Treating solid tumors with KRAS G12C mutation by using Divarasib
|
Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on September 18th, 2023
|
Previous studies had shown that 12% of non-small-cell lung cancer (NSCLC) and 4% of colorectal cancer cases possess a glycine-to-cysteine mutation at the 12th amino acid of the KRAS protein. These cases of cancer are frequently treated with anti-tumor agents like Sotorasib and Adagrasib; however, their efficacy is suboptimal. Thus, amore potent KRAS G12C inhibitor is needed. Recently, a study published their findings on the effectiveness and safety of Divarasib in the New England Journal of Medicine.
Divarasib was developed by Genentech, and previous in vitro studies had shown that its potency was 20 times greater than Sotorasib and 50 times greater than Adagrasib. Thus, a subsequent phase 1 clinical trial was conducted with 137 patients who had been diagnosed with metastatic solid tumors with KRAS G12C mutation. To determine the best working and safest dosage, the patients were randomly assigned to receive 4 different dose levels of Divarasib orally - 40 mg, 100 mg, 200 mg, and 400 mg - once a day, every 21 days. This cycle continued until the patients withdrew from the study or their disease progressed. The median treatment time was 6.9 months, and the researchers discovered that Divarasib helped reduce the size of colorectal and NSCLC tumors in 29.1% and 53.4% of the patients, respectively. Though imperfect, cross-study comparison showed that the partial response rate of Divarasib is higher than Sotorasib. Divarasib suppressed the tumor growth; the median progression-free survival duration was 13.1 months for the NSCLC group and 5.6 months in the colorectal cancer patients. Despite the high dosage, the researchers did not detect any significant change in toxicity as the dose was increased. Most of the adverse effects were mild to moderate; only 12% of the reported events were serious. However, little can be concluded from this result, because there was not a control group who were treated with either placebo or another regimen.
Divarasib was developed by Genentech, and previous in vitro studies had shown that its potency was 20 times greater than Sotorasib and 50 times greater than Adagrasib. Thus, a subsequent phase 1 clinical trial was conducted with 137 patients who had been diagnosed with metastatic solid tumors with KRAS G12C mutation. To determine the best working and safest dosage, the patients were randomly assigned to receive 4 different dose levels of Divarasib orally - 40 mg, 100 mg, 200 mg, and 400 mg - once a day, every 21 days. This cycle continued until the patients withdrew from the study or their disease progressed. The median treatment time was 6.9 months, and the researchers discovered that Divarasib helped reduce the size of colorectal and NSCLC tumors in 29.1% and 53.4% of the patients, respectively. Though imperfect, cross-study comparison showed that the partial response rate of Divarasib is higher than Sotorasib. Divarasib suppressed the tumor growth; the median progression-free survival duration was 13.1 months for the NSCLC group and 5.6 months in the colorectal cancer patients. Despite the high dosage, the researchers did not detect any significant change in toxicity as the dose was increased. Most of the adverse effects were mild to moderate; only 12% of the reported events were serious. However, little can be concluded from this result, because there was not a control group who were treated with either placebo or another regimen.