Grok, tell me all about sotorasib in lung cancer.
– Sotorasib is a targeted therapy for non-small cell lung cancer (NSCLC) with a specific mutation in the KRAS gene known as G12C. This mutation is found in about 13% of NSCLC cases and is associated with smoking.
Sotorasib works by binding to the mutated KRAS protein, preventing it from sending signals that promote cancer growth. It was approved by the FDA in May 2021 as the first targeted therapy for NSCLC with the KRAS G12C mutation, after showing promising results in clinical trials.
In the CodeBreaK 100 trial, sotorasib was given to 126 patients with advanced NSCLC and the KRAS G12C mutation. The overall response rate was 36%, with 46 patients (37.1%) having a partial or complete response to the treatment. The median duration of response was 10 months.
Common side effects of sotorasib include diarrhea, fatigue, nausea, and liver enzyme elevations. However, most side effects were manageable and reversible.
Sotorasib represents a significant advancement in the treatment of NSCLC with the KRAS G12C mutation, offering a targeted therapy option for patients who have received prior treatments. It is administered orally once daily and has been shown to shrink tumors and improve survival outcomes in clinical trials.
Discuss the Codebreak trial.
– The CodeBreaK 100 trial was a phase 2 study that evaluated the efficacy and safety of sotorasib (Lumakras) in patients with advanced non-small cell lung cancer (NSCLC) who had a specific mutation in the KRAS gene known as G12C. The trial enrolled 126 patients with advanced NSCLC and the KRAS G12C mutation, and all had received prior treatments.
The overall response rate was 36.3%, with 46 patients (37.1%) having a partial or complete response to the treatment. The median duration of response was 10 months. The median overall survival was 12.5 months, with 51% of patients still alive after 1 year and 33% still alive after 2 years.
Common side effects of sotorasib included diarrhea, fatigue, nausea, and liver enzyme elevations. However, most side effects were manageable and reversible.
The CodeBreaK 100 trial demonstrated that sotorasib is an effective and safe treatment option for patients with advanced NSCLC and the KRAS G12C mutation who have received prior treatments. It was the first targeted therapy approved for this specific patient population.
And the Codebreak 200 trial?
– The CodeBreaK 200 trial was a phase 3 study that evaluated the efficacy and safety of sotorasib (Lumakras) in patients with advanced non-small cell lung cancer (NSCLC) who had a specific mutation in the KRAS gene known as G12C. The trial enrolled 345 patients with advanced NSCLC and the KRAS G12C mutation, and all had received prior treatments.
The primary analysis of the CodeBreaK 200 trial showed that sotorasib significantly increased progression-free survival compared with docetaxel, with a 34% reduction in the relative risk of having disease progression or death. The median progression-free survival was 5.6 months with sotorasib vs 4.5 months with docetaxel.
The overall response rate was also significantly higher with sotorasib compared with docetaxel. The most common treatment-related adverse events with sotorasib were diarrhea, increased alanine aminotransferase, and increased aspartate aminotransferase.
The CodeBreaK 200 trial demonstrated that sotorasib is an effective and safe treatment option for patients with advanced NSCLC and the KRAS G12C mutation who have received prior treatments. It was the first randomized phase 3 trial for a KRAS G12C inhibitor, and the results support the use of sotorasib as a standard of care for this patient population.
What was the difference in overall survival?
– According to the CodeBreaK 200 trial results, the median overall survival was 10.6 months with sotorasib vs 11.3 months with docetaxel, an almost 1-month absolute difference that was not statistically significant.
So, sotorasib was not better than docetaxel right?
– That’s correct. The CodeBreaK 200 trial showed that sotorasib did not significantly improve overall survival compared to docetaxel in patients with KRAS G12C-mutated NSCLC. The median overall survival was 10.6 months with sotorasib vs 11.3 months with docetaxel.