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TOPAZ-1: What the Biliary Tract Cancer Trial Found
TOPAZ-1 added durvalumab to gemcitabine and cisplatin for advanced biliary tract cancer — the first phase 3 trial in more than a decade to improve on that chemotherapy. Two-year survival more than doubled, from a low base.
Original commentary from the Cancer Explained editorial team.
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Ten years without a better first treatment
Biliary tract cancer covers the bile ducts inside and outside the liver, and the gallbladder. It is uncommon, it is usually found late, and the outlook is poor.
The first treatment for advanced disease had been gemcitabine plus cisplatin for more than ten years. Not because it works well, but because nothing had beaten it. TOPAZ-1 is the phase 3 trial that finally did.
How the trial was run
| Field | Detail |
|---|---|
| Trial | TOPAZ-1 |
| Identifier | NCT03875235 |
| Phase | Phase 3 |
| Design | Randomised, double-blind, placebo-controlled |
| Cancer type | Previously untreated unresectable, metastatic or recurrent biliary tract cancer |
| Comparator | Durvalumab or placebo, with gemcitabine and cisplatin for up to eight cycles, then durvalumab or placebo alone |
| Primary objective | Overall survival |
685 people were randomised: 341 to durvalumab and 344 to placebo. After the chemotherapy phase, the immune drug or the placebo continued on its own until the cancer progressed or the side effects became unacceptable.
The survival result
By the data cutoff, 198 of the 341 people in the durvalumab group had died (58.1%), against 226 of 344 on placebo (65.7%).
The hazard ratio for death was 0.80 (95% CI 0.66 to 0.97, p=0.021) — about a 20% lower risk of dying at any given moment.
Progression-free survival also improved, with a hazard ratio of 0.75 (95% CI 0.63 to 0.89, p=0.001). Tumours shrank in 26.7% of the durvalumab group and 18.7% on placebo.
Two-year survival, and what it hints at
The figure that drew attention was survival at 24 months: an estimated 24.9% with durvalumab (95% CI 17.9 to 32.5) against 10.4% on placebo (95% CI 4.7 to 18.8).
More than double, in relative terms. Under a quarter, in absolute terms. Both readings are true and both matter.
Note also how wide those confidence intervals are — the placebo estimate runs from under 5% to nearly 19%. Few people remained in the analysis by that point, so the two-year figures are less certain than the hazard ratio.
The shape of that gap is the interesting part. A modest hazard ratio combined with a large difference at two years is the pattern you see when a minority of people get a long-lasting benefit rather than everyone getting a small one.
The side effects did not get gentler
Severe side effects — grade 3 or 4 — occurred in 75.7% of the durvalumab group and 77.8% of the placebo group.
Adding the immune drug did not make treatment harder to tolerate. Nor did it make it easier. Three-quarters of people in both arms had a severe event, which is a fact about gemcitabine and cisplatin, not about durvalumab.
What this does not mean
- It does not mean the outlook is now good. Fewer than a quarter of people were alive at two years even with the better regimen.
- It does not identify who benefits. The report does not name a test that predicts who gets the durable benefit hinted at by the two-year figures.
- The published report does not give a median survival figure, so none is quoted here.
- It says nothing about earlier-stage biliary tract cancer, or about people who have already had treatment. Everyone here was untreated with inoperable, metastatic or recurrent disease.
Questions at a biliary tract cancer diagnosis
- Where exactly is the cancer — bile duct, gallbladder, inside or outside the liver?
- Has my tumour been tested for changes that other targeted drugs act on?
- If chemotherapy is this demanding, what would make us stop or pause?
Sources
This article was written from the sources below, which were checked on the source-check date shown above.
- NEJM Evidence: Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer (TOPAZ-1) (primary)
How this article was prepared
Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.
Cancer Explained is published by the National Cancer Information Foundation as a nonprofit-oriented public-interest education project. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.
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Put the story in context
Prevention, possible warning signs, screening, and diagnosis
This story relates to Biliary tract cancer. The information below is general: it does not reveal anything else about a public person’s health, and not every point applies to every cancer. Personal advice depends on age, symptoms, family history, exposures, and medical history.
Prevention and risk reduction
Not every cancer can be prevented. Avoiding tobacco, protecting skin from ultraviolet radiation, limiting alcohol, staying active, and receiving recommended HPV or hepatitis B vaccination can lower the risk of certain cancers. A risk factor is not a prediction or a cause in one individual.
Symptoms and possible early signs
Possible signs vary and are often caused by conditions other than cancer. Changes worth discussing include a new lump, unexplained bleeding or weight loss, a persistent cough, lasting bowel or bladder changes, a changing skin spot, or symptoms that persist or worsen. Some early cancers cause no symptoms.
Screening and early detection
Screening looks for certain cancers before symptoms begin. Recommended tests exist only for some cancers and depend on age and risk. Screening can have benefits and harms; it is not the same as evaluating a new symptom, and there is no single routine scan or blood test that reliably screens for every cancer.
How cancer is diagnosed
Diagnosis may involve a history and exam, imaging, laboratory tests, and often a biopsy. Pathology can identify the cancer type and may test biomarkers that guide treatment. Symptoms, screening results, tumor markers, or online stories alone cannot confirm cancer.
Learn about this story’s cancer topic
A public story may encourage questions, but it should not be used to estimate your risk or choose testing. Contact a healthcare professional about a persistent or concerning change. Seek urgent care for severe or rapidly worsening symptoms.