Melissa Johnson, MD, Tennessee Oncology, Nashville, discusses results from the phase 3 CodeBreaK 200 trial comparing sotorasib vs docetaxel for patients with previously treated non-small cell lung cancer (NSCLC) with a KRAS G12C mutation.

These results were presented at the 2022 ESMO Annual Meeting.

Transcript:

My name is Dr Melissa Johnson. I'm the director of the Lung Cancer Research Program for Sarah Cannon and a medical oncologist with Tennessee Oncology and One Oncology. At [ESMO] 2022, I presented the CodeBreak 200 pivotal study. Was a randomized phase three trial global effort to enroll patients with previously treated NSCLC harboring a KRAS G12C mutation.

Patients were randomized 1:1 to receive sotorasib, an oral direct KRAS G12C inhibitor, vs IV docetaxel once every 3 weeks. The primary end point was PFS, with key secondary end points including safety, tolerability, patient reported outcomes, and overall survival.

There were initially 650 patients planned, but when the CodeBreak 100 trial results were presented a year ago, the FDA asked that the study be amended. The sample size was decreased by half and crossover was allowed. CodeBreak 200 met its primary end point improving progression-free survival over IV docetaxel alone. Patients treated with sotorasib had a 34% decrease rate of disease progression or death compared to patients treated with the IV chemotherapy.

In addition, sotorasib was better tolerated than IV chemotherapy. IV chemotherapy has all the side effects that we know about, cytopenias, hair loss, neuropathy. And sotorasib, while it does have some low-grade nausea and transaminase elevation, it was very well tolerated and if you were skeptical about this, you can also see that superior tolerance looking at the patient reported outcomes, where patients that were treated with sotorasib reported a decreased rate of disease related symptoms and improved quality of life vs docetaxel initially upon starting the trial, and over time reported slowing of clinical deterioration relative to docetaxel.

Given the totality of all the data, the decreased risk of recurrence, the better tolerability, this was a positive trial for sure. The controversial part of CodeBreak 200 was in the overall survival results. There was no difference. Hazard ratio 1.01 and a P-value of 0.5. But remember that the trial was amended and the sample size was reduced by half. And in so doing, CodeBreak 200 lost its statistical power to look at overall survival.

The overall survival analysis was underpowered and patients were allowed to cross over. 34% of patients who were randomized to docetaxel went on to receive sotorasib or another KRAS G12C inhibitor afterwards, and that was captured in the trial results. There was another 13% of patients who, when randomized to docetaxel, declined to participate, and presumably some of them also went on to receive oral TKIs targeting KRAS G12C elsewhere.

In summary, CodeBreak 200 met its primary end point, decreasing the risk of disease progression or death when patients were treated with oral sotorasib. In my opinion, this trial gives us confidence to use sotorasib as a second line standard of care for our patients with NSCLC harboring KRAS G12C mutations.

Source:

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 Congress; September 9-13, 2022; Paris, France. Abstract LBA10.