The European Union has approved durvalumab plus tremelimumab-actl for first-line treatment of advanced or unresectable hepatocellular carcinoma and in combination with platinum-based chemotherapy in metastatic non–small cell lung cancer, according to a news release from AstraZeneca.
The European Union (EU) has approved durvalumab (Imfinzi) plus tremelimumab-actl (Imjudo) for first-line treatment of advanced or unresectable hepatocellular carcinoma (HCC) and in combination with platinum-based chemotherapy in metastatic non–small cell lung cancer (NSCLC), according to a news release from AstraZeneca.1
The European Medicines Agency’s Committee for Medicinal Products for Human Use issued a favorable recommendation for the combination in these indications in December 2022. The regulatory decision is based on positive results from the phase 3 HIMALAYA trial (NCT03298451) in HCC and the phase 3 POSEIDON trial (NCT03164616) in NSCLC.
“Lung cancer is one of the most prevalent and deadly cancers in Europe, and rates of liver cancer are rising steadily across the region,” Dave Fredrickson, executive vice president of AstraZeneca’s oncology business unit, said in a news release. “These approvals for durvalumab and plus tremelimumab bring critically needed, novel immunotherapy-based treatment regimens that will potentially deliver life-extending benefits for European patients with advanced liver and non-small cell lung cancers.”
In HIMALAYA, 393 patients were randomly assigned to the STRIDE regimen (1 dose of 300 mg tremelimumab and 1500 mg durvalumab every 4 weeks), 389 to durvalumab monotherapy at the same dose and schedule, 389 to twice-daily 400 mg sorafenib (Nexavar), or 153 to 75 mg tremelimumab every 4 weeks for 4 doses plus durvalumab given every 4 weeks (T75+D). The T75+D arm has since closed.
The open-label, multicenter, global, phase 3 trial enrolled patients with confirmed unresectable HCC who had an ECOG performance status of 0 or 1 and Child-Pugh A disease. Patients could not have previously received systemic therapy or have main portal vein thrombosis.
The STRIDE regimen induced a 22% reduction in risk for death compared with sorafenib (HR, 0.78; 96.02% CI, 0.65-0.93; P = .0035).2 The median overall survival (OS) in the investigative arm was 16.4 months (95% CI, 14.2-19.6) vs 13.8 months (95% CI, 12.3-16.1) in the control arm, meeting the primary end point of the research.
Findings presented at the 2022 ESMO World Congress on Gastrointestinal Cancer in June showed that STRIDE elicited a median OS of 23.43 months (95% CI, 19.19-28.75) compared with 19.02 months (95% CI, 15.67-23.16) for sorafenib (HR, 0.79; 95% CI, 0.62-1.01) in patients with a baseline albumin-bilirubin (ALBI) grade of 1. In patients with ALBI grade 2/3, the STRIDE regimen produced a median OS of 11.30 months (95% CI, 9.33-14.19) vs 9.72 months (95% CI, 7.23-11.76) for sorafenib (HR, 0.83; 95% CI, 0.65-1.05).3
“This approval in Europe is welcome news for eligible patients with advanced liver cancer, who face a poor prognosis and are in need of well-tolerated treatments that can meaningfully extend overall survival,” HIMALAYA investigator Bruno Sangro, MD, PhD, director of the liver unit and professor of internal medicine at Clínica Universidad de Navarra in Spain, said in a news release. “In HIMALAYA, an estimated 31% of patients treated with this novel combination of tremelimumab with durvalumab were alive at three years, while only 20% of patients treated with sorafenib were still alive at the same duration of follow-up.”
In POSEIDON, 338 patients with metastatic NSCLC without sensitizing EGFR mutation or ALK aberrations were assigned to tremelimumab at 75 mg or 1 mg/kg in those <30 kg plus 1500 mg durvalumab and platinum-based chemotherapy every 3 weeks for 4 cycles. That was followed by 1500 mg durvalumab monotherapy every 4 weeks, then investigators administered a fifth dose of tremelimumab at 75 mg at week 16 in combination with the sixth dose of durvalumab. Another 337 patients were assigned to platinum-based chemotherapy. Treatment continued until progressive disease or intolerable toxicity.
In findings presented at the 2022 ESMO Congress, the tremelimumab/ durvalumab/chemotherapy combination significantly improved OS vs chemotherapy alone (14 vs 11.7 months; HR, 0.77; 95% CI, 0.65-0.92; 2-sided P = .00304). This translated to a 23% reduction in the risk for death. At 3 years, an estimated 25% of patients assigned to the combination were alive compared with 13.6% in the chemotherapy alone arm.4
The FDA approved the tremelimumab/durvalumab/chemotherapy combination for this patient population in November 2022.5
“Patients with metastatic non-small cell lung cancer continue to need new therapies that can meaningfully extend survival, including for many patients whose disease does not respond to current therapies,” lead POSEIDON investigator Solange Peters, MD, PhD, head of the medical oncology service and chair of Thoracic Oncology at Hospitalier Universitaire Vaudois in Lausanne, Switzerland, said in a news release. “The approval of tremelimumab added to durvalumab and chemotherapy means that patients in Europe with this devastating cancer now have a valuable new treatment approach with demonstrated long-term survival benefits.”