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Review
. 2024 Mar 28;16(7):1327.
doi: 10.3390/cancers16071327.

KRASG12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia

Kazushi Fujimoto  1 , Satoshi Ikeda  1 , Erina Tabata  1 , Taichi Kaneko  1 , Shinobu Sagawa  1 , Chieri Yamada  1 , Kosumi Kumagai  1 , Takashi Fukushima  1 , Sanshiro Haga  1 , Masayuki Watanabe  1 , Tatsuya Muraoka  1 , Akimasa Sekine  1 , Tomohisa Baba  1 , Takashi Ogura  1
Affiliations
Review

KRASG12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia

Kazushi Fujimoto et al. Cancers (Basel). .

Abstract

Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted therapies are lacking. KRAS mutations have been frequently detected in patients with NSCLC with comorbid IP. However, the low detection rate of common driver gene mutations, such as epidermal growth factor receptor and anaplastic lymphoma kinase, in patients with comorbid IP frequently results in inadequate screening for driver mutations, and KRAS mutations may be overlooked. Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRASG12C mutations. Although patients with comorbid IP were not excluded from clinical trials of these KRASG12C inhibitors, the incidence of drug-induced pneumonitis was low. Therefore, KRASG12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience.

Keywords: KRASG12C; acute exacerbation; cytotoxic drug; idiopathic pulmonary fibrosis; immune checkpoint inhibitor; interstitial pneumonia; non-small-cell lung cancer; pneumonitis; radiation therapy.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships that may be considered potential competing interests: Ikeda S reports receiving grants and personal fees from Chugai and AstraZeneca and personal fees from Ono, Bristol-Myers Squibb, and Pfizer outside of the submitted work. Ogura T reports receiving personal fees from Boehringer Ingelheim and Shionogi outside of the submitted work. All remaining authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Structural formulas of sotorasib and adagrasib.
Figure 2
Figure 2
Chest X-ray and chest computer tomography (CT) of the presented case: (A) chest X-ray at the initiation of sotorasib; (B,C) chest CT at the initiation of sotorasib; (D) chest X-ray 6 months after sotorasib; (E,F) chest CT 6 months after sotorasib.
See this image and copyright information in PMC

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