Divarasib helped patients live longer and kept the cancer under control for longer.

“For decades, we haven’t been able to design targeted drugs against cancers specifically targeting the KRAS mutation,” said Dr. Pasi A. Jänne, a lung cancer specialist and senior vice president for translational medicine at Dana-Farber Cancer Institute.

He described this newer generation of KRAS drugs as a major change for patients who previously had few targeted options.

What Is KRAS G12C?

KRAS is a gene that helps tell cells when to grow and when to stop. A mutation is an abnormal change in that gene.

With KRAS G12C, the growth signal can become stuck in the “on” position. This allows cancer cells to keep growing.

The mutation is found in approximately one out of every eight people with non-small cell lung cancer. It is usually found only in the cancer cells and is not something a patient inherited or passed to their children.

Doctors can look for KRAS G12C through biomarker testing. This may involve testing tissue collected during a biopsy or looking for tumor DNA in a blood sample.

What Did the Study Find?

KRASCENDO-1 included 338 people with advanced KRAS G12C-positive lung cancer that had progressed after previous treatment.

Patients received either divarasib or one of the currently available pills, sotorasib or adagrasib.

One key measure was progression-free survival, the amount of time a person lives without the cancer growing or spreading. The cancer remained controlled for a median of 9.8 months with divarasib, compared with 5.7 months with the current drugs.

Patients receiving divarasib also lived longer overall. Median survival was 17.7 months with divarasib and 12 months with sotorasib or adagrasib.

At one year:

• 67.1% of patients taking divarasib were alive.
• 49.2% of patients taking sotorasib or adagrasib were alive.

Tumors shrank in 58.4% of patients receiving divarasib, compared with 32.3% receiving one of the current pills.

These results do not predict exactly what will happen to one person. Some patients live for less time than the median, while others live much longer. Still, the study offers real hope that a more effective targeted treatment may soon become available.

What Could Change for Patients?

Divarasib is not yet FDA-approved.

If it is approved, it may become the preferred KRAS G12C pill for patients whose cancer has progressed after initial treatment. Dr. Jänne said the stronger cancer control, longer survival, and lower rate of severe side effects mean it “will likely be the new standard of care” in this setting.

For patients, this could mean another chemotherapy-free treatment option. Divarasib is taken by mouth once a day.

However, the study mostly compared divarasib with sotorasib. Only a small number of patients received adagrasib, so the comparison with adagrasib is less certain.

The trial also did not include people who had already taken a KRAS G12C inhibitor. It therefore does not tell us whether switching to divarasib will help after sotorasib or adagrasib has stopped working.

What About Side Effects?

Severe (grade 3 or higher) treatment-related side effects occurred in about 25% of patients taking divarasib and 35% receiving the current drugs.

Fewer patients stopped treatment because of side effects with divarasib: about 5%, compared with 12%.

Divarasib did cause more diarrhea, nausea and vomiting, but these problems were usually mild. Liver-related side effects were less common with divarasib than with sotorasib or adagrasib.

Dr. Jänne said fewer severe side effects may mean fewer emergency room visits and hospital stays. That can make a meaningful difference in daily life.

Patients should tell their care team about diarrhea or nausea early. These symptoms can often be controlled with medication, diet changes, or a temporary treatment adjustment.

Why Biomarker Testing Matters

A targeted drug cannot be considered unless doctors know that the tumor carries KRAS G12C.

“Everyone should be getting biomarker testing,” Dr. Jänne said.

Broad biomarker testing can find KRAS G12C and other mutations that may guide treatment. Ideally, it should be performed when advanced lung cancer is diagnosed, rather than waiting until the first treatment stops working.

The hopeful message from KRASCENDO-1 is not only that another drug is coming. It is that researchers are learning how to make targeted treatments work better, last longer, and help patients live longer.

Questions To Ask Your Doctor

• Has my cancer been tested for KRAS G12C?
• Did I receive broad biomarker testing, such as next-generation sequencing?
• Where would divarasib fit into my treatment plan?
• Is divarasib FDA-approved or available through a clinical trial?
• What side effects should I expect?
• If I already took sotorasib or adagrasib, is there evidence that divarasib could help me?

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