Sotorasib shows superior PFS and ORR over docetaxel in previously treated NSCLC

Improvement seen in progression-free survival and ORR by the selective KRAS G12C inhibitor over docetaxel in previously treated KRAS G12C-mutated NSCLC.

Cross-over to sotorasib following disease progression was allowed

KRAS mutations have been associated with poor prognosis and occur in approximately 1 in 4 patients diagnosed with NSCLC, with KRASG12C harboured at approximately 11–16%1. Previously, the phase 1/2 CodeBreak 100 study (NCT03600883) showed promising PFS, ORR, and overall survival (OS) in patients with KRASG12C-mutated NSCLC treated with the (oral) selective KRASG12C inhibitor sotorasib2.

The phase 3 CodeBreak 200 study (NCT04303780) evaluated efficacy and safety of sotorasib versus docetaxel in previously treated KRASG12C-mutated NSCLC patients. Dr Melissa Johnson (Sarah Cannon Research Institute, TN, USA) presented the results3.

CodeBreak 200 enrolled a total of 345 KRASG12C-mutated NSCLC patients who had at least 1 prior therapy, including platinum-based chemotherapy and checkpoint inhibition. Participants were 1:1 randomised to receive sotorasib (960 mg daily) or docetaxel (75 mg/m2 every 3 weeks). Cross-over to sotorasib following disease progression was allowed. The primary endpoint was PFS; secondary endpoints were OS, ORR, time to response (TTR), duration of response, and safety. 

CodeBreak 200 was not powered to detect a significant difference in OS

With a median follow-up of 117.7 months, median PFS for participants in the sotorasib arm was 5.6 months versus 4.5 months for participants in the docetaxel arm (HR 0.66; P=0.002). PFS rates at 12 months were 24.8% and 10.1%, respectively. ORR was 28.1% versus 13.2% in participants treated sotorasib and docetaxel, respectively. Median TTR was 1.4 months versus 2.8 months, and median duration of response was 8.6 months versus 6.8 months in the sotorasib and docetaxel arm, respectively.

There was no difference in OS between the two treatment arms (HR 1.01). However, due to an amendment to the study protocol, CodeBreak 200 was not powered to detect a significant difference in Overall Survival. Of note, 34% of patients treated with docetaxel crossed over to sotorasib.

Sotorasib was well-tolerated with a lower incidence of grade 3 or higher treatment-related adverse events compared with docetaxel. Time to deterioration in global health status, physical functioning, and cancer-related symptoms were delayed with sotorasib compared with docetaxel. “These findings support sotorasib as an important treatment option in this setting and reinforce the importance of testing for KRAS G12C mutations,” concluded Dr Johnson.

  1. Palma G, et al. NPJ Precis Oncol. 2021;5:98.
  2. Dy GK, et al. Abstract CT008, AACR Annual Meeting 2022, New Orleans, LA, USA, 08–13 April.
  3. Johnson ML, et al. Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study. Abstract LBA10, ESMO Congress 2022, Paris, France, 09–13 September.