Sotorasib beneficial for certain pancreatic cancers: Study
USA: Sotorasib has shown clinically meaningful anticancer activity and tolerability in heavily pretreated KRASG12C-mutated advanced pancreatic cancer patients, according to recent findings from the CodeBreaK100 trial. Such patients have limited treatment options and poor prognoses. The findings of the study were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium.
KRAS mutation is prevalent in 90% of pancreatic ductal adenocarcinomas with p.G12C accounting for 1% to 2% of these mutations. Sotorasib is a small molecule that specifically and irreversibly inhibits KRASG12C. It has been investigated in the CodeBreaK100 trial for patients with KRASG12C-mutated advanced solid tumors.
In the study, John H Strickler, Duke University Medical Center, Durham, NC, and colleagues report the largest dataset evaluating safety and efficacy of a KRASG12C inhibitor in patients with pretreated KRASG12C-mutated pancreatic cancer.
CodeBreaK100 is an international, single-arm, phase I/II study that evaluates the safety and efficacy of sotorasib in patients with KRASG12C-mutated advanced solid tumors with ≥ 1 prior systemic therapy unless intolerant or ineligible for available therapies. Confirmed objective response rate (ORR), assessed by blinded independent central review (BICR) per RECIST 1.1 is the primary efficacy endpoint. Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
Following were the salient findings of the study:
- As of November 1, 2021, 38 patients with pancreatic cancer (mean age: 65 years, 76.3% male) from the combined phase I/II study received sotorasib 960 mg once daily.
- Stage IV disease was present in 55.3% of patients at diagnosis, and in all patients at enrollment.
- Baseline ECOG scores were 0, 1, or 2 in 31.6%, 57.9%, and 10.5% of patients, respectively.
- Most patients (79%) had ≥ 2 prior lines of therapy (median: 2). The median treatment duration was 4.1 months with a median follow-up of 16.8 months.
- Eight patients had confirmed partial response by BICR with a resulting ORR of 21.1% (95% CI: 9.55%-37.32%).
- DCR was 84.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 16 (42.1%) patients. Grade ≥ 3 TRAEs occurred in 6 patients: diarrhea (2); fatigue (2); abdominal pain, ALT increase, AST increase, pleural effusion, and pulmonary embolism (1 each). No TRAEs were fatal or resulted in sotorasib discontinuation.
"Sotorasib showed clinically meaningful anticancer activity and tolerability in patients with heavily pretreated KRASG12C-mutated advanced pancreatic cancer, who have limited treatment options and poor prognosis," the authors concluded.
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