KRAS G12C Inhibitor Therapy
Sotorasib and adagrasib are daily tablets that lock onto the KRAS G12C mutation. In previously treated lung cancer they kept the disease in check one to two months longer than docetaxel, and in bowel cancer sotorasib with panitumumab shrank tumors in 26 percent of patients.
About This Department
For forty years KRAS was called undruggable. Two tablets now block one of its mutations, G12C.
The genetic report on your tumor lists a KRAS mutation and names the variant, G12C, and a new tablet has been mentioned. Cancers mutate KRAS more than any other gene, and for four decades no drug could touch it. The G12C variant has a weak point the others lack, and since 2021 two tablets, sotorasib and adagrasib, have locked onto it. What they offer needs to be stated plainly. In lung cancer that had already been through chemotherapy and immunotherapy, both tablets beat the standard second chemotherapy, docetaxel, and kept the cancer in check a little longer, by one to two months at the median, with fewer serious side effects for sotorasib. Bowel cancer needs an antibody alongside the tablet. For patients who have run out of standard options these tablets bring a real advance, smaller than the transformations seen with ALK or EGFR drugs. This page explains the test, the two drugs, the trials as they are, the side effects, and how a daily tablet taken at home fits with a short visit to Istanbul.
What G12C means
KRAS G12C Inhibitor Therapy targets one specific fault in one gene. KRAS works as an on-off switch for cell growth. A mutation jams it in the on position, and the cell divides without stopping.
Each mutation takes its name from its position in the protein. G12C means that at position 12, the amino acid glycine has been replaced by cysteine. That cysteine gives the drug its opening. It gives a drug something to grip, and sotorasib and adagrasib bind to it permanently, holding the switch in the off position. Other KRAS mutations, G12D, G12V and the rest, lack that cysteine, and these two drugs do nothing for them.
Who has it
G12C turns up in around 13 percent of non-small cell lung cancers, most of them in people who smoked, in 3 to 4 percent of bowel cancers, and in 1 to 2 percent of pancreatic cancers. It rarely appears alongside EGFR or ALK changes.
Finding the mutation
A test on the tumor, or on the blood
| Test | Sample | Notes |
|---|---|---|
| Next-generation sequencing | Tumor tissue from the biopsy or operation | Reads dozens of genes at once, and finds any other target that would change the plan |
| Liquid biopsy | A blood sample | Useful when tissue is short. A negative result does not rule the mutation out |
| Single-gene KRAS test | Tumor tissue | Faster and cheaper, and misses the other targets. A broad panel is preferred |
Test first, treat second.
Every advanced lung adenocarcinoma should be tested broadly at diagnosis, before any treatment. The review checks that the report names the exact variant, since a result that says only KRAS mutated does not tell you whether these drugs apply.
Sotorasib and adagrasib
Two tablets, the same target, slightly different habits. Neither has been compared directly with the other.
Lung cancer
Two trials against docetaxel
| CodeBreaK 200, Lancet 2023 | KRYSTAL-12, Lancet 2025 | |
|---|---|---|
| Drug | Sotorasib 960 mg once daily | Adagrasib 600 mg twice daily |
| Patients | 345, after platinum chemotherapy and immunotherapy | 453, after platinum chemotherapy and immunotherapy |
| Median time without progression | 5.6 months against 4.5 with docetaxel | 5.5 months against 3.8 with docetaxel |
| Serious side effects, grade 3 or worse | 33 percent against 40 percent | 47 percent against 46 percent |
| Serious treatment-related events | 11 percent against 23 percent | Not separately given in the abstract |
| Most common severe effects | Diarrhea 12 percent, liver enzyme rises 8 and 5 percent | Consistent with earlier reports |
Neither trial looked at a first treatment.
Both trials enrolled patients whose cancer had grown after the two standard first treatments, platinum chemotherapy and immunotherapy. Approval for lung cancer covers that setting today. Trials combining them with immunotherapy or chemotherapy as a first treatment are running.
