What You Should Know
- An experimental drug called divarasib helped people with KRAS G12C-mutated lung cancer live longer and go longer without their cancer growing compared with the two currently approved KRAS-targeted treatments.
- More patients saw their tumors shrink with divarasib during a clinical trial, and those responses lasted longer.
- “It also had fewer side effects,” says Dr. Jia Luo, a lung cancer specialist at Dana-Farber Cancer Institute. Serious side effects and treatment discontinuations were less common with divarasib, though stomach-related side effects such as diarrhea, nausea, and vomiting were more common and mostly mild.
- Divarasib is not yet FDA-approved, so it is mainly available through clinical trials. Ask your doctor whether you may be eligible.
If you have non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, there may be a new option on the horizon. This genetic change, found in about 1 in 8 people with the most common type of lung cancer, can cause cancer cells to grow out of control. In the phase 3 Krascendo 1 study, divarasib led to significantly longer progression-free and overall survival than current treatment in people whose cancer had already been treated.
Read MoreWhat Is KRAS G12C?
KRAS is a gene that helps tell cells when to grow and when to stop. With the G12C mutation, that growth signal can get stuck in the “on” position, allowing cancer cells to keep growing. The G12C mutation is found in “roughly 12% of mutations in non-squamous NSCLC,” according to the American Journal of Managed Care.Your doctor can check for it with biomarker testing, using a tissue sample from a biopsy or a blood test.
What the Study Found
The phase 3 Krascendo 1 clinical trial included 338 adults. They were randomly assigned to take divarasib once a day, or one of the two KRAS G12C pills already in use, sotorasib (Lumakras) or adagrasib (Krazati).
Typically, cancer was held back (also referred to as median progression-free survival, or PFS) for 9.8 months with divarasib, compared with 5.7 months with the current pills. That’s a 42% lower risk of the cancer growing or the patient dying.
Half of patients taking divarasib lived at least 17.7 months (median overall survival), compared with 12.0 months with the current treatment. That’s a 44% lower risk of death.
Patients were nearly twice as likely to respond to divarasib (58.4% vs. 32.3% overall response rate), and responses lasted longer.
Dr. Luo says the gains were a little more than four extra months before the cancer grew, and more than five extra months of life, on average.
What About Side Effects?
“It also had fewer side effects,” Dr. Luo says.
Overall, the data back that up. Serious side effects were about half as common with divarasib (7.8% vs. 15.2%), and fewer people had to stop treatment because of side effects (4.8% vs. 11.7%).
Liver problems were also less common. None of the patients in the clinical trial who took divarasib developed treatment-related lung inflammation (pneumonitis), compared with three patients taking the current pills.
Dr. Luo noted that pneumonitis is “a rare side effect but can be very serious.”
Stomach-related side effects are the main trade-off. Diarrhea, nausea, and vomiting were more common with divarasib, though they were mostly mild.
Experts at ESMO also noted that the clinical trial didn’t report how long these side effects lasted, which matters for daily life.
“So overall, the medicine seems to be better at controlling the cancer, helping patients live longer, but also having fewer side effects,” Dr. Luo says.
Helpful Resources for Lung Cancer Patients
Can I Get Divarasib Now?
Divarasib is not yet approved by the Food and Drug Administration (FDA), so it is mainly available through clinical trials. The FDA has granted it Breakthrough Therapy Designation (2022) and Orphan Drug Designation (2026) for KRAS G12C-mutated NSCLC.
What the Krascendo 1 Study Doesn’t Answer Yet
- How divarasib compares with each current KRAS-targeted drug. Most patients in the comparison group received sotorasib, while far fewer received adagrasib. As a result, the study provides a clearer picture of how divarasib stacks up against sotorasib than against adagrasib.
- How long side effects may affect daily life. While divarasib was linked to more stomach-related side effects, such as diarrhea, nausea, and vomiting, researchers did not report how long these symptoms lasted. That information could be important for patients considering treatment over many months.
- The study was not blinded. Patients and their doctors knew which treatment they were receiving. However, the trial’s main measure of effectiveness, how long patients lived before their cancer grew or spread, was reviewed independently to help reduce bias.
Questions to Ask Your Doctor
- Has my tumor been tested for KRAS G12C and other biomarkers?
- If my current treatment stops working, what are my options?
- Am I eligible for a clinical trial of divarasib or other new KRAS treatments?
- What side effects should I watch for, and how can we manage stomach-related ones?
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