Does denosumab offer survival benefits? Our experience with denosumab in metastatic non-small cell lung cancer patients treated with immune-checkpoint inhibitors.

Cao, Yunmeng; Afzal, Muhammad Zubair; Shirai, Keisuke

doi:10.1200/jco.2021.39.15_suppl.e21039

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…Another retrospective observational study evaluated the efficacy of anti-RANKL agents and ICIs in patients with stage IV NSCLC and skeletal metastases. This study, including 69 patients who received denosumab within 30 days of ICI therapy, suggested that an overlap in the duration of ICI and denosumab treatment for > 3 months is associated with improved OS and PFS in patients undergoing concomitant therapy 75 . Additionally, a study presented at the 22nd World Lung Cancer Congress in 2021 explored the efficacy of bone-targeted agents (BTAs) combined with ICIs in patients with advanced NSCLC and bone metastases.…”

Section: The Receptor Activator Of Nuclear Factor-κb Ligand (Rankl) I...mentioning

confidence: 87%

Repurposing drugs for solid tumor treatment: focus on immune checkpoint inhibitors

Liu,

Li,

Qin

et al. 2023

Cancer Biol Med

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Cancer remains a significant global health challenge with limited treatment options beyond systemic therapies, such as chemotherapy, radiotherapy, and molecular targeted therapy. Immunotherapy has emerged as a promising therapeutic modality but the efficacy has plateaued, which therefore provides limited benefits to patients with cancer. Identification of more effective approaches to improve patient outcomes and extend survival are urgently needed. Drug repurposing has emerged as an attractive strategy for drug development and has recently garnered considerable interest. This review comprehensively analyses the efficacy of various repurposed drugs, such as transforming growth factor-beta (TGF-β) inhibitors, metformin, receptor activator of nuclear factor-κB ligand (RANKL) inhibitors, granulocyte macrophage colony-stimulating factor (GM-CSF), thymosin α1 (Tα1), aspirin, and bisphosphonate, in tumorigenesis with a specific focus on their impact on tumor immunology and immunotherapy. Additionally, we present a concise overview of the current preclinical and clinical studies investigating the potential therapeutic synergies achieved by combining these agents with immune checkpoint inhibitors.

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Section: The Receptor Activator Of Nuclear Factor-κb Ligand (Rankl) I...mentioning

confidence: 87%

Repurposing drugs for solid tumor treatment: focus on immune checkpoint inhibitors

Liu,

Li,

Qin

et al. 2023

Cancer Biol Med

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“…This intricate dynamic creates an immunosuppressive environment, potentially leading to immunotherapy resistance within the bone. Prior retrospective studies investigating bone modifying agents such as bisphosphates or denosumab in addition to immunotherapy are yet to demonstrate any difference in survival outcomes for these patients [ 41 , 42 , 43 ]. A single-arm study of second-line nivolumab combined with denosumab demonstrated the efficacy of this combination [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Site-Specific Response and Resistance Patterns in Patients with Advanced Non-Small-Cell Lung Cancer Treated with First-Line Systemic Therapy

Brown,

Ahn,

Gao

et al. 2024

Cancers

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Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients with unresectable stage III/IV NSCLC who received first-line systemic therapy, we sought to assess the association between the site of metastases with patterns of response and progression. Data regarding demographics, tumour characteristics (including site, size, and volume of metastases), treatment, and outcomes were examined at two cancer care centres. The endpoints included organ site-specific response rate, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Two-hundred and eighty-five patients were included in the analysis. In a multivariate analysis, patients with bone metastases had a reduced ORR, PFS, and OS. Primary resistance was also more likely in patients with bone metastases. Patients with bone or liver metastases had a shorter OS when receiving ICIs with or without chemotherapy, but not with chemotherapy alone, suggesting an immunological basis for therapeutic resistance. A directed assessment of the tumour microenvironment in these locations and a deeper understanding of the drivers of organ-specific resistance to immunotherapy are critical to optimise novel combination therapies and sequencing in these patients.

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“…Hypocalcemia can occur as a manifestation of tumor lysis syndrome as well, which has been described with the use of both ICI and CAR-T cell therapies. Additionally, the use of denosumab (humanized mAb to RANK ligand) in combination with ICIs can increase the likelihood of hypocalcemia (83).…”

Section: Hypocalcemiamentioning

confidence: 99%

Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy

Uppal

Workeneh

Rondon‐Berrios

et al. 2022

CJASN

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Novel immunotherapy drugs have changed the landscape of cancer medicine. Immune checkpoint inhibitors and chimeric antigen receptor T cells are being used and investigated in almost all solid cancers. Immune-related adverse events have been associated with immunotherapies. Acute kidney injury has been the most commonly associated kidney adverse event. In this review, we showcase the several associated electrolyte disorders seen with immunotherapy. Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common. Endocrine causes of hyponatremia are rare. Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis. Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations including immune checkpoint inhibitor-induced parathyroid hormone - related peptide production, sarcoid-like granulomas, and hyper-progression of the disease. Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor-induced tumor lysis syndrome. Chimeric antigen receptor T cell therapy-associated electrolyte disorders are also common. This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur. Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.

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Does denosumab offer survival benefits? Our experience with denosumab in metastatic non-small cell lung cancer patients treated with immune-checkpoint inhibitors.

Cited by 3 publications

References 8 publications

Repurposing drugs for solid tumor treatment: focus on immune checkpoint inhibitors

Repurposing drugs for solid tumor treatment: focus on immune checkpoint inhibitors

Site-Specific Response and Resistance Patterns in Patients with Advanced Non-Small-Cell Lung Cancer Treated with First-Line Systemic Therapy

Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy

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