Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Persano, M.; Rimini, M.; Tada, T.; Suda, G.; Shimose, S.; Kudo, M.; Cheon, J.; Finkelmeier, F.; Lim, H. Y.; Presa, J.; Masi, G.; Yoo, C.; Lonardi, S.; Tovoli, F.; Kumada, T.; Sakamoto, N.; Iwamoto, H.; Aoki, T.; Chon, H. J.; Himmelsbach, V.; Niizeki, T.; Montes, M.; Vivaldi, C.; Solda, C.; Stefanini, B.; Hiraoka, A.; Sho, T.; Nishida, N.; Steup, C.; Iavarone, M.; Di Costanzo, G.; Marra, F.; Tamburini, E.; Cabibbo, G.; Foschi, F. G.; Silletta, M.; Hirooka, M.; Kariyama, K.; Tani, J.; Atsukawa, M.; Takaguchi, K.; Itobayashi, E.; Fukunishi, S.; Tsuji, K.; Ishikawa, T.; Tajiri, K.; Ochi, H.; Yasuda, S.; Toyoda, H.; Ogawa, C.; Nishimura, T.; Hatanaka, T.; Kakizaki, S.; Shimada, N.; Kawata, K.; Tada, F.; Ohama, H.; Nouso, K.; Morishita, A.; Tsutsui, A.; Nagano, T.; Itokawa, N.; Okubo, T.; Arai, T.; Imai, M.; Kosaka, H.; Naganuma, A.; Koizumi, Y.; Nakamura, S.; Kaibori, M.; Iijima, H.; Hiasa, Y.; Campani, C.; Amadeo, E.; Rossari, F.; Burgio, V.; Cascinu, S.; Scartozzi, M.; Casadei-Gardini, A.

doi:10.1016/j.ejca.2023.05.021

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab. Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line. Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6 months) and atezolizumab plus bevacizumab first-line (15.7 months; p = 0.12; hazard ratio [HR] = 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who underwent trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8 months, p < 0.01; HR = 0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0 months) and those who underwent TACE (15.9 months) had a significative longer OS than patients treated with sorafenib (14.2 months; respectively, p = 0.01; HR = 0.45, and p < 0.05; HR = 0.46). Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy.

Persano M., Rimini M., Tada T., Suda G., Shimose S., Kudo M., et al. (2023). Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients. EUROPEAN JOURNAL OF CANCER, 189, 1-13 [10.1016/j.ejca.2023.05.021].