Japan has approved durvalumab monotherapy and durvalumab plus tremelimumab for unresectable hepatocellular carcinoma, durvalumab plus tremelimumab and chemotherapy for unresectable, advanced, or recurrent non–small cell lung cancer, and durvalumab plus chemotherapy for curatively unresectable biliary tract cancer.
Japan’s Ministry of Health, Labor, and Welfare has approved durvalumab (Imfinzi) plus tremelimumab (Imjudo) for adults with unresectable hepatocellular carcinoma (HCC) and unresectable, advanced, or recurrent non–small cell lung cancer (NSCLC) in combination with chemotherapy.1
The agency also approved durvalumab monotherapy for adults unresectable HCC and in combination with chemotherapy for adults with curatively unresectable biliary tract cancer. The approvals are based on data from the phase 3 HIMALAYA (NCT03298451), POSEIDON (NCT03164616), and TOPAZ-1 (NCT03875235) trials.
“Japan has one of the highest rates of diagnosis for liver and biliary tract cancers in the world, and lung cancer remains the country’s leading cause of cancer death,” Dave Fredrickson, executive vice president for AstraZeneca’s oncology business unit, said in a news release. “With these approvals for durvalumab and tremelimumab, patients in Japan can now be treated with novel immunotherapy-based treatment regimens that have demonstrated significant survival benefits across three complex cancers with poor prognoses.”
In the HIMALAYA trial (n = 1171), investigators randomly assigned patients with unresectable HCC to 1 of 3 treatment arms: 300 mg of tremelimumab plus 1500 mg of durvalumab every 4 weeks (STRIDE regimen; n = 393); durvalumab monotherapy at 1500 mg every 4 weeks (n = 389); and sorafenib (Nexavar) monotherapy at 400 mg every day (n = 389).
Investigators reported a 22% reduction in risk for death in the STRIDE regimen arm compared with sorafenib (HR, 0.78; 95% CI, 0.66-0.92; P = .0035).2 Further results showed after 3 years, 31% of patients were alive in this experimental arm vs 20% of those treated with sorafenib.
The median OS in the STRIDE regimen group was 16.4 months compared with 13.8 months in the sorafenib group (HR, 0.78; 95% CI, 0.65-0.92; P = .0035). The 36-month OS rate it was 30.7% with the combination vs 20.2% with sorafenib group.
The median OS for the durvalumab monotherapy group was 16.6 months vs 13.8 months for the sorafenib group (HR, 0.86; 95% CI, 0.73-1.03). At 36 months it was 24.7% with durvalumab vs 20.2% with sorafenib.
In October 2022, the FDA approved durvalumab/tremelimumab for unresectable HCC based on the HIMALAYA data.3 The European Medicines Agency’s Committee for Medicinal Products for Human Use gave a positive opinion on the use of the combination to treat advanced lung and liver cancers in December 2022.4
In TOPAZ-1, investigators randomly assigned adults with locally advanced or metastatic biliary tract cancer to durvalumab plus gemcitabine and cisplatin for up to 8 cycles, followed by durvalumab every 4 weeks (n = 341) or placebo plus the same chemotherapy regimen followed by placebo every 4 weeks (n = 344).5
Durvalumab plus chemotherapy induced a median OS of 12.8 months (95% CI, 11.1-14.0) compared with 11.5 months (95% CI, 10.1-12.5) with chemotherapy alone (HR, 0.80; 95% CI, 0.66-0.97; P = .021). The median PFS was 7.2 months (95% CI, 6.7-7.4) with durvalumab plus chemotherapy vs 5.7 months (95% CI, 5.6-6.7) with chemotherapy alone (HR, 0.75; 95% CI, 0.63-0.89; P = .001).
The FDA approved the durvalumab/chemotherapy combination for this indication in September 2022, based on data from TOPAZ-1.6
Data from POSEIDON (N = 675) supported the use of durvalumab plus tremelimumab and chemotherapy for patients with unresectable, advanced or recurrent NSCLC. Investigators reported a median progression-free survival (PFS) of 5.5 months with the triplet regimen vs 4.8 months with chemotherapy.
Investigators also observed statistically significant and meaningful improvement in overall survival (OS) in the treatment arm (HR, 0.77; 95% CI, 0.65, 0.92; 2-sided P value = .00304). The median OS in the tremelimumab plus durvalumab arm was 14 months (95% CI, 11.7-16.1) vs in the chemotherapy arm it was 11.7 months (95% CI, 10.5-13.1).7
In November 2022, the FDA approved the triplet for adult patients with metastatic NSCLC with no sensitizing EGFR mutation or ALK genomic tumor aberrations.