Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. Patients allocated to the sotorasib group reported increased progression-free survival compared to the docetaxel group.

2. Sotorasib was generally tolerable with diarrhea being the most common severe adverse event.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Docetaxel is combined with immunotherapy to treat locally advanced non-small-cell lung cancer (NSCLC) with evidence of disease progression. A large proportion of patients with NSCLC report positive for KRASG12C mutations. In such cases, sotorasib – a molecule that irreversibly inhibits the KRASG12C protein – may be more effective. This randomized controlled trial aimed to compare the safety and efficacy of sotorasib with docetaxel in patients with KRASG12C-positive NSCLC who were previously treated with other anticancer drugs, such as platinum-based chemotherapy and immunotherapy. The primary outcome was progression-free survival while key secondary outcomes included overall survival, duration of response, and patient-reported outcomes. According to study results, sotorasib resulted in significantly improved clinical outcomes with greater progression-free survival compared with docetaxel. Overall, patients randomized to sotorasib reported fewer serious adverse events with diarrhea being the most common within this treatment group. This study was strengthened by a randomized design with patients from multiple countries, thus increasing its generalizability.

In-depth [randomized-controlled trial]:

Between Jun 4, 2020, and Apr 26, 2021, 616 patients were assessed for eligibility across 148 centers in 22 countries. Included were patients ≥ 18 years with KRASG12C-positive locally advanced and unresectable or metastatic NSCLC. Altogether, 345 patients (171 in sotorasib and 175 in docetaxel) were included in the intention-to-treat analysis. The primary outcome of progression-free survival was significantly greater in the sotorasib group (5.6 months, 95% confidence interval [CI] 4.3-7.8) compared to the docetaxel group (4.5 months, 95% CI 3.0-5.7, hazard ratio [HR] 0.66, p=0.0017). There were fewer serious treatment-related adverse events among patients receiving sotorasib (n=18, 11%) compared to docetaxel (n=34, 23%). Overall, findings from this study were strongly in favor of sotorasib for treatment of locally advanced NSCLC with KRASG12C mutation.

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