J Gastric Cancer.  2023 Oct;23(4):609-621. 10.5230/jgc.2023.23.e41.

Efficacy and Safety of Trastuzumab Deruxtecan and Nivolumab as Third- or Later-Line Treatment for HER2-Positive Advanced Gastric Cancer: A SingleInstitution Retrospective Study

• Shimozaki K
• Nakayama I
• Takahari D
• Nagashima K
• Yoshino K
• Fukuda K
• Fukuoka S
• Osumi H
• Ogura M
• Wakatsuki T
• Ooki A
• Shinozaki E
• Chin K
• Yamaguchi K

• KMID: 2547771
• DOI: http://doi.org/10.5230/jgc.2023.23.e41

Abstract

Purpose
Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments.
Materials and Methods
This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years; 69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38).
Results
Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd–nivolumab and nivolumab–T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively.
Conclusions
T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.

Keyword

HER2; Nivolumab; Gastric cancer; Trastuzumab deruxtecan