The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago from May 29 to June 2, 2026, showcased several practice-changing advances in oncology. Among the highlights, Prof. Kohei Shitara from the National Cancer Center Hospital East, Japan, presented additional health-related quality of life (HRQoL) data from the landmark DESTINY-Gastric04 trial, further demonstrating the benefits of trastuzumab deruxtecan (T-DXd) in preserving patients' quality of life. During the meeting, Oncology Frontier interviewed Prof. Shitara to discuss the global significance of the study, China’s pivotal contribution, and the future direction of gastric cancer treatment.
Oncology Frontier:
With the successful completion of DESTINY-Gastric04, T-DXd has marked another major milestone in HER2-targeted therapy for advanced gastric cancer. As the global principal investigator, how do you view the significance of this study for gastric cancer treatment worldwide?
Prof. Kohei Shitara:
HER2-positive disease represents an important molecular subtype of gastric cancer, accounting for approximately 15% of all cases. For many years, the standard first-line treatment has been chemotherapy plus trastuzumab, with or without pembrolizumab. However, there had been no HER2-targeted therapy available in the second-line setting for more than a decade, with paclitaxel plus ramucirumab, established by the RAINBOW trial, serving as the standard of care.
As a next-generation HER2-targeted antibody-drug conjugate (ADC), T-DXd demonstrated promising antitumor activity from its first-in-human studies and subsequently became the standard treatment for third-line and later settings following the DESTINY-Gastric01 trial.
DESTINY-Gastric04 directly compared T-DXd with paclitaxel plus ramucirumab in terms of efficacy and safety. The study showed that T-DXd extended median overall survival (OS) by more than three months compared with the control arm, with a hazard ratio (HR) of 0.70. Significant improvements were also observed in objective response rate (ORR) and progression-free survival (PFS).
Importantly, this is the first randomized Phase III trial to demonstrate that second-line HER2-targeted therapy is superior to the long-standing standard regimen of paclitaxel plus ramucirumab, firmly establishing HER2-targeted therapy as the new standard of care for second-line treatment of HER2-positive advanced gastric cancer.
In addition, the HRQoL analysis presented at this year’s ASCO meeting showed that patients receiving T-DXd experienced a longer time to first deterioration (TTFD) across multiple quality-of-life domains compared with the control group.
- EQ-5D-5L Visual Analog Scale (VAS): 3.5 vs 3.0 months (HR=0.79; P=0.063)
- FACT-G total score: 3.5 vs 2.8 months (HR=0.74; P=0.015)
- Emotional Well-Being (EWB): 5.1 vs 3.7 months (HR=0.74; P=0.026)
- Social Well-Being (SWB): 3.8 vs 2.5 months (HR=0.71; P=0.006)
Across all FACT-Ga subscales, patients treated with T-DXd maintained stable quality-of-life scores without clinically meaningful deterioration. Furthermore, mixed model repeated measures (MMRM) analyses demonstrated significantly better outcomes for the T-DXd arm in the FACT-G total score, Functional Well-Being (FWB), and Social Well-Being (SWB) domains.
We are also continuing to investigate T-DXd in combination with chemotherapy and immune checkpoint inhibitors as a first-line treatment for HER2-positive advanced gastric cancer.
Oncology Frontier:
Approximately 20% of patients enrolled in DESTINY-Gastric04 were recruited from China, significantly accelerating trial completion. Looking back, how would you evaluate China’s contribution? More broadly, how has China’s progress in gastric cancer research influenced global treatment development?
Prof. Kohei Shitara:
First, I would like to sincerely thank the investigators, patients, and families in China for their tremendous contribution to this study. China enrolled more than 20% of all participants, providing critical support for the successful completion of the trial.
Notably, both Chinese and broader Asian patient subgroups demonstrated particularly favorable efficacy outcomes, which may have contributed to the study’s overall success.
Looking across the broader field of gastric cancer research, China is now playing a leading role in the development of innovative therapies. Beyond continued advances in HER2-targeted treatments, Chinese researchers have also achieved remarkable progress in emerging targets such as Claudin 18.2.
I have increasingly had opportunities to learn from Chinese investigators about innovative drug development. Several novel therapies developed in China are already being evaluated in global Phase III clinical trials, and I look forward to seeing these treatments redefine future standards of care for gastric cancer.
I have tremendous respect for and appreciation of the remarkable achievements made by Chinese investigators and pharmaceutical companies in advancing gastric cancer research.
Oncology Frontier:
Based on the Phase III evidence from DESTINY-Gastric04, China became the first country to approve T-DXd for second-line treatment of HER2-positive advanced gastric cancer, and subsequently incorporated it as a Category I recommendation (Level 1A evidence) in the 2026 CSCO Gastric Cancer Guidelines. How do you view China’s leadership in approving this indication ahead of other regions?
Prof. Kohei Shitara:
I was delighted to learn that the National Medical Products Administration (NMPA) approved T-DXd for second-line treatment of HER2-positive advanced gastric cancer based on the Phase III DESTINY-Gastric04 results.
Previously, T-DXd was available only as a third-line therapy, meaning that some patients unfortunately missed the opportunity to receive this highly effective treatment earlier in their disease course. Making T-DXd available in the second-line setting will allow many more patients in China to benefit from timely treatment and improved survival outcomes.
Once again, I would like to thank China for its substantial contribution to this study and for its forward-looking regulatory decision.
Today, T-DXd has also been approved for second-line HER2-positive advanced gastric cancer in the United States, European Union, Japan, and several other regions. China’s early approval significantly accelerated global access to this important therapy, and I greatly admire the efficiency and leadership demonstrated throughout this process.
Oncology Frontier:
As the global principal investigator of DESTINY-Gastric04, what message would you like to share following the approval of T-DXd for second-line HER2-positive advanced gastric cancer in China?
Prof. Kohei Shitara:
First, I would like to congratulate everyone involved on the successful completion of the DESTINY-Gastric04 study and on the approval of T-DXd for second-line HER2-positive advanced gastric cancer in China.
I would also like to once again thank the Chinese investigators, patients, and all collaborators for their invaluable support of this study and many other gastric cancer clinical trials.
I have already established several collaborations with colleagues in China, and I hope we can continue to strengthen our partnerships in the future. By learning from one another and jointly developing safer and more effective therapies, we can ultimately improve both survival and quality of life for patients with gastric cancer around the world.
Prof. Kohei Shitara
