What Does a KRAS G12C Mutation Mean?

This page is for people who see "KRAS G12C" on a biomarker or molecular report. It explains what the result means, which drugs target it, and what it does not tell you.

KRAS is a gene. It makes a small protein that acts as an on-off switch for cell growth. G12C names one exact change. At codon 12 (one small spot in the gene's code), the amino acid glycine has been swapped for cysteine. NCI calls sotorasib and adagrasib two of the first drugs made for this exact change to show benefit.

The number changes a lot by cancer type, and it is worth knowing which one applies.

In lung cancer, NCI reports KRAS variants (gene changes) in 25% to 30% of nonsquamous non-small cell lung cancer (NSCLC). G12C is the most frequent single one. It makes up roughly 13% of lung adenocarcinomas.

In colorectal cancer, NCI reports KRAS G12C in about 4% of cases, and notes it carries a poor prognosis.

Other cancers can carry it, but far less often. NCI's drug summaries list approved uses only in lung and colorectal cancer. Clinical trials are the route there.

Two drugs block KRAS G12C directly. Both are tablets. Both drug labels say the variant must be confirmed by an FDA-approved test. It is reasonable to ask which sample was tested, tumor tissue or blood, and which test was used.

Sotorasib, sold as Lumakras, is 960 mg by mouth once daily. Adagrasib, sold as Krazati, is 600 mg by mouth twice daily. Both can be swallowed with or without food. Those are the approved label amounts, given here once so the figure on your own prescription looks familiar. Your oncologist may write something different, or pause and restart at a lower amount if side effects call for it, and their instruction is the one to follow.

For lung cancer, each is approved on its own. The label wording is the same for both. It covers locally advanced or metastatic NSCLC with a KRAS G12C variant. It applies to adults who have had at least one prior systemic therapy (a drug treatment that travels through the whole body). So this is a later-line option, not a first move.

The response figures come from single-arm trials, meaning there was no comparison group. In CodeBreaK 100, sotorasib gave an overall response rate of 37.1% among 124 evaluable patients. The median duration of response was 11.1 months. In the KRYSTAL-1 lung cohort, adagrasib gave a confirmed response rate of about 43% among 112 patients. The median duration of response was 8.5 months. Almost everyone in that cohort had already had chemotherapy and immunotherapy.

In the bowel, neither drug is used alone. Sotorasib is paired with panitumumab. Adagrasib is paired with cetuximab. Both partners are anti-EGFR antibodies. These are lab-made proteins that block another growth signal called EGFR.

NCI gives the reason plainly. EGFR reactivation is a known resistance route to KRAS G12C blockade. Shutting KRAS alone lets the cell go around the block. The antibody closes that path.

The evidence is stronger here than in lung, because the trial was randomized (people were assigned to groups by chance). CodeBreaK 300 split 160 people with treated metastatic colorectal cancer into three arms. Median progression-free survival (the typical time before the cancer grew) was 5.6 months with the full daily amount of sotorasib plus panitumumab. It was 3.9 months with a reduced amount of sotorasib plus panitumumab. It was 2.2 months with standard care. Objective response was 26.4%, 5.7%, and 0%.

Both labels restrict this to people who have already had fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Both lung indications, and the adagrasib colorectal indication, came through the FDA's accelerated approval pathway. The labels say so directly.

That pathway lets a drug reach patients on response rate and duration alone. Survival data do not yet exist. Continued approval may depend on confirmatory trials showing real benefit. This is not a lesser drug. It is a lesser stage of evidence. The difference is worth naming out loud.

G12C is one KRAS change among many. The two approved drugs are approved only for G12C. So "KRAS mutation" and "KRAS G12C" are not interchangeable words on a report, and it is worth confirming which one is written.

It is also not an immunotherapy biomarker. Checkpoint drug (a type of immunotherapy) choices rest on separate tests. Those are chiefly PD-L1 expression and mismatch repair or microsatellite status. NCI notes about 4% of stage IV colorectal tumors are mismatch repair deficient or MSI-high. That is a different 4% from the G12C figure, and a different path.

And it does not promise durability. Resistance develops. The median durations of response above are measured in months, not years.

More on how these results are generated is in biomarker testing and precision medicine and liquid biopsy versus tissue biopsy.

The two drugs are watched differently, and the labels are specific.

For sotorasib, liver tests are checked every 3 weeks for the first 3 months, then monthly. Interstitial lung disease and pneumonitis (lung inflammation) carry a labeled warning. New or worsening breathing symptoms mean the drug is held at once. Call your care team right away if you have new or worse cough or trouble breathing. For emergencies call 911 or go to the ER. Acid-reducing drugs matter too. The label says to avoid proton pump inhibitors and H2 blockers. If an acid reducer cannot be avoided, the label says to take sotorasib 4 hours before or 10 hours after a local antacid. Ask your care team before taking any heartburn medicine.

For adagrasib, liver tests are checked before starting and monthly for 3 months. It carries a QTc prolongation warning, which is a change in the heart's electrical rhythm. So ECG (a heart tracing) and electrolytes, particularly potassium and magnesium, are monitored in people at risk.

Common side effects overlap. With sotorasib alone in lung cancer, reactions at 20% or more were diarrhea, musculoskeletal pain, nausea, fatigue, liver toxicity, and cough. With adagrasib alone, at 25% or more, they were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, liver toxicity, kidney impairment, swelling, breathlessness, and low appetite. Adding an anti-EGFR antibody adds skin toxicity. Rash, dry skin, and mouth sores stand out in the combination data, along with low magnesium.

Both labels warn against strong CYP3A4 inducers, which are certain medicines that speed up how the body clears these drugs. Your care team and pharmacist can check your other medicines. For a wider view of this drug class, see targeted therapy.

• DailyMed — LUMAKRAS (sotorasib) prescribing information
• DailyMed — KRAZATI (adagrasib) prescribing information
• NCI PDQ — Non-Small Cell Lung Cancer Treatment (Health Professional Version)
• NCI PDQ — Colon Cancer Treatment (Health Professional Version)
• NCI — Sotorasib
• NCI — Adagrasib