The novel KRAS inhibitor divarasib has shown promise in previously treated patients with advanced solid tumors harboring a KRAS G12C mutation.

An analysis of the KRYSTAL-1 study indicates that adagrasib has intracranial activity in people with KRAS G12C-mutated non-small-cell lung cancer and untreated CNS metastases.

Patients with previously treated KRAS G12C-mutated advanced non-small-cell lung cancer have significantly better progression-free survival and objective response rates with sotorasib than with docetaxel, research shows.

Melissa Johnson provides an overview of the CodeBreaK 200 study pitting sotorasib against docetaxel in patients who have received prior treatment for non-small-cell lung cancer with KRAS G12C mutations.

A large US study has shown the feasibility of circulating tumor DNA analysis to detect KRAS G12C mutations in patients with solid tumors.

For example, KRAS mutations were associated with resistance to EGFR inhibitors in advanced NSCLC, with a significant gene-by-treatment hazard ratio (HR) for death of 1.86.

High tumor mutational burden is associated with a better response to immune checkpoint inhibitors in people with non-small-cell lung cancer across all levels of PD-L1 expression, US researchers report.

There were no significant associations between NLR and selected variants of interest, namely EGFR , KRAS , TP53 , KEAP1 , STK11 , SMARCA4 , ARID1A , and targeted DNA damage response and repair genes.

And we were doing PCR to look at KRAS, to look at EGFR, and then we had new biomarkers coming.

The KRAS G12C inhibitor sotorasib has durable efficacy and manageable safety in previously treated patients with KRAS -mutated, advanced non-small-cell lung cancer, suggests long-term follow-up of the CodeBreaK 100 trial.

US researchers have identified diverse molecular and histologic mechanisms of acquired resistance to KRAS G12C inhibitors in people with cancer.

Ferdinandos Skoulidis presents an update from the CodeBreaK 100 trial of sotorasib in previously treated patients with non-small-cell lung cancer and KRAS G12C mutations, focusing on overall survival data and a subgroup analysis by co-mutations.

The presence of KRAS G12C mutations needs to be determined by an FDA-approved test, and the agency has also approved the QIAGEN therascreen ® KRAS RGQ PCR kit (QIAGEN, Venlo, Netherlands) and the Guardant360® CDx assay (Guardant Health Inc, Redwood City, California, USA) as companion diagnostics for use in tissue and plasma samples, respectively.

Adagrasib could play a role in the treatment of advanced non-small-cell lung cancer with a KRAS G12C mutation, indicates early research presented at the European Lung Cancer Virtual Congress 2021.

The KRAS inhibitor sotorasib achieves clinical benefit in individuals who have received prior treatment for advanced non-small-cell lung cancer harboring a KRAS G12C mutation, suggest data from the phase 2 cohort of CodeBreaK 100.

In the absence of other satisfactory treatment options, the panel “strongly” recommends that clinicians should give PD-1 inhibitor therapy, such as pembrolizumab, to patients who test positive for MSI/dMMR, and the TRK inhibitors larotrectinib or entrectinib to those with NTRK fusions.

Conversley, the response to ensartinib was generally nonexistent in the very small number of patients with alterations in genes that could mediate bypass signaling pathways (eg, EGFR , KRAS , PIK3CA , and ERBB2 ).

In addition to these, alterations were seen in a diverse range of genes such as HER2 , BRAF , KRAS , and PIK3CA , at rates of 1–7%.

The remaining patients developed “unexpected” resistance mechanisms, with individual reports of RET , FGFR3 , and BRAF fusions and a KRAS Q61K mutation.

For example, what if the FDA had approved selumetinib in patients with advanced KRAS mutant lung adenocarcinoma based on its highly positive phase II randomized trial results?