NEW YORK (Reuters Health) – KRASG12 C-mutant non-small-cell lung cancer (NSCLC) seems smoking-related and is likely targetable by inhibitors that can delay or prevent brain transition, according to an analysis of real-world outcomes.
” Currently, most of druggable oncogene-driven NSCLCs occur in non-smokers/light ex-smokers,” Dr. Wanyuan Cui of the Peter MacCallum Cancer Centre in Melbourne informed Reuters Health by email. “Nevertheless, as appealing covalent KRASG12 C inhibitors continue to develop, it is essential for all clients with NSCLC to go through early detailed genomic profiling, no matter smoking history, to look for this essential targetable mutation.”
Dr. Cui and coworkers analyzed data from patients enrolled in the Thoracic Malignancies Associate between 2012 to 2019 with recurrent/metastatic non-squamous NSCLC, readily available KRAS outcomes, and without EGFR/ALK/ROS1 gene aberrations. They compared clinicopathologic features, treatment and general survival for KRAS G12 C, KRAS wildtype (KRASwt), KRAS-mutated (KRASmut); and other KRAS (KRASother) mutations.
As reported in Lung Cancer, among 1,386 NSCLC patients, 1,040 were excluded due to non-metastatic/recurrent; unidentified KRAS status; ALK/EGFR/ROS1-positive status; or duplicates.
In General, 346 clients were analyzed: 144 (42%) were KRASmut, of whom 65 (45%) were KRAS G12 C. All patients with KRASG12 C were active or ex-smokers, versus 92%of KRASother and 83%of KRASWT.
The occurrence of brain metastases throughout follow-up was similar in between KRASmut and KRASwt (33%vs. 40%), and KRASG12 C and KRASother (40%vs. 41%).
The percentage of clients receiving one or multiple lines of systemic therapy was equivalent and overall survival was comparable in between KRASmut and KRASWT, and KRASG12 C and KRASother.
The authors conclude, “40%of clients with KRASG12 C NSCLC developed brain transition during follow up. Therefore, in this group of clients, treatments with excellent intracranial penetration have essential implications for long-term disease control. While we did not observe any prognostic impact of KRASG12 C mutations, the development of KRASG12 C targeted treatments, which have actually shown appealing early efficacy in KRASG12 C NSCLC, are anticipated to enhance results in the population.”
Dr. Cui stated, “Parallel to the lessons learned from EGFR- and ALK-aberrant NSCLC, agents that are effective for existing brain metastases, and that prevent or postpone brand-new brain metastases will be important for targeting KRASG12 C.”
” We did not discover differences in overall survival in between KRASG12 C and KRASother NSCLC, comparable to a previous U.S. research study, however different to a prior European research study,” she added. “Clients in our research study were mainly Caucasian (88%), and therefore our findings may not be generalizable to patients of different ethnic cultures worldwide.”
Dr. Joshua Sabari, an oncologist at NYU Langone Perlmutter Cancer Center in New York City who is involved in studies of KRASG12 C mutation inhibitors, told Reuters Health, “In the age of novel, active, and highly-potent KRASG12 C inhibitors such as MRTX849 and AMG510, information from this study support the development of targeted rehabs in this population.”
Particularly, he said by e-mail, the research study findings “solidify that KRASG12 C is a common alteration worthy of targeting. All patients identified to have KRASG12 C mutations were existing or former cigarette smokers, in line with what I see in my medical practice.”
” The activity of the KRAS G12 C inhibitors in the central nervous system remains unidentified,” he included. “Intracranial action rate will be crucial for the successful advancement of these agents, as over one quarter of patients in this research study presented with brain metastases at initial diagnosis.”
Like Dr. Cui, he said, “These data strengthen the value of unique KRASG12 C inhibitors currently being investigated in the center.”
SOURCE https://bit.ly/38 BAf23 Lung Cancer, online June 26, 2020.