fishman, Mayer; McDermott, David F.; Cho, Daniel C.; Vaishampayan, Ulka N.; George, Saby; Olencki, Thomas; Tarazi, Jamal; Rosbrook, Brad; Fernandez, Kathrine C.; Lechuga, Mariajosé; Choueiri, Toni K.

doi:10.1016/s1470-2045(18)30081-0

Cited by 324 publications

(230 citation statements)

References 33 publications

(43 reference statements)

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“…This finding led to discontinuation of further study of these combinations in clinical trials . In contrast, axitinib a more selective inhibitor of the vascular endothelial growth factor receptor with a lower known risk for hepatotoxicity as a single agent compared to sunitinib or pazopanib, demonstrated a lower rate of severe hepatotoxicity …”

Section: Clinical Trials Of Icis: Results Of Risk For Hepatotoxicitymentioning

confidence: 99%

Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

Suzman

Pelosof

Rosenberg

et al. 2018

Liver International

188

151

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Immune checkpoint inhibitors (ICIs) block CTLA-4, PD-1 and PD-L1, or other molecules that control antitumour activities of lymphocytes. These products are associated with a broad array of immune-related toxicities affecting a variety of organs, including the liver. ICI-associated immune-mediated hepatitis (IMH) ranges in severity between mild and life-threatening and is marked by findings that bear both similarities as well as differences with idiopathic autoimmune hepatitis. Hepatotoxic events are often detected in clinical trials of ICIs that are powered for efficacy. Risk levels for ICI-induced liver injury may be impacted by the specific checkpoint molecule targeted for treatment, the ICI dose levels, and the presence of a pre-existing autoimmune diathesis, chronic infection or tumour cells which infiltrate the liver parenchyma. When patients develop liver injury during ICI treatment, a prompt assessment of the cause of injury, in conjunction with the application of measures to optimally manage the adverse event, should be made. Strategies to manage the risk of IMH include the performance of pretreatment liver tests with regular monitoring during and after ICI treatment and patient education. Using Common Terminology Criteria for Adverse Events developed at the National Cancer Institute to measure the severity level of liver injury, recommended actions may include continued ICI treatment with close patient monitoring, ICI treatment suspension or discontinuation and/or administration of corticosteroids or, when necessary, a non-steroidal immunosuppressive agent. The elucidation of reliable predictors of tumour-specific ICI treatment responses, as well as an increased susceptibility for clinically serious immune-related adverse events, would help optimize treatment decisions for individual patients.

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Section: Clinical Trials Of Icis: Results Of Risk For Hepatotoxicitymentioning

confidence: 99%

Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

Suzman

Pelosof

Rosenberg

et al. 2018

Liver International

188

151

View full text Add to dashboard Cite

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“…These monoclonal antibodies targeting immune checkpoints (PD1 and PD-L1), by their role in restoring the antitumor immunity through the reversal of immune escape or evasion, have led to a significant antitumor activity with confirmed impact on the duration of tumor response and prolonged overall survival. They have earned fast approvals across multiple cancer subtypes including melanoma, lung cancer, urological tumors, breast cancer and other solid tumors [16][17][18][19][20]. More importantly, these agents have earned several indications as monotherapy without association to chemotherapeutic agents, thus predisposing cancer patients to a different and more tolerable toxicity profile [16,17,19,21].…”

Section: Role Of Icis In Cancermentioning

confidence: 99%

Do checkpoint inhibitors compromise the cancer patients’ Immunity and Increase the Vulnerability to COVID-19 Infection?

Kattan

Assi

2020

Immunotherapy

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Since we are not able to consider ICIs treatment as highly immunosuppressive, avoiding it in cancer patients to reduce coronavirus infections could deprive these patients from a highly active class of drugs. "The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has been declared a pandemic by the WHO that claimed the lives of thousands of people within a few months. Cancer patients represent a vulnerable population due to the acquired immunodeficiency associated with anti-cancer therapy. Immune checkpoint inhibitors have largely impacted the prognosis of a multitude of malignancies with significant improvement in survival outcomes and a different, tolerable toxicity profile. In this paper, we assess the safety of ICI administration in cancer patients during the coronavirus pandemic in order to guide the usage of these highly efficacious agents.

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“…In a phase I study, PD‐L1 blockade with atezolizumab showed promising antitumor activity with a manageable safety profile . Recent clinical trials for advanced RCC seemed to focus on combination therapy . They included combination regimens with two ICIs, such as nivolumab plus ipilimumab, and those with ICIs and angiogenesis inhibitors, such as pembrolizumab plus axitinib, and avelumab plus axitinib …”

Section: Biomarkers For Immune Checkpoint Therapymentioning

confidence: 99%

Current status of prognostic factors in patients with metastatic renal cell carcinoma

et al. 2019

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In recent years, the induction of novel agents, including molecular‐targeted agents and immune checkpoint inhibitors, have dramatically changed therapeutic options and their outcomes for metastatic renal cell carcinoma. Several prognostic models based on the data of patients with metastatic renal cell carcinoma treated with targeted agents or cytokine therapy have been useful in real clinical practice. Serum or peripheral blood markers related to inflammatory response have been reported to be associated with their prognosis or therapeutic efficacy. In addition to them, investigation for novel predictive factors that represent the efficacy of agents, the risk of adverse events and the prognosis are required for the advance of therapeutic strategies. The present review discusses the conventional prognostic models and clinical factors, and recent advances of the identification of some of the most promising molecules as novel biomarkers for metastatic renal cell carcinoma.

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Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial

Abstract: Pfizer Inc.

Cited by 324 publications

References 33 publications

Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents

Do checkpoint inhibitors compromise the cancer patients’ Immunity and Increase the Vulnerability to COVID-19 Infection?

Current status of prognostic factors in patients with metastatic renal cell carcinoma

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