New breakthrough in targeted treatment of KRAS mutated lung cancer: detailed analysis of Adagrasib efficacy, price and drug purchase guide

1. Hot topic introduction:KRASThe mutation is no longer "incurable", and adagrasib is once again in the global spotlight

2024At the end of 2024, "The Lancet Oncology" announced the latest KRYSTAL series of research results, showing that KRAS Patients with G12Cmutations have achieved remarkable results after using Adagrasib (Adagrasib) - this news quickly became a hot topic in the global oncology community.

As the world's second KRAS G12C targeted drug after sotorasibu, the emergence of adagrasiib is considered a "key milestone in precision medicine." KRASMutations have long been regarded as an "undruggable" problem, but now, this "forbidden zone" has been completely broken.

The efficacy data of adagrasib has refreshed people's understanding of KRAS targets, and has also rekindled hope for many patients with advanced non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer.

2. Drug overview: What is adagrasib?

Adagrasib (Adagrasib, trade name Krazati) was developed by the American biopharmaceutical company Mirati Therapeutics and is a highly selective, irreversible KRAS G12C inhibitor.

Its mechanism of action is to covalently bind KRAS G12C mutant protein and fix it in an inactivated state, thus blocking the key pathways in the signal transduction chain (RAS/RAF/MEK/ERK) to achieve the purpose of inhibiting tumor cell proliferation.

Adagrasiib has a longer half-life (approximately23 hours), can maintain a more stable blood concentration, and shows better central nervous system (CNS) penetration in patients with brain metastases, so it is clinically considered to be a representative drug of the second generation KRAS inhibitors.

3. KRYSTALResearch data: The efficacy of adagrasib is impressive

Based on international multi-center clinical trial KRYSTAL-1Research results:

Among previously treated KRAS G12C mutated patients with advanced NSCLC, the objective response rate (ORR) was 43%;

The disease control rate (DCR) is as high as 80% or more;

The median progression-free survival (PFS) is about6.5 months;

In patients with brain metastases, the intracranial response rate reaches 33%, which is significantly better than traditional chemotherapy.

Follow-up KRYSTAL-12 III The phase clinical trial showed that compared with docetaxel, adagrasib significantly prolonged patient survival time and had milder side effects.

It is worth noting that in some patients with colorectal cancer (CRC), adagrasib combined with EGFR inhibitors (such as cetuximab) has shown good efficacy, bringing new ideas to the treatment of KRAS mutant colorectal cancer.

4. Indications and Medication Guide

1.Adaglasib has been approved by the United StatesFDAApproved for the following patients:

Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who carryKRAS G12C mutations and need to use it after failure of previous standard treatments;

Also used to treat adult patients with KRAS G12C mutated locally advanced or metastatic colorectal cancer. .

2.Medicine administration method

The recommended dose is 600mg, taken orally twice daily;

Can be taken with food or after mealsWithin 30 minutes;

If serious adverse reactions occur, the dose can be adjusted to 400mg or 300mg under the guidance of a doctor, twice a day;

If patients are taking CYP3A4 metabolizing drugs at the same time, special attention should be paid to drug interactions.

3.Notes

Avoid using it with strong inducers (such as rifampicin) to avoid reducing the efficacy of the drug;

It is recommended to monitor liver function and electrocardiogram monthly;

It should be used with caution for pregnant women, lactating mothers and those with liver and kidney dysfunction.

5. Real clinical feedback: stable efficacy and mild side effects

In real-world clinical feedback, the treatment experience with adagrasib was deemed“stable and controllable”:

1.About 60% of patients have significant improvement in symptoms within 4 weeks, such as relief of dyspnea, cough, and chest tightness;

2.Reexamination of imaging in some patients showed tumor shrinkage30%—50%;

3.The ability to control brain metastases is particularly outstanding.

4.Common adverse reactions include:

Mild diarrhea, nausea and vomiting (within 30%);

Mild to moderate elevations in liver enzymes;

Some patients experience fatigue or loss of appetite.

5.Clinicians generally believe that:

"Adagrasiib has a high safety profile, controllable side effects, and is suitable for long-term oral maintenance treatment."

6. Price information: The original drug is expensive, but the Laos generic version is more cost-effective

At present, adagrasib is not yet available in mainland China, and patients need to purchase it through overseas channels.

The price of the original drug in the United States: approximately 1010,000 yuan to 1510,000 yuan/ box (slightly fluctuating depending on specifications);

Prices of generic drugs in Laos: The generic version jointly produced by Lucius (Lucius) and Bear Pharma (Bear Pharma) costs about 3,000 RMB per box;

The ingredients of generic drugs are basically the same as those of the original drugs, and the active ingredients are Adagrasib.

Due to the huge price disparity, many patients will choose to purchase generic drugs through legal cross-border drug service channels under the guidance of doctors to achieve long-term medication affordability.

VII. Domestic listing and medical insurance prospects

Adagrasib's domestic marketing approval is under accelerated review by the National Medical Products Administration (NMPA).

In view of my country's positive attitude towards medical insurance negotiations for innovative targeted drugs, once adagrasib is launched, it is very likely to be included in the national medical insurance directory within two years.

This will mean——KRAS G12C mutation patients will shift from “high-priced out-of-pocket” to “accessible to medical insurance” to achieve sustainable treatment.

8. Patient medication recommendations and drug purchase channels

While it has not yet been approved in the country, if patients need to use adagrasib, they may consider the following paths:

1.Participate in international multi-center clinical trials;

2.Purchase generic drugs through formal cross-border pharmaceutical service platforms;

3.Evaluate the efficacy and risks under the guidance of the attending physician, and conduct periodic monitoring.

4. When purchasing medicines, be sure to verify the legality of the source of the medicines and avoid purchasing from personal agents or unqualified channels to prevent the purchase of counterfeit medicines.

The emergence of adagrasib symbolizes an "irreversible breakthrough" in KRAS mutation treatment. It makes previously "untargetable" cancers treatable again, giving more patients the opportunity to obtain high-quality, long-term life extension. Although high prices are still a real challenge, the emergence of generic drugs in Laos and other places is gradually making targeted treatments "within reach." In the near future, with the acceleration of policies and medical insurance coverage, adagrasib is expected to truly enter the treatment plan of more Chinese patients. "The significance of adagrasib is not only the launch of a drug, but also a step towards popularization of precision cancer treatment."

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References

1.Jänne PA et al. Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation. N Engl J Med. 2022;387:120–131.

2.FDA Official Drug Approval Document – https://www.fda.gov

3.ESMO 2024 Annual Report – KRYSTAL-1/12 Study Update

4.NCCN Guidelines 2025 – KRAS G12C Mutation Targeted Therapy