China's HER2-ADC Regimen Beats Chemo in NEJM Trial

 

China's HER2-ADC Regimen Beats Chemo in NEJM Trial

Urothelial carcinoma — cancer of the bladder, renal pelvis, and ureter — is one of the most common cancers of the urinary system. In 2022 alone, China recorded 92,900 new cases and more than 40,000 deaths, with men far more affected than women and risk rising sharply after age 40.

For nearly 50 years, cisplatin-based chemotherapy has been the default first-line treatment for locally advanced or metastatic disease. But it comes with a real cost: median survival of only 14–15 months, and toxicity so severe that many patients — especially those with kidney problems or poor overall health — simply can't tolerate it. Doctors have long needed something better. Now they may have it.

A Chinese-Led Study Breaks Into NEJM

The RC48-C016 trial, led by Prof. Jun Guo of Peking University Cancer Hospital and conducted by Prof. Xinan Sheng's team across 74 centers in China, is the first Phase III randomized trial to prove — head-to-head — that an immunotherapy + ADC (antibody-drug conjugate) combination beats standard platinum chemotherapy in first-line treatment of HER2-expressing urothelial carcinoma.

The study enrolled 484 patients with HER2-expressing (IHC 1+/2+/3+) advanced urothelial carcinoma, randomly assigned to either:

• Disitamab vedotin + toripalimab (the combination arm), or
• Standard chemotherapy (the control arm)

Results were published in the New England Journal of Medicine in October 2025 and presented at the ESMO Congress Presidential Symposium — the first original research from China's urologic oncology field to appear in NEJM.

The Results

Outcome	Combination Therapy	Chemotherapy
Median PFS	13.1 months	6.5 months
Median OS	31.5 months	16.9 months
Objective Response Rate	76.1%	—
Grade ≥3 Adverse Events	55.1%	86.9%

The combination therapy cut the risk of disease progression or death by 64% and the risk of death by 46%, while causing far fewer severe side effects. Benefits held steady across HER2 expression levels, cisplatin tolerance, and tumor location — meaning it works broadly, not just in a narrow subgroup.

A Decade in the Making

This result didn't come from nowhere. Prof. Sheng traced the program back to 2015, when the first study in this series began. Since then, Chinese researchers have steadily built a complete body of evidence — moving from later-line to first-line use, and from single-agent to combination therapy. Along the way, they also established the world's first HER2 testing standard specific to urothelial carcinoma, a standard now validated by studies in Europe and the U.S.

Prof. Ruiping Xiao, Deputy Editor of NEJM and Founding Dean of the Peking University Academy for Advanced Interdisciplinary Studies, called the study a milestone — proof that Chinese clinical research has made the leap from "more studies" to "better studies," earning genuine international recognition.

Now Approved for Patients

In April 2026, China's National Medical Products Administration (NMPA) approved the disitamab vedotin + toripalimab combination as first-line treatment for HER2-expressing (IHC 1+/2+/3+) locally advanced or metastatic urothelial carcinoma.

This matters because:

• It covers about 82.6% of HER2-expressing patients
• It works regardless of HER2 expression level or cisplatin eligibility
• It's the world's first approved HER2-ADC + immunotherapy combination for advanced urothelial carcinoma
• It's the first domestically developed "immunotherapy + ADC" combination therapy to reach market

The Bottom Line

For decades, patients with advanced urothelial carcinoma had one real option: chemotherapy, with all its risks and limits. The RC48-C016 trial suggests that's changing — offering a treatment that's not only more effective, but easier on the body. It's a rare case where a homegrown Chinese therapy has set a new global standard of care.

This article is based on clinical trial data and conference proceedings. It is intended for informational purposes and is not a substitute for medical advice. Patients should consult their oncologist regarding treatment options.