January 18, 2022: “Positive results from the TOPAZ-1 Phase III trial showed AstraZeneca’s Imfinzi (durvalumab), in combination with standard-of-care chemotherapy, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) versus chemotherapy alone as a 1st-line treatment for patients with advanced biliary tract cancer (BTC).
These results will be presented on 21 January at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder.
Approximately 50,000 people in the US, Europe and Japan and about 210,000 people worldwide are diagnosed with BTC each year.
These patients have a poor prognosis, with approximately 5% to 15% of all patients with BTC surviving five years.
Do-Youn Oh, MD, PhD, Professor, Division of Medical Oncology, Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, and principal investigator in the TOPAZ-1 Phase III trial, said: “After minimal progress for more than a decade in advanced biliary tract cancer, the TOPAZ-1 results are a tremendous advance for our patients, showing a clear survival benefit for Imfinzi added to chemotherapy compared to standard of care with a remarkable safety profile.
This combination will provide a desperately needed and potentially practice-changing new treatment option in a setting where the current prognosis is devastating.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The results from the TOPAZ-1 trial challenge treatment expectations in advanced biliary tract cancer and provide compelling evidence that longer-term survival is possible.
Overall survival improves over time with an estimated one in four patients on Imfinzi plus chemotherapy alive at two years compared to one in ten on chemotherapy alone.
This is a potential new standard of care for patients in this setting and we remain committed to making advances in gastrointestinal cancers with high unmet need.”
In a predefined interim analysis, patients treated with Imfinzi in combination with standard-of-care chemotherapy experienced a 20% reduction in the risk of death versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI], 0.66-0.97; 2-sided p=0.021). Median OS was 12.8 months versus 11.5 for chemotherapy.
An estimated 25% of patients were still alive at two years versus 10% for chemotherapy.
Results also showed a 25% reduction in the risk of disease progression or death with Imfinzi plus chemotherapy (HR, 0.75; 95% CI, 0.64-0.89; 2-sided p=0.001). Median PFS was 7.2 months for the combination versus 5.7 for chemotherapy.
Patients treated with Imfinzi plus chemotherapy achieved an objective response rate (ORR) of 26.7% versus an ORR of 18.7% for patients treated with chemotherapy alone.
Summary of efficacy resultsi:
| Imfinzi + chemotherapy(n=341) | Placebo + chemotherapy(n=344) | |
| OSii,iii | ||
| Percentage of patients with event | 58.1 | 65.7 |
| Median OS (95% CI) (in months) | 12.8 (11.1, 14.0) | 11.5 (10.1, 12.5) |
| HR (95% CI)2-sided p-value | 0.80 (0.66, 0.97)0.021 | |
| OS rate at 18 months (95% CI) (%) | 35.1 (29.1, 41.2) | 25.6 (19.9, 31.7) |
| OS rate at 24 months (95% CI) (%) | 24.9 (17.9, 32.5) | 10.4 (4.7, 18.8) |
| PFSiv,v | ||
| Percentage of patients with event | 80.9 | 86.3 |
| Median PFS (95% CI) (in months) | 7.2 (6.7, 7.4) | 5.7 (5.6, 6.7) |
| HR (95% CI)2-sided p-value | 0.75 (0.64, 0.89)0.001 | |
| ORR (%) | 26.7 | 18.7 |
i. Analysis was done at 62% maturity in OS data.
ii. Investigator-assessed OS data cut-off date was 11 August 2021.
iii. Median follow-up in censored patients at DCO: 13.7 months (range 0.4-27.2) for Imfinzi plus chemotherapy, 12.6 months (range 0.7-26.0) for chemotherapy alone.
iv. Investigator-assessed PFS data cut-off date was 11 August 2021.
v. Median follow-up in censored patients at DCO: 9.2 months (range 0.0-24.0) for Imfinzi plus chemotherapy, 6.9 months (range 0.0-20.4) for chemotherapy alone.
Imfinzi plus chemotherapy did not increase the discontinuation rate due to adverse events (AEs) compared to chemotherapy alone.
Grade 3 or 4 treatment-related AEs were experienced by 62.7% of patients treated with Imfinzi and chemotherapy, and by 64.9% of patients receiving chemotherapy alone.
Treatment-related AEs led to discontinuation in 8.9% of patients treated with the Imfinzi combination versus 11.4% of patients receiving chemotherapy.
In December 2020, Imfinzi was granted Orphan Drug Designation in the US for the treatment of BTC.
In October 2021, an Independent Data Monitoring Committee recommended the TOPAZ-1 Phase III trial to be unblinded at an interim analysis due to clear evidence of efficacy for Imfinzi plus chemotherapy.
An additional presentation featured during the ASCO Gastrointestinal Cancers Symposium will showcase Imfinzi data from the HIMALAYA Phase III trial, demonstrating the potential of this medicine in the treatment of unresectable liver cancer.”
