FDA Approves Lonsurf for Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

The Food and Drug Administration (FDA) has approved Lonsurf (TAS-102; trifluridine/tipiracil) for adult patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least two prior lines of chemotherapy.

The approval is based on data from the phase 3 TAGS trial, in which Lonsurf reduced the risk of death by about one-third compared with placebo in patients with heavily pretreated gastric or GEJ cancer. The TAGS trial also showed improvements in progression-free survival and disease control, and demonstrated a predictable and manageable safety profile.

“Effective treatments for patients with heavily pretreated advanced gastric and GEJ cancer are limited,” Martin Birkhofer, M.D., senior vice president and chief medical officer at Taiho Oncology, Inc., said in a press release. “By improving survival, Lonsurf may provide a significant impact on the lives of these patients.”

TAGS was conducted to confirm findings from a phase 2 Japanese study in patients with metastatic gastric cancer in which Lonsurf was evaluated after failure of standard chemotherapies or irinotecan and found to lead to a median overall survival of 8.7 months and a disease control rate of 65.5 percent.

The global phase 3 TAGS double-blind study enrolled 507 adults with histologically confirmed, nonresectable metastatic gastric/GEJ cancer and an ECOG performance status of 0 or 1 who received two or more prior chemotherapy regimens. Patients were randomized 2:1 to receive Lonsurf or placebo plus best supportive care, and were treated until progression, intolerability, or patient withdrawal.

The primary cancer site was gastric in 71 percent and GEJ in 29 percent. Fifty-five percent had three or more metastatic sites. Sixty-three percent in each arm had three or more prior treatments and 44 percent in each arm had prior gastrectomy. More than 90 percent received prior platinum, fluoropyridine, and taxane treatment. About one-third in each arm had prior ramucirumab.

Median overall survival, the primary endpoint, was 5.7 months for patients assigned to Lonsurf compared with 3.6 months for patients randomized to placebo. The 12-month overall survival rate for the TAS-102 group was 21 percent versus 13 percent for the placebo group.

Median progression-free survival, a secondary endpoint, was also significantly improved with Lonsurf compared with placebo. The six-month progression-free survival rates were 15 percent and 6 percent, respectively. The progression-free survival advantage for TAS-102 was maintained when assessed by subgroups based on age, region, ethnicity, ECOG performance status, primary site, number of metastatic sites, and prior treatment with ramucirumab, among others.

The objective response rate with Lonsurf was 4 percent compared with 2 percent for placebo. In the active treatment group, there was one complete response, 12 partial responses and 115 patients with stable disease, for a disease control rate of 44 percent. The disease control rate in the placebo group was 14 percent.

Grade 3 or higher side effects of any cause occurred in 80 percent of patients on Lonsurf versus 58percent of those assigned to placebo. Lonsurf was associated with more treatment-related side effetcs of any grade (81 percent vs 57 percent). There was one treatment-related death in each group. Grade 3 or higher febrile neutropenia of any cause was reported in six (2 percent) patients treated with Lonsurf.

Dosing modification (dose delay or reduction) to manage side effects was required in 58 percent of the Lonsurf group. Treatment had to be discontinued due to adverse events in 13 percent. G-CSF treatment to manage neutropenia was necessary in 16 percent. The most common side effects leading to dosing modification were neutropenia and/or decreased neutrophil count (37 percent), anemia and/or decreased hemoglobin level (9 percent) and leukopenia and/or decreased white blood cell count (6 percent).

This article originally appeared on OncLive as, “FDA Approves TAS-102 for Gastric/GEJ Cancer.”