AstraZeneca Announces Positive Phase III Results for Imfinzi-Based Combination Therapies in Biliary Tract Cancer and Hepatocellular Carcinoma

Source: PharmaCube Info

Author: Shi Bei

On January 18, AstraZeneca announced positive results from the Phase III TOPAZ-1 study of the anti-PD-L1 monoclonal antibody Imfinzi (durvalumab) in combination with standard-of-care chemotherapy for the first-line treatment of advanced biliary tract cancer (BTC). Compared to chemotherapy alone (gemcitabine + cisplatin), BTC patients showed statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS).

TOPAZ-1 Study is the first Phase III trial to demonstrate improved survival with an immunotherapy-based combination in the first-line treatment of advanced biliary tract cancer. Furthermore, the combination did not increase the risk of treatment discontinuation due to adverse events compared to chemotherapy alone. These results will be presented on January 21, 2022, at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

In the pre-planned interim analysis, compared with chemotherapy alone, the Imfinzi plus chemotherapy group reduced the risk of patient death by 20% ([HR]: 0.80; 95% [CI], 0.66-0.97; two-sided p=0.021), with a median OS of 12.8 months, while the chemotherapy group had 11.5 months. Approximately 25% of patients in the combination chemotherapy group were still alive after two years, compared with 10% in the chemotherapy group.

Moreover, the combination of Imfinzi and chemotherapy reduced the risk of disease progression or death by 25% (HR, 0.75; 95% CI, 0.64-0.89; two-sided p=0.001). The median PFS was 7.2 months in the combination therapy group compared to 5.7 months in the chemotherapy group. The objective response rate (ORR) was 26.7% in the combination therapy group versus 18.7% in patients receiving chemotherapy alone.

On the same day, AstraZeneca announced positive results from another Phase III HIMALAYA study of Imfinzi. This study aimed to evaluate the efficacy of Imfinzi in combination with the anti-CTLA-4 antibody tremelimumab as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were unsuitable for local treatment.

Compared with Sorafenib, the overall survival (OS) of patients in the Imfinzi combined with tremelimumab group showed statistically significant and clinically meaningful improvement. The risk of death for patients was reduced by 22% ([HR]: 0.78, 96.02% [CI] 0.65-0.93; p=0.0035). The median OS in the combination therapy group was 16.4 months, compared to 13.8 months in the Sorafenib group. It was estimated that 31% of patients in the combination therapy group were still alive after three years, compared to 20% in the Sorafenib group.

In terms of safety, compared with sorafenib, the combination therapy also did not increase severe hepatotoxicity, and there were fewer discontinuations due to treatment-related adverse events.

Note: The original text has been abridged.