In an interim analysis of a Chinese phase III trial (SACHI) reported in The Lancet, Lu et al found that the combination of savolitinib and osimertinib prolonged progression-free survival vs chemotherapy in patients with advanced EGFR-mutated, MET-amplified non–small cell lung cancer (NSCLC).
Study Details
In the multicenter open-label trial, 211 patients whose disease had progressed on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy were randomly assigned between October 2021 and August 2024 to receive: savolitinib at a weight-based dosing of 600 mg if ≥ 50 kg or at 400 mg if < 50 kg plus osimertinib at 80 mg once daily in 21-day cycles (n = 106); or chemotherapy consisting of pemetrexed at 500 mg/m² plus either cisplatin at 75 mg/m² or carboplatin at AUC = 5 on day 1 of each 21-day cycle for 4 to 6 cycles, with pemetrexed maintenance permitted in patients without progression (n = 105). A total of 137 patients, including 69 in the savolitinib plus osimertinib group and 68 in the chemotherapy group, were third-generation EGFR tyrosine kinase inhibitor–naive. The primary endpoint was investigator-assessed progression-free survival, tested first in the third-generation EGFR tyrosine kinase inhibitor–naive population and, if positive, then in the intention-to-treat (ITT) population.
Key Findings
In the third-generation EGFR tyrosine kinase inhibitor–naive population, median progression-free survival was 9.8 months (95% confidence interval [CI] = 6.9–12.5 months) in the savolitinib plus osimertinib group vs 5.4 months (95% CI = 4.2–6.0 months) in the chemotherapy group (hazard ratio [HR] = 0.34, 95% CI = 0.21–0.56, P < .0001).
In the ITT population, median progression-free survival was 8.2 months (95% CI = 6.9–11.2 months) in the savolitinib plus osimertinib group vs 4.5 months (95% CI = 3.0–5.4 months) in the chemotherapy group (HR = 0.34, 95% CI = 0.23–0.49, P < .0001).
Grade 3 or worse adverse events occurred in 57% of the savolitinib plus osimertinib group and 57% of the chemotherapy group; common events (occurring in at least 10% of either group) included neutrophil count decrease (14% vs 26%), white blood cell count decrease (7% vs 13%), and anemia (4% vs 23%). Serious adverse events occurred in 38% vs 28% of patients. Treatment-related death occurred in two patients in the savolitinib plus osimertinib group.
The investigators concluded: “The savolitinib–osimertinib combination improved [progression-free survival] versus chemotherapy in patients with EGFR mutation-positive, MET-amplified NSCLC that had progressed on EGFR [tyrosine kinase inhibitor] therapy, while maintaining a favourable tolerability profile. This regimen offers a potential oral treatment option for this biomarker-selected population.”
Shun Lu, MD, of Shanghai Jiao Tong University, School of Medicine, Shanghai, and Jie Wang, MD, of Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, are the corresponding authors for The Lancet article.
DISCLOSURE: The study was funded by HUTCHMED and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
