survival vs. sorafenib in patients with unresectable liver cancer regardless of baseline liver functional reserve
TOPAZ-1 Phase III trial subgroup analysis showed the addition of IMFINZI to standard-of-care chemotherapy improved overall survival benefit in patients with advanced biliary tract cancer regardless of primary tumor location
WILMINGTON, Del.–(BUSINESS WIRE)– AstraZeneca presented data for IMFINZI® (durvalumab) combinations from the HIMALAYA and TOPAZ-1 Phase III trials at the European Association for the Study of the Liver’s International Liver Congress 2022 (EASL 2022) and the European Society for Medical Oncology’s World Congress on Gastrointestinal Cancer (ESMO World GI 2022).
Exploratory sub-analyses from HIMALAYA and TOPAZ-1 were presented at ESMO World GI 2022, June 29 to July 2 in Barcelona. Additionally, health-related quality-of-life data from HIMALAYA were presented at EASL 2022, June 22 to 26 in London.
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “The HIMALAYA results show a consistent survival benefit with the STRIDE regimen in patients with unresectable liver cancer regardless of baseline liver functional reserve, and TOPAZ-1 data show that IMFINZI plus chemotherapy improved outcomes for biliary tract cancer patients regardless of where their tumor was located or where they lived. These important subgroup analyses add to the body of evidence demonstrating the potential for IMFINZI combinations to meaningfully improve outcomes for these patients who are in need of effective and generally well tolerated treatments.”
HIMALAYA Phase III analyses in unresectable liver cancer at ESMO World GI 2022 and EASL 2022
An exploratory sub-analysis from the HIMALAYA Phase III trial evaluated the efficacy and safety of the STRIDE regimen (single tremelimumab regular interval durvalumab) or durvalumab monotherapy versus sorafenib by baseline liver function, and liver function over time in patients with unresectable liver cancer. Liver function was determined using the ALBI (albumin-bilirubin) scoring system, a model for assessing the severity of liver dysfunction that describes worsening severity across three grades (ALBI grades 1 through 3).
Patients with liver cancer tend to have underlying liver cirrhosis, leading to impaired liver function and poor prognosis.1 Systemic therapies for advanced liver cancer have the potential to exacerbate pre-existing liver disease and increase the risk of liver-related adverse events. Data presented at ESMO World GI 2022 showed that the STRIDE regimen improved survival regardless of liver function scores at baseline, with overall survival (OS) hazard ratios (HR) that were generally consistent with the primary analysis in both the ALBI grade 1 subgroup (HR 0.79; 95% confidence interval [CI] 0.62-1.01) and ALBI grade 2/3 subgroup (HR 0.83; 95% CI 0.65-1.05).2 The overall response rate, duration of response and tolerability profile for STRIDE were consistent regardless of ALBI score.2 Further, liver function was stable over time for patients treated with STRIDE who remained on the trial.
An additional analysis from the HIMALAYA trial was conducted using a self-reported questionnaire to assess the impact of treatment and treatment status on health-related quality-of-life in patients with unresectable liver cancer. Results presented at EASL 2022 demonstrated that patients treated with the STRIDE regimen had better quality-of-life than those treated with sorafenib, with fewer patients experiencing moderate to severe problems in domains including mobility, self-care, pain/discomfort and anxiety/depression.3 Further, treatment discontinuation was associated with a larger magnitude of worsening health status than disease progression. Following discontinuation, more patients reported experiencing moderate to extreme problems on all domains.3 These results highlight the impact of treatment discontinuation and the potential quality-of-life benefits for maintaining patients on treatment with the STRIDE regimen.
Primary results from the HIMALAYA Phase III trial were presented during the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium in January 2022 and published in New England Journal of Medicine (NEJM) Evidence in June 2022. The trial met its primary endpoint demonstrating a statistically significant improvement of OS with a single priming dose of tremelimumab plus durvalumab every four weeks versus sorafenib.4 The safety profiles of the STRIDE regimen and for durvalumab alone were consistent with the known profiles of each medicine, and no new safety signals were identified.4
TOPAZ-1 Phase III trial subgroup analysis in advanced biliary tract cancer at ESMO World GI 2022
An exploratory subgroup analysis of patients enrolled in the TOPAZ-1 Phase III trial evaluated the efficacy and safety of durvalumab plus standard-of-care chemotherapy (gemcitabine plus cisplatin) compared to placebo plus chemotherapy by primary tumor location, including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer.
The analysis showed a consistent OS benefit for patients treated with durvalumab and chemotherapy (gemcitabine plus cisplatin) compared to chemotherapy alone across all primary tumor locations, with an improved OS with durvalumab: intrahepatic cholangiocarcinoma (HR 0.76; 95% CI 0.58-0.98), extrahepatic cholangiocarcinoma (HR 0.76; 95% CI 0.49-1.19) and gallbladder cancer (HR 0.94; 95% CI 0.65-1.37).5 This consistent OS benefit was observed regardless of geographic location, with patients in North America, Europe and Asia all showing benefit. The incidence of grade 3 or 4 adverse events and treatment-related adverse events were generally comparable among treatment groups, irrespective of primary tumor locations.
Primary results from the TOPAZ-1 trial were presented during the ASCO GI Symposium in January 2022 and published in NEJM Evidence in June 2022. Durvalumab in combination with standard-of-care chemotherapy demonstrated a statistically significant and clinically meaningful OS benefit versus chemotherapy alone, meeting the primary endpoint.6 Durvalumab plus chemotherapy did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.6