Investigational agent fruquintinib holds promise as a third- or fourth-line treatment option for patients with advanced non–small-cell lung cancer (NSCLC), according to new findings published in the Journal of Clinical Oncology.

The median progression free survival (PFS) as evaluated by a blinded image central review committee and the study’s primary endpoint, was more than threefold higher than observed with placebo; 3.8 months (95% confidence interval, 2.8 to 4.6 months) with fruquintinib versus 1.1 months (95% CI, 1.0 to 1.9 months) with placebo (stratified HR was 0.34 (95% CI,0.20 to 0.57; P less than .001). PFS assessed by investigators was nearly identical.

Median overall survival, however, was numerically longer for patients in the placebo arm versus the fruquintinib arm (7.7 and 9.7 months in the fruquintinib and placebo groups; stratified HR, 0.70; 95% CI, 0.43 to 1.15; P = .152). The authors point out that overall survival is a secondary endpoint and the study was insufficiently powered to assess differences in overall survival.

“In 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,” wrote Dr. Shun Lu of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Jiao Tong University, Shanghai, China, and colleagues.

Fruquintinib is a highly selective inhibitor of VEGFR-1, -2 and -3 kinases, and showed promising activity against solid tumors, including NSCLC, in a phase 1 trial. The current phase 2 trial evaluated the efficacy and safety of single-agent fruquintinib in 91 patients with advanced nonsquamous NSCLC. All patients had experienced disease progression after two lines of standard chemotherapy, and were randomly assigned to be treated with either fruquintinib (n = 61) or placebo (n = 30).

At data cutoff for PFS analysis, a total of 46 patients (75.4%) in the fruquintinib group and 25 (83.3%) in the placebo group had experienced a PFS event. The median follow-up for survival was 28.0 months for fruquintinib and 25.4 months for the placebo group.

Both the 3- and 6-month survival rates were numerically higher for patients receiving fruquintinib group versus placebo (90.2% vs. 73.3% for 3-month survival and 67.2% vs. 58.8% for 6-month survival).

The results for other secondary endpoints showed a more favorable overall response rate for fruquintinib vs placebo (13.1% vs 0%; P = .041), as was the disease control rate (60.7% vs 13.3%; P less than .001).

Subgroup analyses favored PFS with fruquintinib, as it was significantly longer vs. placebo for all patient subsets except for those with brain metastases. The median overall survival also was numerically greater with fruquintinib among patients positive for EGFR mutations (8.4 vs. 5.5 months; HR, 0.58; 95% CI, 0.30-1.141 P =.11).

Treatment emergent adverse events were higher in the fruquintinib arm (100% vs. 90%), but most of these were grade 1/2 in both groups. The most common grade 3 and higher events observed with fruquintinib were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%).

SOURCE: Lu S. et al. J Clin Oncol. 2018 Mar. 12 doi: 10.1200/JCO.2017.76.7145 .