Kirsten rat sarcoma G12C inhibitor treatment for a patient with relapsed metastatic lung adenocarcinoma: A case report

Abstract

BACKGROUND

Kirsten rat sarcoma viral oncogene homolog (KRAS) is a commonly identified oncogenic driver in solid tumors, especially in non-small cell lung cancer. Until recently, KRAS was believed to be impossible to target because it lacks adenosine triphosphate-binding domains or other regions that allow specific small-molecule inhibitors to act. In this report, we described using KRAS at glycine 12 to cysteine (G12C) inhibitors as posterior line therapy in a patient with relapsed metastatic lung adenocarcinoma carrying KRAS G12C mutation.

CASE SUMMARY

A 53-year-old Chinese man was treated with radical surgical resection for lung cancer in June 2014. Re-examination in June 2015 indicated postoperative recurrence with metastasis. The patient completed several courses of antitumor therapy, including pemetrexed and nedaplatin, bevacizumab with docetaxel and cisplatin, bevacizumab and pemetrexed, sintilimab and anlotinib, sintilimab and albumin-bound paclitaxel, and cadonilimab and docetaxel. In early May 2023, the patient developed a cough productive of bloody sputum and shortness of breath after exercise. The main adverse reactions associated with KRAS G12C inhibitor therapy were gastrointestinal reactions, which could be alleviated by daily oral ondansetron tablets.

CONCLUSION

After multiple-line treatment including chemotherapy, targeted therapy, and immunotherapy, disease control was achieved in a case of advanced pulmonary adenocarcinoma carrying the KRAS G12C mutation by mutation-specific inhibitor therapy, and the adverse reactions to the therapy were tolerable.

Keywords: Non-small cell lung cancer; Kirsten rat sarcoma G12C; Targeted therapy; Gene mutation; Case report

Core Tip: Non-small cell lung cancer represents 85% of all pulmonary malignancies globally. Kirsten rat sarcoma viral oncogene homolog (KRAS) is among the most common mutations observed in malignant tumors, with roughly 13% of pulmonary adenocarcinomas carrying the KRAS at glycine 12 to cysteine (G12C) mutation. In this case, the initial therapeutic strategies for KRAS G12C-mutant lung adenocarcinomas were similar to those for driver mutation-negative non-small cell lung cancer. Following relapse, with KRAS G12C inhibitor administration, the patient’s post-relapse progression-free survival reached 17 months. Subsequently, the patient’s disease progressed, necessitating renewed treatment with radiotherapy, chemotherapy, and targeted therapy.