According to data being presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, second-line therapy with trastuzumab plus ramucirumab and paclitaxel showed promising activity and manageable safety in patients with HER2-positive gastric or gastroesophageal junction (GI/GEJ) cancer that progressed after trastuzumab-containing chemotherapy.

“We evaluated the safety and efficacy of adding trastuzumab to ramucirumab and paclitaxel as a second line treatment in HER2-positive advanced gastric or gastroesophageal junction (GI/GEJ) cancer progressed from trastuzumab containing chemotherapy,” explained Sun Young Rha, MD, PhD, Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, et al.

“After safety analysis of lead-in safety cohort (phase 1b), phase 2 part was conducted to evaluate the primary end point of progression-free survival (PFS),” they continued.

During the phase 1b portion of the study, there was no dose-limiting toxicity in 3 patients receiving trastuzumab 4 mg/kg on day 1 followed by 2 mg/kg on days 8, 15, and 22 plus ramucirumab 8 mg/kg on days 1 and 15 and paclitaxel 80mg/m² on days 1, 8, and 15. Thus, this was determined as recommended phase 2 regimen.

Objective response rate (ORR), disease control rate, overall survival (OS), and safety were among the secondary end points.

As of January 31, 2021, a total of 45 patients of 50 enrolled in the study were evaluable for response and safety, including 3 who participated in phase 1b (median age, 59 years).

“At baseline, 33 patients had tumors with HER-2 3+ by immunohistochemistry (IHC) and 12 had those with HER-2 2+ by IHC with ERBB2 amplification by in situ hybridization. With median follow-up duration of 11.6 months, median PFS and OS were 7.2 months (95% CI, 6.0-8.5 months) and 13.6 months (95% CI, 10.3-16.9 months), respectively,” Dr Rha and colleagues reported.

Among the evaluable patients, the ORR was 55.6%, with 1 complete response and 2 partial responses, and the disease control rate was 95.6%.

The most frequently reported hematologic adverse event (AE) was neutropenia (all grade, 64.4%; grade 3/4, 51.1%) with 1 (2.2%) case of febrile neutropenia. With regard to non-hematologic AEs, peripheral sensory neuropathy was the most common, (all grade, 33.3%; grade 3, 2.2%).

Although GI bleeding occurred in 4 patients, GI perforation was not observed. A total of 3 patients had hypertension, but no new or unexpected AEs leading to treatment cessation were documented.

“The continuous use of trastuzumab beyond progression in combination with ramucirumab and paclitaxel showed promising activity and manageable safety profile in HER2-positive GI/GEJ cancer patients who progressed after trastuzumab containing chemotherapy,” Dr Rha and colleagues concluded.

Rha SY, Kim CG, Jung M, et al. Multicenter phase Ib/II study of second-line trastuzumab, ramucirumab, and paclitaxel in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (HER-RAM study). Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 4063.