Case Report: Severe Hepatitis With Sotorasib After Immunotherapy

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A case report of life-threatening hepatitis in a lung cancer patient suggests caution when using second-line sotorasib in patients previously treated with checkpoint inhibitors.
A case report of life-threatening hepatitis in a lung cancer patient suggests caution in using second-line treatment with the newly approved targeted agent sotorasib (Lumakras) in patients who have previously been treated with checkpoint inhibitor (CPI) immunotherapy such as pembrolizumab (Keytruda).

"Our case…represents an unexpected high-grade hepatic toxicity [with sotorasib]," say the authors, led by Parvin Begum, MBChB, Royal Marsden NHS Foundation Trust, London, United Kingdom. They suspect that sotorasib triggered CPI immune-related hepatitis, even though treatment with the CPI had been stopped 14 weeks prior.

Sotorasib is the first drug to target KRAS mutations in non-small cell lung cancer (NSCLC). These are the most common mutations in lung cancer, but were long considered to be 'undruggable.' This product specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations. Its approval this past May was hailed as a 'historic milestone.'

The case report was published in JTO Clinical and Research Reports.

"We report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis," the investigators write.

"Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity," they comment.

The case involved a 62-year-old male patient with KRAS G12C mutant NSCLC. He was initially treated with a carboplatin-pemetrexed-pembrolizumab regimen, but his disease progressed after only one cycle of maintenance pembrolizumab-pemetrexed. He was subsequently treated with palliative radiotherapy.

Treatment with the immune checkpoint inhibitor pembrolizumab had…
Pam Harrison
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