What the numbers mean
| Option after chemotherapy and immunotherapy | Form | What to weigh |
|---|---|---|
| Sotorasib or adagrasib | Tablets at home | Modest gain in control, fewer infusions, liver and bowel side effects |
| Docetaxel, with or without ramucirumab | Infusion every three weeks | Similar survival, more hair loss and low blood counts |
| A clinical trial | Varies | Newer KRAS drugs and combinations, where the patient qualifies |
Bowel cancer
The tablet alone falls short
Blocking KRAS G12C in bowel cancer makes the cancer cells switch on EGFR, the receptor above KRAS, and the tablet on its own shrinks few tumors. Adding an antibody against EGFR closes that escape route.
Pancreas and other cancers
Pancreatic cancer
Other cancers
Side effects
Diarrhea, nausea and vomiting
Liver
Tiredness
Heart rhythm, with adagrasib
Living on the tablet
The tablets are taken every day at home, for as long as they work. Most patients keep their routine.
Practical points
Sotorasib goes down at the same time each day, and keep stomach acid blockers away from it, since they cut how much is absorbed. Take adagrasib twice a day with food. Tell every doctor who prescribes something new that you are on a KRAS inhibitor, because several common drugs interact with both. Avoid pregnancy during treatment. A missed dose is skipped rather than doubled.
Days in Istanbul
A short visit
| Visit | Days | What happens |
|---|---|---|
| Starting the tablet | 3 to 4 | Consultation, scans if needed, baseline liver tests and ECG, first prescription |
| Molecular testing first | 5 to 10 | Biopsy or blood sample, sequencing, then the consultation |
| Review visit | 2 to 3 | Scans and liver tests every two to three months, if you prefer to return |
These tablets set no limit on flying. Carry them in hand luggage in their original boxes with the prescription.
What a quote contains
The monthly cost of the tablet
No figure appears here. The tablet, priced per month, makes up the largest cost by far, with the consultation, scans, liver tests, ECG and any molecular testing as smaller separate lines. In bowel cancer the panitumumab infusion every two weeks adds its own line.
Coordinator, language, companion
| Item | Detail |
|---|---|
| Coordinator | One person from the first message, on the same WhatsApp number afterwards |
| Language | English, Arabic, French, Russian, Serbian, Romanian and Spanish, with interpreters for other languages |
| Travel | Accommodation near the hospital, airport transfers, the car to each visit |
| Paperwork | An appointment confirmation and invitation letter for a visa ten days or so before travel |
| Daily needs | Halal, vegetarian and diabetic meals, a prayer room, and a female physician where the rota allows |
The interpreter sits in on the first consultation. That hour covers what the tablet can and cannot do, and the liver warning signs.
Follow-up at home
What your oncologist receives
Once you get back home, your oncologist receives the molecular report, the prescription with the dose, the liver test schedule, the ECG plan for adagrasib, and the list of medicines to avoid. Scans every two to three months and liver tests go to the coordinator, and the oncologist here reviews them at no charge.
KRAS G12C Inhibitor Therapy FAQ
What is a KRAS G12C mutation?
Which drugs target KRAS G12C?
How well do they work in lung cancer?
Do they work in bowel cancer?
What are the main side effects?
How long do I need to stay in Istanbul?
Will the staff be able to speak my language?
References
- de Langen AJ, Johnson ML, Mazieres J, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS G12C mutation: a randomised, open-label, phase 3 trial. The Lancet. 2023;401(10378):733-746.
- Barlesi F, Yao W, Duruisseaux M, et al. Adagrasib versus docetaxel in KRAS G12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. The Lancet. 2025;406(10503):615-626.
- Fakih MG, Salvatore L, Esaki T, et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. The New England Journal of Medicine. 2023;389(23):2125-2139.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Metin GÜDEN, Radiation Oncology.
Medically reviewed by
Prof. Dr. Metin GÜDEN
Radiation Oncology
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