Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
Authors: B. Sangro, S.L. Chan, R.K. Kelley, G. Lau, M. Kudo, W. Sukeepaisarnjaroen, M. Yarchoan, E.N. De Toni, J. Furuse, Y.K. Kang, P.R. Galle, L. Rimassa, A. Heurgué, V.C. Tam, T. Van Dao, S.C. Thungappa, V. Breder, Y. Ostapenko, M. Reig, M. Makowsky, M.J. Paskow, C. Gupta, J.F. Kurland, A. Negro, G.K. Abou-Alfa, Sergio Azevedo, Maria Ignez Braghiroli, Gustavo Girotto, Arinilda Bragagnoli, Ricardo Branco, Adilson Faccio, Andrea Moretto, Nils Skare, Jamille Dutra, Luciana Viola, Karina Vianna, Fernando Meton, Claudia Sette, Amanda Faulhaber, Vincent C. Tam, Felix Couture, Jim Biagi, Helene Castel, Karen Mulder, Yoo-Joung Ko, Kevin Zbuk, Stephen Welch, Annie Beaudoin, Alexandra Heurgué, Eric Assenat, Isabelle Archambeaud, David Tougeron, Jean-Marie Peron, Marine Gilabert, Jean-Pierre Bronowicki, Stephane Cattan, Jean-Frederic Blanc, Mohamed Bouattour, Jean-Marc Phelip, Valerie Boige, Pierre Michel, Anne-Claire Frin, Enrico N. De Toni, Marie-Luise Berres, Arndt Vogel, Thomas Berg, Thomas Ettrich, Dirk Waldschmidt, Hans Heinrich Wedemeyer, Marcus-Alexander Worns, Michael Bitzer, Karl-Heinz Weiss, George Lau, Stephen L. Chan, Thomas Yau, Yin Ping Tai, Ann Shing Lee, Satheesh Chiradoni Thungappa, Lokesh K. N, Vikas Sureshchand Ostwal, Kattimani Kiran Ashok, Sushant Mittal, Hari Goyal, Sankar Srinivasan, Ghanashyam Biswas, Mallavarapu Mohan, Sewanti Limaye, Nirav Asarawala, Lorenza Rimassa, Alfredo Falcone, Luca Gianni, Antonio Gasbarrini, Bruno Daniele, Antonio Avallone, Giovanni Luca Paolo Frassineti, Fausto Roila, Masatoshi Kudo, Tomokazu Kawaoka, Manabu Morimoto, Yasuhiro Takikawa, Naoya Kato, Tatsuya Yamashita, Yukio Osaki, Kenta Motomura, Ryosuke Tateishi, Kazuyoshi Ohkawa, Yoshiyuki Wada, Hideki Onishi, Naoki Sasahira, Yoshitaka Inaba, Masayuki Kurosaki, Kunihiko Tsuji, Yoshiyuki Takei, Takeshi Aramaki, Atsushi Hagihara, Junji Furuse, Kiyohide Kioka, Hironori Koga, Yutaka Sasaki, Kazushi Numata, Toshifumi Tada, Yasunori Kawaguchi, Seijin Nadano, Alexander Vasilyev, Valery Breder, Oleg Lipatov, Mikhail Dvorkin, Oleg Zarubenkov, Svetlana Kutukova, Roman Ponomarev, Kirill Shostka, Anna Alyasova, Eldar Topuzov, Alexey Severtsev, Yuryi Petrov, Dmitriy Erygin, Boris Berdov, Yoon-Koo Kang, Won-Young Tak, Joong-Won Park, Ho Yeong Lim, Jeong Heo, Jee Hyun Kim, Tae-You Kim, Hye Jin Choi, María Varela, María Elisa Reig Monzon, Bruno Sangro, Carlos Gómez Martin, Carmen Guillén Ponce, Carlos López, Ann-Lii Cheng, Yee Chao, Yin-Hsun Feng, Long-Bin Jeng, Chao-Hung Hung, Ming-Mo Hou, Jing-Houng Wang Tsang-En Wang, Chia-Jui Yen, Wattana Sukeepaisarnjaroen, Patrapim Sunpaweravong, Chaiyut Charoentum, Suebpong Tanasanvimon, Ekaphop Sirachainan, Teerapat Ungtrakul, Naiyarat Prasongsook, Kunlatida Maneenil, Wittawat Jitpewngarm, Yurii Ostapenko, Denys Skoryi, Igor Bondarenko, Yaroslav Shparyk, Dmytro Trukhin, Yevhen Hotko, Grygorii Ursol, Anna Kryzhanivska, Ghassan K. Abou-Alfa, Kabir Mody, Farshid Dayyani, Raed Al-Rajabi, Mark Yarchoan, Sunil Gandhi, Oxana Crysler, Aiwu Ruth He, James Reeves, Nathan Bahary, Amit Mahipal, Robin Kate Kelley, Anirudha Dasgupta, Julie Rowe, Ramya Thota, Muhammad Beg, Michael Morse, Sung-hee Choi, Todd Crocenzi, Bradley Somer, Thomas Abrams, Crystal Denlinger, Yue Zhang, Nisha Sharma, Tu V. Dao, Nguyen Tien Thinh, Le Thi Tuyet Phuong
Journal: Annals of Oncology (2024)

BackgroundIn 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 four-year updated OS analysis of HIMALAYA.Patients and methodsParticipants 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 January 23, 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).ResultsFor STRIDE, durvalumab, and sorafenib, median (95% CI) follow-up was 49.12 (46.95-50.17), 48.46 (46.82-49.81), and 47.31 (45.08-49.15) months, respectively. OS HR (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.ConclusionsThese data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented three- and four-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.