CodeBreaK 200 Trial: Sotorasib vs Docetaxel in Previously Treated Patients With Advanced KRAS G12C–Mutated NSCLC

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As reported in The Lancet by de Langen et al, the phase III CodeBreaK 200 trial has shown a significant improvement in progression-free survival with sotorasib vs docetaxel in previously treated patients with advanced KRAS G12C–mutated non–small cell lung cancer (NSCLC).

Study Details

In the open-label trial, 345 patients from sites in 22 countries with disease progression after platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor were randomly assigned between June 2020 and April 2021 to receive sotorasib at 960 mg once daily (n = 171) or docetaxel at 75 mg/m² every 3 weeks (n = 174), with treatment continued until disease progression or unacceptable toxicity. Crossover from docetaxel to sotorasib was allowed after confirmed radiologic progression. The primary endpoint was progression-free survival on blinded independent central review in the intention-to-treat population.

Progression-Free Survival

Median follow-up was 17.7 months (interquartile range = 16.4–20.1 months). Median progression-free survival was 5.6 months (95% confidence interval [CI] = 4.3–7.8 months) in the sotorasib group vs 4.5 months (95% CI = 3.0–5.7 months) in the docetaxel group (hazard ratio [HR] = 0.66, 95% CI = 0.51–0.86, P = .0017). Progression-free survival rates at 12 months were 24.8% vs 10.1%.  

Objective response rates were 28.1% (95% CI = 21.5%–35.4%) vs 13.2% (95% CI = 8.6%–19.2%, P < .001), and disease control rates were 82.5% vs 60.3%. Median response durations were 8.6 months (95% CI = 7.1–18.0 months) vs 6.8 months (95% CI = 4.3–8.3 months).

Subsequent therapy was received by 36% of patients in the sotorasib group and 42% of patients in the docetaxel group. A total of 34% of those in the docetaxel group received a KRAS G12C inhibitor, including 26% who crossed over to receive sotorasib. Median overall survival was 10.6 months (95% CI = 8.9–14.0 months) in the sotorasib group vs 11.3 months (95% CI = 9.0–14.9 months) in the docetaxel group (HR = 1.01, 95% CI = 0.77–1.33, P = .53).

Adverse Events

Treatment-related grade ≥ 3 adverse events occurred in 33% of patients in the sotorasib group vs 40% of the docetaxel group; the most common were diarrhea (12%), increased alanine aminotransferase (8%), and increased aspartate aminotransferase (5%) with sotorasib, and neutropenia (9%), fatigue (6%), and febrile neutropenia (5%) with docetaxel. Serious treatment-related adverse events occurred in 11% vs 23% of patients. Treatment-related adverse events led to discontinuation of treatment in 10% vs 11% of patients. Fatal treatment-related adverse events occurred in one patient in the sotorasib group (interstitial lung disease) and in two patients in the docetaxel group (ileus and multiorgan failure).

The investigators concluded, “Sotorasib significantly increased progression-free survival and had a more favorable safety profile compared with docetaxel in patients with advanced NSCLC with the KRAS G12C mutation and who had been previously treated with other anticancer drugs.”

Luis Paz-Ares, MD, PhD, of the Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Amgen. For full disclosures of the study authors, visit

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