Trastuzumab Plus Ramucirumab and Paclitaxel Shows Promise Among Patients With Second-Line HER2-Positive, Advanced Gastric or Gastroesophageal Junction Cancer

According to a phase 1b/2 study, trastuzumab plus ramucirumab and paclitaxel demonstrated efficacy and consistent safety among patients with previously treated human epidermal growth factor receptor 2-positive (HER2-positive) gastric or gastroesophageal junction cancer (G/GEJC).

This phase 1b/2 study enrolled 50 patients with HER2-positive advanced G/GEJC who had progressed on or after first-line treatment with trastuzumab-containing chemotherapy. All patients received trastuzumab on days 1, 8, 15 and 22 at 2 mg/kg followed by 4 mg/kg loading dose, 8 mg/kg ramucirumab on days 1 and 15, and paclitaxel on days 1, 8, and 15, in 28-day cycles. Paclitaxel was delivered in one of two dose levels: either at 80mg/m² or 70mg/m².

The primary end point of phase 1 was the determination of the recommended phase 2 dose and of phase 2 was investigator-assessed progression-free survival (PFS) of all patients treated with that recommended dose. The full dose option (80 mg/m² of paclitaxel) was selected as the recommended phase 2 dose. With a median follow-up duration was 27.5 months, the median PFS was 7.1 month and the median overall survival was 13.6 months. The objective response rate was 96% (n = 48), with 1 complete response. The disease control rate was also 96%. In 34.8% of patients, HER2 express was lost following first-line treatment. However, there was no definitive association found between HER2 expression and outcome. Safety was consistent with previous reports.

Study authors concluded “trastuzumab combined with ramuxirumab plus paclitaxel showed appreciable efficacy with manageable safety profiles” within this patient population.

Journal of Clinical Oncology associate editor, Andrew H. Ko, MD, Hellen Diller Family Comprehensive Cancer Center at University of California, San Francisco, California, added, “Continuation of trastuzumab in the second-line setting, in combination with paclitaxel/ramucirumab, represents a promising strategy for patients with advanced HER2-positive gastroesophageal cancer.” Dr Ko also noted that further prospective randomized data are needed to validate this regiment.

Source:

Kim CG, Jung M, Kim HS, et al. Trastuzumab combined with ramucirumab and paclitaxel in patients with previously treated human epidermal growth factor receptor 2-positive advanced gastric or gastroesophageal junction cancer. J Clin Oncol. Published on June 26, 2023. doi:10.1200/JCO.22.02122