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Review
. 2023 Apr 14:13:1158417.
doi: 10.3389/fonc.2023.1158417. eCollection 2023.

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

Anjali Kalra  1 , Sawsan Rashdan  2
Affiliations
Review

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

Anjali Kalra et al. Front Oncol. .

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.

Keywords: combination; immunotherapy; lung cancer; pneumonitis; toxicity; tyrosine kinase inhibitors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Percentage of Grade 3-4 Toxicities in Concurrent vs Sequential ICI and TKI Treatment.
Figure 2
Figure 2
Timeline of Toxicity with Administration of TKI in Relation to ICI Administration.
Figure 3
Figure 3
Treatment of Toxicity.
Figure 4
Figure 4
Tips for ICI treatment followed by TKI therapy.
See this image and copyright information in PMC

References

    1. Mamdani H, Matosevic S, Khalid AB, Durm G, Jalal SI. Immunotherapy in lung cancer: current landscape and future directions. Front Immunol (2022) 13:823618. doi: 10.3389/fimmu.2022.823618 - DOI - PMC - PubMed
    1. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. . Osimertinib in untreated EGFR-mutated advanced non-Small-Cell lung cancer. N Engl J Med (2018) 378(2):113–25. doi: 10.1056/NEJMoa1713137 - DOI - PubMed
    1. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim D-W, et al. . Alectinib versus crizotinib in untreated ALK-positive non–Small-Cell lung cancer. N Engl J Med (2017) 377(9):829–38. doi: 10.1056/NEJMoa1704795 - DOI - PubMed
    1. Shaw AT, Bauer TM, De Marinis F, Felip E, Goto Y, Liu G, et al. . First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med (2020) 383(21):2018–29. doi: 10.1056/NEJMoa2027187 - DOI - PubMed
    1. Wolf J, Seto T, Han J-Y, Reguart N, Garon EB, Groen HJM, et al. . Capmatinib inMETExon 14–mutated orMET-amplified non–Small-Cell lung cancer. N Engl J Med (2020) 383(10):944–57. doi: 10.1056/NEJMoa2002787 - DOI - PubMed