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May 27, 2020 06:00pm
By Lisa Astor
TAS-102 improved overall survival in patients with metastatic gastric/gastroesophageal junction cancer, regardless of prior gastrectomy, according to a preplanned subgroup analysis from the phase III TAGS trial published in JAMA Oncology.
David H. Ilson, MD, PhD
TAS-102 (trifluridine/tipiracil; FTD/TPI; Lonsurf) improved overall survival (OS) in patients with metastatic gastric/gastroesophageal junction (GEJ) cancer, regardless of prior gastrectomy, according to a preplanned subgroup analysis from the phase III TAGS trial published inJAMA Oncology.1,2
Data from the analysis, which were previously presented in January at the 2019 Gastrointestinal Cancers Symposium, showed that treatment with TAS-102 was associated with a median OS of 6.0 months in patients with prior gastrectomy, as compared with 3.4 months in the placebo-treated patients with prior gastrectomy (HR, 0.57; 95% CI, 0.41-0.79). The median PFS was 2.2 versus 1.8 months, respectively (HR, 0.48; 95% CI, 0.35-0.65).
Among patients who had not received a gastrectomy, the median OS was 5.6 months with TAS-102 versus 3.8 months with placebo (HR, 0.80; 95% CI, 0.60-1.06). The median PFS was 1.9 versus 1.8 months, respectively (HR, 0.65; 95% CI, 0.49-0.85).
These data were similar to the findings of the primary study analysis. In the overall population, the median OS was 5.7 months versus 3.6 months (HR, 0.69; 95% CI, 0.56-0.85;P= .0003, one sided; P= .0006, two sided) with TAS-102 versus placebo, respectively. The median PFS was 2.0 versus 1.8 months, respectively (HR, 0.57; 95% CI, 0.47-0.70; P<.0001, two sided).
Based on the primary analysis, the FDA approved TAS-102 in February 2019 for the treatment of adult patients with metastatic gastric or GEJ adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.
"The outcome of the phase III TAGS trial in this patient population is extremely significant, as nearly half of all patients with metastatic gastric cancer and gastroesophageal junction adenocarcinoma have undergone a previous gastrectomy and are prone to more complications than those without gastrectomy," lead investigator David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, said in a press release. "These data provide further evidence of the safety and efficacy of Lonsurf and its utility in patients who may have limited treatment options."
The global phase III 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 ≥2 prior chemotherapy regimens. Patients were randomized 2:1 to receive TAS-102 (35 mg/m2twice daily on days 1 to 5 and 8 to 12 of each 28-day cycle) or placebo plus best supportive care, and were treated until progression, intolerability, or patient withdrawal.
The primary cancer site was gastric in 71% and GEJ in 29%. Fifty-five percent had ≥3 metastatic sites. Sixty-three percent in each arm had ≥3 prior treatments and 44% in each arm had prior gastrectomy. More than 90% received prior platinum, fluoropyridine, and taxane treatment. About one-third in each arm had prior ramucirumab.
Overall, 221 patients had undergone gastrectomy (147 randomized to TAS-102 and 74 to placebo). Of these, 153 (69.2%) had total resection and 56 (25.3%) had partial resection. For 12 (5.4%) patients, the resection status was not known. Patients characteristics at baseline were similar between the gastrectomy and no-gastrectomy subgroups.
Among patients treated with TAS-102, grade ≥3 adverse events (AEs) occurred in 84.1% of the gastrectomy group and in 76.3% of patients who did not receive gastrectomy. The rates of grade ≥3 neutropenia (44.1% vs 26.3%), anemia (21.4% vs 17.4%), and leukopenia (14.5% vs 5.3%) were all higher in in the gastrectomy group. Adverse events led to dosing modifications in 64.8% of the gastrectomy group compared with 53.2% of the no-gastrectomy group. Discontinuations due to AEs occurred in 10.3% versus 14.7% of the two groups, respectively.
TAS-102 is also approved for the treatment of patients with metastatic colorectal cancer who have received fluoropyrimidine-, oxaliplatin- , and irinotecan-based chemotherapy, an anti-VEGF biologic product, and an anti-EGFR monoclonal antibody, ifRASwild-type.