Sotorasib Safe, Effective for KRAS p.G12C-mutated NSCLC

According to findings from a phase 2 trial, sotorasib therapy was effective and raised no safety concerns in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC; N Engl J Med. 2021 Jun 4.)

In a phase 1 study, sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors, with promising activity in a subgroup of patients with NSCLC.

With this in mind, Ferdinandos Skoulidis, MD, PhD, the University of Texas M.D. Anderson Cancer Center, Houston, and colleagues conducted a single-group, phase 2 trial to investigate the activity of sotorasib. 

Patients with KRAS p.G12C–mutated advanced NSCLC previously treated with standard therapies received 960mg of sotorasib, administered orally once daily. 

The primary end point was an objective response (complete or partial) according to independent central review, secondary end points included duration of response, disease control (defined as complete response, partial response, or stable disease), progression-free survival (PFS), overall survival (OS), and safety. 

Of the 126 patients enrolled, 81.0% received prior treatment of both platinum-based chemotherapy and PD-1or PD-L1 inhibitors. Furthermore, 124 patients had measurable disease at baseline and were evaluated for response. An objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), with a complete response in 4 (3.2%) and partial response in 42 (33.9%).

The median duration of response was 11.1 months (95% CI, 6.9 to could not be evaluated), with disease control in 100 patients (80.6%; 95% CI, 72.6 to 87.2). The median PFS and OS were 6.8 months (95% CI, 5.1 to 8.2) and 12.5 months (95% CI, 10.0 to could not be evaluated)l, respectively. 

Although 88 of 126 patients (69.8%) experienced treatment-related adverse events (AEs), AEs of grade 3 were observed in 25 patients (19.8%), and a single patient had a grade 4 event (0.8%). 

“In this phase 2 trial, sotorasib therapy led to a durable clinical benefit without new safety signals in patients with previously treated KRAS p.G12C–mutated NSCLC,” concluded Dr Skoulidis et al. —Alexandra Graziano


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