Fruquintinib as a third- or fourth-line therapy appeared safe and superior to placebo among patients with advanced non-small cell lung cancer, according to results of a randomized, double-blind, placebo-controlled phase 2 study conducted in China.
“In patients with genetic alterations, such as EGFR mutations or anaplastic lymphoma kinase fusions, first-line treatment with molecular targeted agents can improve PFS,” Shun Lu, MD, of Shanghai Lung Cancer Center at Shanghai Chest Hospital, and colleagues wrote.
However, the researchers added, such disease often develops resistance to chemotherapy.
“Chemotherapy has reached a therapeutic plateau, and the prognosis for patients whose disease progresses after chemotherapy remains poor,” they added. “There remains a major unmet need for effective and well-tolerated treatment options for patients with advanced NSCLC who have experienced treatment failure with chemotherapy and/or molecular targeted therapies.”
The analysis included 91 patients with advanced NSCLC treated at 12 hospitals who had experienced disease progression after second-line chemotherapy. Lu and colleagues randomly assigned patients 2:1 to receive either fruquintinib (Hutchison Medi Pharma) or placebo stratified by EGFR status.
Patients assigned fruquintinib received 5 mg once daily in 4-week cycles. Each cycle consisted of treatment for 3 weeks followed by 1 week off.
PFS as assessed by a blinded image central review committee served as the main outcome. Secondary outcomes included investigator-evaluated PFS, disease control rate, OS, objective response rate and safety.
In both investigators’ and committee assessments, patients assigned fruquintinib had a median PFS of 3.8 months, compared with 1.1 months in the placebo group (HR = 0.34; 95% CI, 0.2-0.57).
Survival rates were higher in the fruquintinib group at 3 months (90.2% vs. 73.3%) and 6 months (67.2% vs. 58.8%).
Researchers observed a higher ORR (13.1% vs. 0%; P = .041) and disease control rate (60.7% vs. 13.3%; P < .001) with fruquintinib.
The most common grade 3 or higher treatment-emergent adverse events with fruquintinib included hypertension (8.2%), followed by hand-foot syndrome (4.9%) and proteinuria (4.9%).
“[Among] patients with NSCLC who experienced treatment failure with two standard chemotherapies, fruquintinib may provide a clinically meaningful benefit, and further evidence of a statistically significant OS benefit of fruquintinib is expected from a phase 3 randomized study in this target population,” Lu and colleagues wrote. – by Andy Polhamus
Disclosures: Lu reports honoraria from AstraZeneca, Eli Lilly and Roche; consulting/advisory roles with AstraZeneca, Boehringer Ingelheim and Roche; and research funding from AstraZeneca, Hutchison MediPharma and Roche. Please see the full study for all other authors’ relevant financial disclosures.