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.
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.
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.
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.