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Cited by 19Lung Cancer Treatments and MutationsCancer Immunotherapy and BiomarkersLung Cancer Diagnosis and Treatment

The toxicity associated with combining immune check point inhibitors with tyrosine kinase inhibitors in patients with non-small cell lung cancer

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Kalra, Anjali, Rashdan, Sawsan·2023·Frontiers in Oncology
DOI 10.3389/fonc.2023.1158417PMC PMC10140561
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Abstract

Latest advances in non-small cell lung cancer (NSCLC) therapies have revolutionized the treatment regimens utilized for NSCLCs with or without a driver mutation. Molecular targeted treatments such as tyrosine kinase inhibitors (TKIs) are utilized to prevent tumor progression and improve survival. Despite the great benefit of immunotherapy in NSCLC tumors with no driver mutation, the use of immune checkpoint inhibitors (ICIs) in NSCLC tumors harboring a driver mutation has been under debate. Furthermore, several trials have been conducted investigating the use of these therapies with TKIs. A few trials were halted due to growing concerns of increased toxicity with the combination of TKI and immunotherapy. The adverse events ranged from low grade dermatologic complaints to fatal interstitial lung diseases. These toxicities occur with both concurrent and sequential administration of treatment. Thus, recommendations for the safest method of combination treatment have not yet been described. This review paper discusses recent views on combination treatment, previous clinical trials reporting grade 3-4 toxicities, and guidelines for a safe timeline of administration of treatment based on past evidence.

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  • Side effects observed with sunitinib plus nivolumab were consistent with those reported for most immunotherapy and TKI combinations.

    “Side effects observed with sunitinib plus nivolumab were consistent with those reported for most of immunotherapy and TKI combinations. 50”

    From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [50]

    The 'Incidence and type of toxicity' section reports adverse effects for several immunotherapy–TKI combinations, but not sunitinib plus nivolumab. A search for sunitinib found no passage in our copy assessing that combination or comparing its side effects with those of other combinations. Page numbers were not available. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

  • An increased number of tumor-infiltrating T cells and PD-L1 expression in metastases compared with primary tumors was shown in osteosarcoma.

    “An increased number of tumor‐infiltrating T cells and PD‐L1 expression in metastases as compared with primary tumors was shown in osteosarcoma, 50”

    From Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial (2025) · cites this paper as [50]

    The Introduction (page unavailable) discusses PD-L1 expression in EGFR-mutant lung cancer, not osteosarcoma. Searches for osteosarcoma and for tumor-infiltrating T cells in metastases versus primary tumors found no passage addressing the claimed comparison. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 43

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Authors
Kalra, A., & Rashdan, S.
Affiliations
Harold C. Simmons Comprehensive Cancer Center (US)
Corresponding author
Rashdan, Sawsan
ORCID
Kalra, Anjali
Venue
Frontiers in Oncology
Publisher
Frontiers Media SA
Published
2023-04-14
Volume
13
Pages
1158417-1158417
ISSN
2234-943X (ISSN-L)
DOI
10.3389/fonc.2023.1158417
PMC
PMC10140561
OpenAlex
W4365516770
Cited by
19
References
50
Citations by year
2026: 5 · 2025: 5 · 2024: 8 · 2023: 1
FWCI
0.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
non-small cell lung cancer, immune checkpoint inhibitors, tyrosine kinase inhibitors, combination therapy, drug toxicity, interstitial lung disease, dermatologic adverse events, driver mutations

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