Long follow-up
The long-term data reported at the 2022 meeting by Dr. Dy and colleagues included data on 48 patients enrolled in phase 1 of the trial, which had a primary endpoint of safety and tolerability, and 126 patients enrolled in phase 2, with a primary endpoint of objective response rate by blinded independent review.
The trial was conducted in centers in the United States, Europe, Australia, Japan, and South Korea.
Nearly all patients were pretreated: 92.5% of patients had received prior platinum-based chemotherapy and 90.2% had received anti–PD-1/PD-L1 immunotherapy.
Patients received oral sotorasib 960 mg once daily and were followed with radiographic scans every 6 weeks for the first year and once every 12 weeks thereafter.
Of the 174 patients enrolled, two were not evaluable for response at 2 years because of a lack of measurable lesions at baseline.
At a median follow-up of 24.9 months, 5 patients (2.9%) had a complete response and 65 (37.8%) had a partial response, for an objective response rate of 40.7%. An additional 74 patients (43%) had stable disease, for a disease control rate of 83.7%. Of the remaining patients, 23 (13.4%) had disease progression, and 5 were either not evaluable or had missing scan data.
Median progression-free survival was 6.3 months. Median time to response was 6 weeks, and median duration of response was 12.3 months. Half of patients who had a response retained that response for at least 12 months.
Median OS was 12.5 months. The 1-year and 2-year OS rates were 50.8% and 32.5%, respectively.
Grade 3 or 4 treatment-related adverse events occurred in 21% of patients, and one patient had new-onset grade 3 hemolytic anemia 1 year after starting therapy. There were no treatment-related deaths and no treatment-related adverse events leading to discontinuation after the first year.
In exploratory analyses, the benefit of the drug was seen across tumors with varying levels of PD-L1 expression and the oncogenic STK11 comutation, and across KRASG12C variant allele frequency.
The investigators also reported that baseline circulating tumor DNA levels correlated with tumor burden, and that patients who had long-term benefits had lower baseline ctDNA. This finding is consistent with the documented role of ctDNA as a marker for poor prognosis regardless of therapy.
Dr. Dy reported receiving consulting fees from AstraZeneca, Eli Lilly, Mirati Therapeutics, and Takeda in the past 2 years. Dr. Yap disclosed receiving consulting fees from multiple companies. Dr. Awad disclosed consulting for multiple companies.
A version of this article first appeared on Medscape.com.