Herbert Loong, Advisor at Greater Bay Area International Clinical Trial Institute, shared on LinkedIn:
“Throwback: KRAS G12C in Asia, and why the landscape still matters.
In 2020, the KRAS G12C story was just beginning. AMG 510 (now sotorasib) had produced its first phase 1 responses in NSCLC and received FDA fast-track designation.
Our team asked a practical question: how common is this target and in which cancers?
We analysed next-generation sequencing data from 11,951 tumour samples collected across multiple centres in China. (Translational Lung Cancer Research, 2020).
What we found:
- KRAS mutations were present in 16.6% of samples. G12C made up 14.5% of these, or 2.4% of the whole cohort.
- G12C was most common in lung (4.3%), colorectal (2.5%) and biliary tract (2.3%) cancers. Within lung cancer, it was the leading KRAS subtype (35.9%).
- KRAS mutation rates differed from Western (COSMIC) data. They were lower in lung cancer and higher in pancreatic, colorectal and gastric cancers.
In lung adenocarcinoma, KRAS mutations were significantly more frequent in former and current smokers than in never-smokers.
99.5% of G12C tumours carried co-alterations, with a median of 14. TP53 was the most frequent. STK11 appeared in 18% of LUAD cases, and PIK3CA was more common in CRC than in LUAD. We suggested these differences could help explain why early G12C inhibitor activity looked so different in lung and colorectal cancer.
Why revisit this in 2026?
The field has changed considerably:
- Multiple KRAS G12C inhibitors are now approved, including several developed and approved in China, so access for our patients has expanded.
- In colorectal cancer, the field moved from G12C monotherapy to combinations with anti-EGFR therapy, reflecting the biology differences between tumour types.
- Trials are testing first-line combinations and next-generation RAS(ON) and pan-RAS inhibitors, which raises new questions about patient selection.
- Co-mutations such as STK11 and KEAP1 are central to how we interpret outcomes in KRAS-mutant lung cancer.
Each of these developments relies on population-specific data on prevalence and co-alterations. Those data determine trial feasibility in Asia, the expected yield of testing, and which patients may have primary resistance. The G12C signal in biliary cancers also supports comprehensive NGS beyond lung cancer.
Large real-world datasets do not replace prospective trials, but they do inform them.
I’m grateful to my co-authors, including Tony Mok and Lunxu Liu, and to colleagues across the participating centres and OrigiMed.”
Title: KRAS G12C mutations in Asia: a landscape analysis of 11,951 Chinese tumor samples
Authors: Herbert Ho-Fung Loong, Nan Du, Chunyan Cheng, Hanqing Lin, Jian Guo, Gen Lin, Mingjiang Li, Tao Jiang, Zhihua Shi, Yanzhi Cui, Xianfeng Jin, Jicheng Yao, Yutong Xing, Ming Yao, Kai Wang, Tony S. K. Mok, Lunxu Liu.
You can also read: Inside Setidegrasib’s Phase 3 Development: Targeting KRAS G12D Through Protein Degradation.
