# Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS G12C mutation: a randomised, open-label, phase 3 trial

Source: https://onco.cc/key-papers/paper-de-langen-codebreak-200-sotorasib-docetaxel-lancet-2023/  
OnCo record `paper-de-langen-codebreak-200-sotorasib-docetaxel-lancet-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first randomised test of a KRAS inhibitor. Sotorasib beat docetaxel on time to progression by about a month, with fewer serious side effects. A real but modest win against the commonest driver in lung cancer.

## Summary

The CodeBreaK 200 investigators, reported by de Langen, Johnson, Mazieres and colleagues, randomised 345 patients with KRAS G12C-mutated advanced non-small-cell lung cancer who had progressed after platinum chemotherapy and a PD-1 or PD-L1 inhibitor to oral sotorasib 960 mg daily (171) or intravenous docetaxel 75 mg per square metre every three weeks (174), across 148 centres in 22 countries.

KRAS was undruggable for thirty years, and the G12C covalent inhibitors are the proof that it is not. Set against that, CodeBreaK 200's 1.1-month gain in median progression-free survival, with no overall survival benefit, is a sober reminder that hitting a target is not the same as controlling a disease.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: The Lancet
- Year: 2023
- DOI: 10.1016/S0140-6736(23)00221-0
- Authors: de Langen AJ, Johnson ML, Mazieres J, et al.
- Findings: Median progression-free survival 5.6 months (95 percent confidence interval 4.3 to 7.8) with sotorasib against 4.5 months (3.0 to 5.7) with docetaxel: hazard ratio 0.66 (0.51 to 0.86; P equals 0.0017), after a median follow-up of 17.7 months.; Grade 3 or worse treatment-related adverse events in 56 of 169 treated patients (33 percent) on sotorasib against 61 of 151 (40 percent) on docetaxel.; Serious treatment-related adverse events in 18 patients (11 percent) on sotorasib against 34 (23 percent) on docetaxel.; Commonest grade 3 or worse events with sotorasib were diarrhoea (12 percent) and raised alanine (8 percent) and aspartate (5 percent) aminotransferase.
- What it means: KRAS is druggable, and the first generation of drugs is not very good. The gap between the biological achievement and the clinical gain is what the next generation of KRAS inhibitors, and the combination trials around them, exist to close.
- Caveats: Open-label, with progression-free survival as the primary endpoint and no overall survival benefit shown.; Patients with new or progressing untreated brain lesions were excluded.; Docetaxel is a weak comparator, and both arms perform poorly; the trial does not establish a new standard so much as a new option.

## Sources

- Lancet 2023: https://doi.org/10.1016/S0140-6736(23)00221-0
- PubMed: https://pubmed.ncbi.nlm.nih.gov/36764316/
- ClinicalTrials.gov NCT04303780: https://clinicaltrials.gov/study/NCT04303780

## Connected records

- key papers: [Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable](https://onco.cc/key-papers/paper-ostrem-kras-g12c-nature-2013/), [Sotorasib for Lung Cancers with KRAS p.G12C Mutation](https://onco.cc/key-papers/paper-kras-nsclc-n-engl-j-med-2021/)
- roadmaps: [KRAS roadmap: undruggable → G12C → pan-RAS](https://onco.cc/roadmaps/kras-roadmap/), [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- cancers: [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- drugs: [Adagrasib](https://onco.cc/drugs/adagrasib/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Sotorasib](https://onco.cc/drugs/sotorasib/)
- companies: [Amgen](https://onco.cc/companies/amgen/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- trials: [CodeBreaK 100 (pancreatic cancer cohort)](https://onco.cc/trials/codebreak-100/), [CodeBreaK 200](https://onco.cc/trials/codebreak-200/)
- people: [Luis Paz-Ares](https://onco.cc/people/luis-paz-ares/), [Solange Peters](https://onco.cc/people/solange-peters/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/), [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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