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
Medical Oncology
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.
5.6 vs 4.5 mo
Time without progression, sotorasib against docetaxel, lung cancer, CodeBreaK 200
5.5 vs 3.8 mo
Time without progression, adagrasib against docetaxel, KRYSTAL-12
26.4% vs 0%
Tumor shrinkage in bowel cancer, sotorasib with panitumumab against standard care
Free
Review of your molecular report and treatment history
Free consultation
The review of your file is free and commits you to nothing. Send the molecular report naming the KRAS variant, the pathology report, recent scans, every treatment so far with dates, and your current medicines. A medical oncologist tells you whether a G12C inhibitor fits now, which one, whether a clinical trial would serve you better, and what else the report might open up, and a coordinator writes to you in your own language.
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
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Tests that find KRAS G12C
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.
How they are taken
Sotorasib, sold as Lumakras or Lumykras, is taken as 960 milligrams once a day, eight tablets together. Adagrasib, sold as Krazati, is taken as 600 milligrams twice a day, three tablets each time. Adagrasib reaches the brain somewhat better in early studies, and it can lengthen the heart rhythm interval on an ECG, which matters for patients on other drugs that do the same. Sotorasib is absorbed poorly alongside stomach acid blockers, and those are avoided or timed apart.
Lung cancer
Two trials against docetaxel
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KRAS G12C inhibitors in previously treated lung cancer
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
A modest gain, stated plainly
At the median, sotorasib added about one month and adagrasib about one and a half months before the cancer grew, compared with docetaxel. Neither abstract reports longer overall survival. What the tablets offer is similar or better control with a tablet at home in place of an infusion every three weeks, and, for sotorasib, fewer serious side effects. For many patients that trade is worth making. It should be made knowing its size.
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Where the tablets stand
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.
CodeBreaK 300, New England Journal of Medicine 2023
160 patients with G12C bowel cancer that had outlasted standard chemotherapy received sotorasib 960 mg with panitumumab, sotorasib 240 mg with panitumumab, or trifluridine-tipiracil or regorafenib. Median time without progression was 5.6 months at the full dose against 2.2 months on standard care, and tumors shrank in 26.4 percent against 0 percent. Serious side effects occurred in 35.8 percent against 43.1 percent, mostly skin rash and low magnesium from the antibody. Survival data were still maturing.
Pancreas and other cancers
Pancreatic cancer
G12C accounts for 1 to 2 percent of pancreatic cancers. Early studies show tumor shrinkage in some patients, and a tablet may be offered where standard treatment has stopped working, often within a trial.
Other cancers
Appendix, bile duct, uterine and other cancers occasionally carry G12C. Treatment is decided case by case on the strength of small studies.
Other KRAS mutations
G12D, the most common KRAS variant in pancreatic and bowel cancer, and the others are the target of newer drugs now in trials, including ones that act on many KRAS variants at once. A report with a non-G12C KRAS mutation deserves a review for trial options.
Side effects
Diarrhea, nausea and vomiting
The commonest effects. Taking the tablets with food helps with adagrasib, and anti-diarrhea and anti-sickness medicines cover most cases.
Liver
Rises in liver enzymes, sometimes severe. The risk is higher in patients who received immunotherapy within the previous few months. Liver tests every three weeks for the first three months, then monthly, catch it early, and a pause and lower dose usually settle it.
Tiredness
Common, and usually mild.
Heart rhythm, with adagrasib
A lengthening of the QT interval on the ECG. An ECG before starting and after, and a check of other medicines that do the same.
The immunotherapy interval
Most patients reach these tablets straight after immunotherapy. Immune drugs linger in the body for months, liver inflammation runs higher in that window, and so the oncologist watches the liver tests more closely in the first weeks than at any later point in treatment.
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
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Time in Istanbul
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.
Before comparing
Packages published by Turkish hospitals and medical travel agencies for targeted therapy cover the consultation, scans and a first prescription, and leave out months of the drug, flights and accommodation. A quote you can compare names the drug, the number of months, and whether testing is inside the figure. Ask whether your insurer at home pays for the tablet once prescribed. It follows the free review.
Coordinator, language, companion
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What the international patients office arranges
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.
Same day, local doctor
Yellowing of the skin or eyes, dark urine, severe or bloody diarrhea, fainting or palpitations on adagrasib, or new breathlessness.
KRAS G12C Inhibitor Therapy FAQ
What is a KRAS G12C mutation?
A change in the KRAS gene at position 12, where glycine is replaced by cysteine. It keeps the cell growth switch permanently on. It is found in around 13 percent of non-small cell lung cancers and 3 to 4 percent of bowel cancers.
Which drugs target KRAS G12C?
Sotorasib, taken once a day, and adagrasib, taken twice a day. Both bind the mutant protein permanently.
How well do they work in lung cancer?
After chemotherapy and immunotherapy, median time without progression was 5.6 months with sotorasib against 4.5 with docetaxel, and 5.5 months with adagrasib against 3.8. The gain is modest.
Do they work in bowel cancer?
With an antibody, yes. In CodeBreaK 300, sotorasib with panitumumab shrank tumors in 26.4 percent of patients and gave 5.6 months without progression against 2.2 on standard care.
What are the main side effects?
Diarrhea, nausea and rises in liver enzymes, with heart rhythm changes on the ECG for adagrasib, which is why liver tests are checked every three weeks in the first three months.
How long do I need to stay in Istanbul?
Three to four days to start the tablet, covering the consultation, baseline liver tests and ECG, and the first prescription. After that it is taken at home, and scans are reviewed from there.
Will the staff be able to speak my language?
The international patients team works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and arranges interpreters for other languages.
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. Mustafa Teoman YANMAZ, Medical Oncology.
