There overall survival of patients with advanced biliary tract cancer improves with a AstraZeneca’s immunotherapy-durvalumab combination plus standard-of-care chemotherapy – with a clinically significant and long-lasting overall survival benefit. These are the updated results of the Phase 3 Topaz1 study, the first to highlight this improvement, presented today at the European Society for Medical Oncology (Esmo) Congress in Paris. The pharmaceutical company announced it in a note.
Updated data of durvalumab in combination with chemotherapy (gemcitabine plus cisplatin) showed greater clinical efficacy at the extended follow-up of 6.5 months, showing a 24% reduction in the risk of death compared to chemotherapy alone. In fact, the updated median overall survival was 12.9 months, compared with 11.3 with chemotherapy alone. The number of patients alive at 2 years is estimated to have more than doubled compared to chemotherapy alone (23.6% versus 11.5%). Results were observed in all predefined subgroups, regardless of tumor location and tumor surface protein PD-L1 expression. Furthermore, the overall survival benefit was observed in both patients with stable disease and in patients whose cancer has shrunk or disappeared (responders).
The safety profile of durvalumab plus chemotherapy continued to be well tolerated with no new safety signals observed at extended follow-up. Treatment-related grade 3 or 4 adverse events were seen in 60.9% of patients treated with durvalumab and chemotherapy and in 63.5% of those treated with chemotherapy alone. Durvalumab plus chemotherapy did not increase the discontinuation rate for AEs compared to chemotherapy alone (8.9% for durvalumab versus 11.4% for chemotherapy).
“Biliary tract cancer is a constantly growing disease. Every year in Italy there are about 5,400 new cases – he says Lorenzo Antonuzzo, associate professor of medical oncology at the University of Florence and director of Sodc Clinical Oncology Aou Careggi, Florence – There are no screening tests or diagnostic tests capable of identifying this neoplasm at an early stage, when surgical removal is still possible. The disease is often characterized by generic symptoms (e.g. abdominal pain, weight loss, nausea, malaise), which can be easily underestimated or confused with those of other conditions. For this reason, 70% of patients present at diagnosis with a disease already in an advanced stage, with little possibility of treatment. Hence the strong clinical need for new therapies “.
For the specialist “it is exciting to observe the improved overall survival achieved by combining durvalumab plus chemotherapy versus standard of care for patients with advanced biliary tract cancer, at a median follow-up of nearly 2 years. With limited therapeutic advances over the past 10 years, these patients have long faced a poor prognosis. For the first time, a combination of immunotherapy has shown the ability to modify the treatment of this disease and should become the new standard of care. “
Esmo was also presented with an exploratory analysis of the Himalaya phase 3 study to evaluate the impact of disease causes on outcomes for patients with unresectable hepatocellular carcinoma. The data suggests a trend towards improved overall survival compared to sorafenib with the ‘Stride’ regimen (single priming dose of tremelimumab, an anti-Ctla4 antibody, in addition to durvalumab), regardless of the cause of disease (hepatitis B virus Hbv, hepatitis C virus Hcv, non-viral origin). Similar trends were observed with durvalumab versus sorafenib across all subgroups.
“These long-term data – he declares Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca – support the survival benefit and well tolerated safety profile of durvalumab as an adjunct to standard chemotherapy in patients with advanced biliary tract cancer. With these results, the data from the exploratory analysis of the Himalaya study and the recent approval by the “American” FDA based on the Topaz1 study, we continue our commitment with the aim of prolonging the survival of patients with gastrointestinal tumors who have strong need for new therapeutic options “.
In 2021 – recalls AstraZeneca – the positive results of the Himalaya phase 3 study showed that the Stride regimen produced a clinically and statistically significant improvement in overall survival compared to sorafenib as first-line treatment of patients with unresectable, untreated hepatocellular carcinoma previously with systemic therapies and not eligible for localized treatment. When subgroups were balanced according to prognostic factors, compared to sorafenib, Hbv patients treated with the Stride regimen showed a 36% reduction in the risk of death and a mean duration of response of 25.69 months (versus 17 sorafenib). In patients with Hcv the reduction in the risk of death was 11% and the mean duration of response was 13.5 (15.7 months with sorafenib). In patients with non-viral etiology, the reduction in the risk of death was 23%. The mean duration of response was 13.21 (6.01 months with sorafenib).
Himalaya is the only Phase 3 study demonstrating a survival benefit with immunotherapy in patients with unresectable non-viral hepatocellular carcinoma (disease associated with non-viral causes including liver disease, obesity and diabetes), the note highlights. Based on these results, the Stride regimen is being evaluated by regulatory authorities for use in this form of cancer whose prevalence has significantly increased over the past twenty years.
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