Supplementary Material for: Sotorasib in KRAS p.G12C-mutated pulmonary sarcomatoid carcinoma - Therapeutic efficacy of a KRAS inhibitor in symptomatic brain metastases

Introduction Pulmonary sarcomatoid carcinomas (PSC) are a rare subgroup of non-small cell lung cancer (NSCLC). In contrast to other NSCLC pulmonary sarcomatoid carcinomas have a poor prognosis due to limited efficacy of radiation and chemotherapy. Therefore other therapeutic approaches are needed. KRAS mutations occur in PSC with a significant proportion of 30%, most of them are G12C with the therapeutic option of sotorasib. Case report Here we describe the case of a patient with PSC and pleural metastases. After first line chemotherapy the patient presented with new neurological symptoms such as a hemiparesis of the right arm and focal seizures. Following the detection of new brain metastases, we switched the therapy to sotorasib due to the presence of a KRAS G12C mutation. During treatment with sotorasib, the patient's condition worsened progressively and his neurological symptoms got more severe. A CCT performed during the course of treatment showed progression of the brain metastases. After 48 days being on drug, decision to discontinuate therapy with sotorasib due to patient’s inability to take oral medication and change to a best supportive care concept was made. The Patient died few weeks after termination of therapy with rapidly progressive disease. Discussion/Conclusion This case emphasizes the poor prognosis of patients with PSC due to a lack of therapeutic response to chemotherapy, radiation and, as seen in this case, current targeted therapy as well. Our case emphasizes the need to further evaluate therapeutic responses of targeted therapy in this rare subtype of NSCLC.