Updated data from the HIMALAYA and NIAGARA trials presented at the 2024 European Society for Medical Oncology (ESMO) Congress demonstrate that durvalumab-based regimens significantly improve overall survival (OS) and event-free survival (EFS) in patients with unresectable hepatocellular carcinoma (HCC) and muscle-invasive bladder cancer (MIBC). These findings highlight the potential of durvalumab in addressing critical unmet needs in these challenging cancers.
Durvalumab Plus Tremelimumab in Hepatocellular Carcinoma
The Phase 3 HIMALAYA trial (NCT03298451) evaluated durvalumab (Imfinzi; AstraZeneca) in combination with tremelimumab-actl (Imjudo; AstraZeneca) in patients with unresectable HCC who had not received prior systemic therapy and were ineligible for localized treatment. The study excluded patients with hepatic encephalopathy, clinically meaningful ascites, active gastrointestinal bleeding, or hepatitis B and C virus co-infection.
The combination, known as the STRIDE regimen, demonstrated a sustained and clinically meaningful OS benefit at 5 years. The STRIDE regimen reduced the risk of death by 24% compared with sorafenib (Nexavar; Bayer HealthCare). At 5 years, 19.6% of patients treated with STRIDE were alive compared to 9.4% of those treated with sorafenib. The median duration of follow-up for OS was 62.5 months in the STRIDE group and 59.9 months in the sorafenib group.
The safety profile of the STRIDE regimen was consistent with the known profiles of the individual drugs, with no new safety signals observed with longer follow-up. Serious adverse events occurred in 17.5% of patients treated with STRIDE compared to 9.9% with sorafenib.
Durvalumab with Chemotherapy in Bladder Cancer
The NIAGARA study (NCT03732677) investigated durvalumab with chemotherapy in patients with resectable MIBC (clinical stage T2-T4aN0/1M0) undergoing radical cystectomy who had not received prior systemic chemotherapy or immunotherapy for MIBC. Patients with lymph node or metastatic disease, prior pelvic radiotherapy, or recent use of immunosuppressive medication were excluded.
Durvalumab with chemotherapy showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death compared to neoadjuvant chemotherapy alone. The median EFS was not reached for the durvalumab arm but was 46.1 months for the comparator arm. An estimated 67.8% of patients treated with durvalumab were event-free at 2 years compared to 59.8% for the comparator.
Regarding OS, durvalumab reduced the risk of death by 25% compared to neoadjuvant chemotherapy with radical cystectomy. The median survival was not reached for either arm; however, 82.2% of patients treated with durvalumab were alive at 2 years compared to 75.2% in the comparator arm.
