Sotorasib is the first targeted therapy for patients with non–small cell lung cancer (NSCLC) whose tumors express a KRAS G12C mutation and who have received at least 1 prior therapy for their disease.
Sotorasib, is an anti-cancer medication used to treat non-small-cell lung cancer, and targets a specific mutation, G12C, in the protein K-Ras encoded by gene KRAS which is responsible for various forms of cancer.
Sotorasib is an inhibitor of the RAS GTPase family.
The KRAS G12C mutation occurs in codon 12 and results in the substitution of a glycine with cysteine.
The KRAS G12C mutation is induced by smoking and is responsible for about 12% of lung adenocarcinomas..
Lumakras trade name.
Pregnancy category AU: B3
Routes of administration By mouth
Phase 1/2 CodeBreaK 100 clinical trial demonstrated the agent’s ability to induce deep and durable responses in the indicated patient population.
In 124 evaluable patients with locally advanced or metastatic disease progressing after an immune checkpoint inhibitor and/or platinum-based chemotherapy, the objective response rate with sotorasib was 36% with 56% of patients maintaining a response longer than 6 months.
Patients achieving complete and partial responses or stable disease–was 81%.
The most common adverse effects: diarrhea, musculoskeletal pain, nausea, fatigue, liver damage and cough.
KRAS mutation accounts for approximately 25% of mutations in non-small cell lung cancers.
KRAS G12C mutations occur in about 13% of patients with non-small cell lung cancers.
Considered to be a first-in-class medication.
Sotorasib is indicated for the treatment of adults with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer.
The G12C KRAS mutation is relatively common in some cancer types, 14% of non-small-cell lung cancer adenocarcinoma patients and 5% of colorectal cancer patients.
In a randomized phase 3 trial, sotorasib was compared with docetaxel in 345 patients with KRAS G12C-mutated non-small-cell lung cancer (NSCLC) previously treated with previous platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor: improvement in the progression-free survival for sotorasib (960 mg daily), compared with docetaxel (median progression-free survival 5.6 months vs 4.5 months.
The radiographic response rate for sotorasib was 28.1% compared with 13.2% response rate for docetaxel.
Overall survival was not different between sotorasib and docetaxel.
At its introduction, in the United States, Sotorasib costs US$17,900 per month.
Recommended dosage is 960 mg a day/8 120 mg tablets orally once daily.
Drug absorption is reduced by administration of gastric acid, reducing agents.
Coadministration with strong CYP3A4 inducer decreases concentrations and administration of a P glycoprotein substrate may increase adverse reactions.