Sotorasib can improve progression-free survival (PFS), compared with docetaxel, in patients with previously treated KRASG12C-mutated non-small cell lung cancer (NSCLC), according to results from the phase 3 CodeBreak 200 trial presented at ESMO Congress 2022.

Researchers found that sotorasib reduced the risk of progression or death by 34%. There was no significant difference in overall survival (OS) between the treatment arms, but the study was underpowered for OS.

Taken together, these results support sotorasib as a new second-line standard in this patient population, according to study presenter Melissa L. Johnson, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee.

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The CodeBreak 200 trial ( Identifier: NCT04303780) included 345 patients with metastatic or unresectable locally advanced KRASG12C-mutated NSCLC who had disease progression after platinum-based chemotherapy and immune checkpoint inhibitor treatment. 

The patients were randomly assigned to sotorasib (n=171) or docetaxel (n=174). Oral sotorasib was given at a dose of 960 mg daily. Intravenous docetaxel was given at 75 mg/m2 every 3 weeks. 

Crossover was allowed from the docetaxel arm to the sotorasib arm; 26.4% of patients crossed over per protocol, and 7.5% received subsequent treatment with a KRASG12C inhibitor. The proportion of patients who received any treatment after study treatment, including crossover, was 36% in the sotorasib arm and 42% in the docetaxel arm.

The study’s primary endpoint was PFS by blinded independent central review. At a median follow-up of 17.7 months, the primary endpoint was met. 

The median PFS was 5.6 months in the sotorasib arm and 4.5 months in the docetaxel arm (hazard ratio, 0.66; 95% CI, 0.51-0.86; P =.002). The 12-month PFS rates were 24.8% and 10.1%, respectively. 

The overall response rate was 28.1% in the sotorasib arm and 13.2% in the docetaxel arm (P <.001). The disease control rates were 82.5% and 60.3%, respectively. The median duration of response was 8.6 months and 6.8 months, respectively.

Dr Johnson noted that overall survival (OS) was similar between the treatment arms, but the study was underpowered for OS. The median OS was 10.6 months in the sotorasib arm and 11.3 months in the docetaxel arm (hazard ratio, 1.01; 95% CI, 0.77-1.33; P =.53). 

The safety analysis included 169 patients in the sotorasib arm and 151 patients in the docetaxel arm. Treatment-related adverse events (TRAEs) of any grade were reported in 70.4% of patients in the sotorasib arm and in 86.1% of those in the docetaxel arm. 

Grade 3 or higher TRAEs occurred in 33.1% of patients in the sotorasib arm and 40.4% of those in the docetaxel arm. Serious TRAEs were reported in 10.7% and 22.5%, respectively. Discontinuation due to TRAEs was reported in 9.5% and 11.3%, respectively.

There was 1 fatal TRAE in the sotorasib arm (due to interstitial lung disease), and there were 2 fatal TRAEs in the docetaxel arm (due to ileus and multiorgan failure).

Disclosures: This research was supported by Amgen. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Johnson ML, de Langen J, Waterhouse DM, et al. Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study. Presented at ESMO 2022; September 9-13, 2022. Abstract LBA10.