Treatment Strategies for Managing Hepatotoxicity and Brain Metastases in KRAS G12C-Mutated NSCLC

Narjust Florez, MD, discusses KRAS G12C mutated non-small cell lung cancer, a subset of KRAS mutations which comprises 14% of NSCLC cases.

Dr Narjust Florez outlines FDA-approved firstline therapy options for KRAS G12C mutated non-small cell lung cancer, and notes most patients progress and require second line targeted therapy.

Dr Narjust Florez discusses the KRYSTAL-1 trial, focusing on the effectiveness and side effects of adagrasib in treating patients with NSCLC and KRASG12C mutations, and noting their impact on progression-free and overall survival.

KRYSTAL-7 is a study exploring the efficacy of adding adagrasib to first-line pembrolizumab in patient with NSCLC with varying PD-L1 expression levels, showing promising response rates and progression-free survival, but also adverse events like hepatotoxicity.

CodeBreaK 100 compares the safety and efficacy of pembrolizumab combined with adagrasib or sotorasib in treating KRAS G12C NSCLC, noting sotorasib has a longer presence and familiarity in clinical use.

Dr Narjust Florez discusses the hepatoxicity associated with KRAS G12C inhibitors, noting both adagrasib and sotorasib pose liver damage risks, but real-world data suggests adagrasib may have a lower risk; she emphases the importance of considering other causes of hepatoxicity before attributing it solely to these therapies.

Dr Narjust Florez discusses the higher incidence of hepatotoxicity with sotorasib as shown in real-world data, and suggests adagrasib as a preferable option for patients with pre-existing liver dysfunction or inflammation, highlighting the need to consider patient history and liver function when choosing KRAS inhibitors.

Narjust Florez, MD, emphasizes the importance of treating CNS metastases in KRAS G12C mutated NSCLC, highlighting the promising but limited data on adagrasib’s CNS penetrance and intracranial response, as shown in the KRystal-1b study, making it a preferred option for patients with CNS metastases despite its associated side effects.

Narjust Florez, MD, discusses the complexities of treating KRAS mutations in NSCLC, including the challenges of commutations affecting immunotherapy response, the need for prolonged progression-free survival with KRAS inhibitors, dosage considerations, and highlights ongoing unmet needs and future research directions.

Narjust Florez, MD, and Sandip P. Patel, MD, cohosted a X chat centering on treatment options for KRAS G12C non–small cell lung cancer.