Sotorasib Found to Have Promising Intracranial Activity in Patients with NSCLC with Brain Metastasis

Web Exclusives —April 19, 2023


Lung Cancer

KRAS G12C mutations occur in approximately 14% of patients with non–small-cell lung cancer (NSCLC). These mutations are responsive to KRAS G12C inhibitors, including sotorasib, which is the first drug approved for the treatment of metastatic NSCLC harboring the KRAS G12C mutation. Patients with this tumor type have an approximately 40% lifetime incidence of brain metastases. However, effective treatment for central nervous system metastases is an unmet need in this patient population. Sotorasib has a response rate of 28% to 37% in patients with KRAS G12C NSCLC, with a median progression-free survival (PFS) of 5.6 to 6.8 months. Although brain metastases are common in patients with KRAS G12C NSCLC, published clinical trials of sotorasib have excluded these patients from participation.

Not much is known about the efficacy of sotorasib on the central nervous system. Lamberti and colleagues investigated this unmet need and recently released their results. They identified 899 patients who had received a diagnosis of metastatic NSCLC harboring the KRAS G12C mutation. Of these patients, 316 had brain metastases that occurred within 3 months of the initial diagnosis. Patients with KRAS G12C–mutated NSCLC without brain metastases had a 16.0-month overall survival, whereas those with brain metastases had a 13.2-month overall survival. No difference was seen in programmed cell death ligand 1 tumor proportion score or tumor mutational burden between the 2 patient groups.

The investigators identified 6 patients who developed active, untreated brain metastases before sotorasib was initiated. All 6 of these patients underwent magnetic resonance imaging (MRI) prior to starting treatment. One patient had disease progression and died 3 weeks after sotorasib initiation. The remaining 5 patients had ≥1 subsequent MRI while receiving sotorasib. One patient who had 5 nonmeasurable brain lesions at baseline MRI had resolution of 4 of these 5 lesions after sotorasib treatment. The remaining 4 patients had measurable disease, with 3 of the patients having a response to treatment. The median duration of response to sotorasib treatment was 4.1 months in these 3 patients, and the median PFS was 4.7 months. Of the 4 remaining patients, 1 was still receiving sotorasib treatment at study publication with an ongoing response of 7 months. A second patient had objective intracranial response along with systemic disease improvement, but the intracranial disease progressed while the systemic disease remained controlled. The third patient had an initial response both with brain lesions and systemically but had isolated intracranial progression with systemic response continuing. The final patient had both systemic and intracranial disease progression.

Source: Lamberti G, Aizer A, Ricciuti B, et al. Incidence of brain metastases and preliminary evidence of intracranial activity with sotorasib in patients with KRASG12C-mutant non–small-cell lung cancer. JCO Precis Oncol. 2023;7:e2200621.

Related Articles
Sotorasib Conveys Long-Term Benefits in Patients With KRAS G12C–Mutated Non–Small Cell Lung Cancer
Web Exclusives
Analysis of the long-term results of the CodeBreak 100 clinical trial showed that sotorasib demonstrated long-term efficacy, in particular among patients with low initial circulating tumor DNA values.
NGS Testing More Cost-Effective Than SGT in Oncology
Web Exclusives
A recent study showed that next-generation sequencing testing has superior cost benefit when compared with single-gene testing for multiple cancer types, including non–small cell lung cancer.
Phase 3 Study of Sotorasib in NSCLC Demonstrated Shorter PFS Than Phase 1/2 Trials
Web Exclusives
Analysis of the phase 3 study of sotorasib in patients with non–small cell lung cancer found faster time to response compared with docetaxel but a shorter progression-free survival than what was seen in the phase 1/2 trials.
Last modified: August 10, 2023

Subscribe Today!

To sign up for our print publication or e-newsletter, please enter your contact information below.

I'd like to receive:

  • First Name *
    Last Name *
    Profession or Role
    Primary Specialty or Disease State