In the Japanese phase II T-ACT study reported in the Journal of Clinical Oncology, Makiyama et al found no benefit of continued trastuzumab combined with paclitaxel after disease progression on first-line trastuzumab plus fluoropyrimidine/platinum chemotherapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer.
Study Details
In the multicenter open-label trial, 91 patients refractory to first-line trastuzumab in combination with fluoropyrimidine/platinum chemotherapy were randomly assigned to receive paclitaxel at 80 mg/m2 on days 1, 8, and 15 every 28 days with (n = 45) or without (n = 46) continued trastuzumab (initial 8 mg/kg dose, followed by 6 mg/kg every 3 weeks). The primary endpoint was progression-free survival.
Efficacy Outcomes
Median duration of follow-up was 10 months in both groups. Median progression-free survival was 3.2 months in the paclitaxel group vs 3.7 months in the paclitaxel/trastuzumab group (hazard ratio [HR] = 0.91, P = .33). Median overall survival was 10.0 months vs 10.2 months (HR = 1.23, P = .20). Objective response rates were 32% vs 33% (P = 1.00).
In exploratory analyses, HER2 positivity of tumor tissue was lost after first-line chemotherapy in 11 (69%) of 16 patients with available tumor tissue, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients with available data. No associations between biomarkers and efficacy of continued trastuzumab plus paclitaxel were identified.
Adverse Events
Grade ≥ 3 adverse events in the paclitaxel vs paclitaxel/trastuzumab groups included neutropenia (27% vs 33%), anemia (24% vs 31%), leukopenia (18% vs 29%), peripheral sensory neuropathy (7% vs 7%), and anorexia (7% vs 4%). Any-grade anorexia was more common in the paclitaxel/trastuzumab group (47% vs 29%). No severe cardiac adverse events were observed in the paclitaxel/trastuzumab group.
The investigators concluded: “The trastuzumab beyond progression strategy failed to improve [progression-free survival] in patients with HER2-positive advanced gastric or gastroesophageal junction cancer, and no beneficial biomarkers were found.”
Disclosure: The study was supported by the Cancer Clinical Trial Research Grant Program of the Japan Society of Clinical Oncology. For full disclosures of the study authors, visit ascopubs.org.
