Background: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. Patients and methods: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). Results: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. Conclusions: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.
B, S., S L, C., R K, K., G, L., M, K., W, S., M, Y., E N, D. T., J, F., Y K, K., P R, G., L, R., A, H., V C, T., T, V. D., S C, T., V, B., Y, O., M, R., M, M., M J, P., C, G., J F, K., A, N., G K, A., Azevedo, S., Ignez Braghiroli, M., Girotto, G., Bragagnoli, A., Branco, R., Faccio, A., Moretto, A., Skare, N., Dutra, J., Viola, L., Vianna, K., Meton, F., Sette, C., Faulhaber, A., Tam, V. C., Couture, F., Biagi, J., Castel, H., Mulder, K., Ko, Y., Zbuk, K., Welch, S., Beaudoin, A., Heurgué, A., Assenat, E., Archambeaud, I., Tougeron, D., Peron, J., Gilabert, M., Bronowicki, J., Cattan, S., Blanc, J., Bouattour, M., Phelip, J., Boige, V., Michel, P., Frin, A., De Toni, E. N., Berres, M., Vogel, A., Berg, T., Ettrich, T., Waldschmidt, D., Heinrich Wedemeyer, H., Worns, M., Bitzer, M., Weiss, K., Lau, G., Chan, S. L., Yau, T., Ping Tai, Y., Shing Lee, A., Chiradoni Thungappa, S., Lokesh, K. N., Sureshchand Ostwal, V., Kiran Ashok, K., Mittal, S., Goyal, H., Srinivasan, S., Biswas, G., Mohan, M., Limaye, S., Asarawala, N., Rimassa, L., Falcone, A., Gianni, L., Gasbarrini, A., Daniele, B., Avallone, A., Luca Paolo Frassineti, G., Roila, F., Kudo, M., Kawaoka, T., Morimoto, M., Takikawa, Y., Kato, N., Yamashita, T., Osaki, Y., Motomura, K., Tateishi, R., Ohkawa, K., Wada, Y., Onishi, H., Sasahira, N., Inaba, Y., Kurosaki, M., Tsuji, K., Takei, Y., Aramaki, T., Hagihara, A., Furuse, J., Kioka, K., Koga, H., Sasaki, Y., Numata, K., Tada, T., Kawaguchi, Y., Nadano, S., Vasilyev, A., Breder, V., Lipatov, O., Dvorkin, M., Zarubenkov, O., Kutukova, S., Ponomarev, R., Shostka, K., Alyasova, A., Topuzov, E., Severtsev, A., Petrov, Y., Erygin, D., Berdov, B., Kang, Y., Tak, W., Park, J., Yeong Lim, H., Heo, J., Hyun Kim, J., Kim, T., Jin Choi, H., Varela, M., Elisa Reig Monzon, M., Sangro, B., Gómez Martin, C., Guillén Ponce, C., López, C., Cheng, A., Chao, Y., Feng, Y., Jeng, L., Hung, C., Hou, M., Wang Tsang-En Wang, J., Yen, C., Sukeepaisarnjaroen, W., Sunpaweravong, P., Charoentum, C., Tanasanvimon, S., Sirachainan, E., Ungtrakul, T., Prasongsook, N., Maneenil, K., Jitpewngarm, W., Ostapenko, Y., Skoryi, D., Bondarenko, I., Shparyk, Y., Trukhin, D., Hotko, Y., Ursol, G., Kryzhanivska, A., Abou-Alfa, G. K., Mody, K., Dayyani, F., Al-Rajabi, R., Yarchoan, M., Gandhi, S., Crysler, O., Ruth He, A., Reeves, J., Bahary, N., Mahipal, A., Kate Kelley, R., Dasgupta, A., Rowe, J., Thota, R., Beg, M., Morse, M., Choi, S., Crocenzi, T., Somer, B., Abrams, T., Denlinger, C., Zhang, Y., Sharma, N., Dao, T. V., Tien Thinh, N., Thi Tuyet Phuong, L., Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma, <<ANNALS OF ONCOLOGY>>, 2024; 35 (5): 448-457. [doi:10.1016/j.annonc.2024.02.005] [https://hdl.handle.net/10807/302085]
Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
Gasbarrini, Antonio;
2024
Abstract
Background: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. Patients and methods: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). Results: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. Conclusions: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.
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