Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study...

Area of Science:

• Oncology
• Gastroenterology
• Pharmacology

Background:

• Advanced gastric cancer (AGC) remains a significant health challenge with limited second-line treatment options.
• Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) overexpression are observed in a subset of AGC patients.
• Targeted therapies are being investigated to improve outcomes in AGC.

Purpose of the Study:

• To evaluate the safety and efficacy of a combination therapy with varlitinib and paclitaxel.
• To assess varlitinib and paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer.
• To determine the recommended phase II dose (RP2D) for this combination therapy.

Main Methods:

• A phase Ib/II study design was employed.
• Patients with EGFR and HER2 overexpression (≥ 1+ by immunohistochemistry) were enrolled.
• Varlitinib and paclitaxel were administered every 4 weeks, with dose escalation in phase Ib to determine RP2D.

Main Results:

• The RP2D was varlitinib (300 mg twice daily) combined with paclitaxel.
• Median progression-free survival was 3.3 months and median overall survival was 7.9 months in 27 patients.
• Objective response rate was 31% in patients with measurable disease; higher response and survival were noted in patients with strong HER2 expression.

Conclusions:

• The combination of varlitinib and paclitaxel demonstrated manageable toxicity and modest antitumor activity.
• This regimen represents a potential therapeutic option for patients with EGFR/HER2 co-expressing AGC progressing after first-line chemotherapy.
• Further investigation may be warranted, particularly in subgroups with strong HER2 expression.