Second-line fruquintinib + paclitaxel significantly improves PFS but not OS in advanced gastric or GEJ adenocarcinoma

The findings, which were presented as part of the February 2024 ASCO Plenary Series, showed that the fruquintinib regimen (n = 351) led to a median PFS of 5.6 months (95% CI, 4.6-6.4) vs 2.7 months (95% CI, 2.7-3.5) with paclitaxel alone (n = 352), translating to a 43% reduction in the risk of disease progression or death (HR, 0.57; 95% CI, 0.48-0.68; P < .0001), meeting one of the co-primary end points. At a median follow-up of 31.7 months, fruquintinib plus paclitaxel resulted in a numerical but not statistically significant improvement in median OS vs paclitaxel, at 9.6 months (95% CI, 8.9-10.8) vs 8.4 months (95% CI, 7.8-9.4), respectively (HR, 0.96; 95% CI, 0.81-1.13; P = .6064). It was noted that this could potentially be explained by an imbalance in receipt of subsequent antitumor therapy between the fruquintinib and placebo arms, at 52.7% and 72.2%, respectively.

However, after correcting for confounding effects, fruquintinib plus paclitaxel showcased a trend for OS benefit over paclitaxel alone, irrespective of receipt of subsequent antitumor therapy. Those in the fruquintinib arm who did not receive subsequent treatment (n = 166) experienced a median OS of 6.9 months vs 4.8 months for those in the placebo arm who did not receive subsequent treatment (n = 98; HR, 0.72; 95% CI, 0.53-0.99; P = .0422). Those in the fruquintinib (n = 185) and placebo (n = 254) arms who did receive subsequent treatment experienced median OS of 12.2 months vs 10.0 months, respectively (HR, 0.90; 95% CI, 0.73-1.11; P = 3262).

“Fruquintinib plus paclitaxel could be a promising second-line treatment option for patients with advanced gastric or GEJ adenocarcinoma who have [experienced failure with] fluoropyrimidine- or platinum-containing chemotherapy,” Rui-Hua Xu, MD, PhD, professor of medical oncology and president of the Sun Yat-Sen University Cancer Center in Guangzhou, China, said in a presentation of the data.

Patients with gastric cancer who progress on their first line of treatment are limited to receiving ramucirumab (Cymraza) plus chemotherapy or chemotherapy alone. Alternative options in this setting are needed, Xu said. Fruquintinib—an agent that inhibits VEGFRs 1, 2, and 3— has received regulatory approval in China for use in the third-line treatment of patients with metastatic colorectal cancer (mCRC). More recently, in November 2023, the FDA approved fruquintinib for use in adult patients with mCRC who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy, if they had RAS wild-type disease and was medically appropriate.

Additional efficacy data showed that fruquintinib plus paclitaxel elicited an ORR of 42.5% (95% CI, 37.2%-47.8%) vs 22.4% (95% CI, 18.2%-27.2%) with paclitaxel alone (P < .0001). Among those who responded to the fruquintinib regimen, the complete response rate was 1.4% and the partial response rate was 41.0%; 34.8% of patients achieved stable disease, 15.7% experienced disease progression, and 7.1% were not evaluable for response.

The DCRs reported in the fruquintinib and placebo arms were 77.2% (95% CI, 72.5%-81.5%) and 56.3% (95% CI, 50.9%-61.5%), respectively (P < .0001). The median DOR with the doublet was 5.5 months (95% CI, 4.6-6.4) vs 3.7 months (95% CI, 3.7-4.6) with paclitaxel alone.