|
|
阿替利珠联合贝伐珠治疗晚期肝癌的安全性及有效性的荟萃分析
|
Abstract:
目的：阿替利珠单抗(atezolizumab)联合贝伐珠单抗(bevacizumab)于2020年被中国国家药品监督管理局批准作为晚期肝细胞癌(HCC)的一线治疗药物。但各随机对照试验(RCT)及回顾性研究报道的两药安全性及有效性不尽相同，本研究的目的是进一步评估两者联合治疗晚期HCC的有效性及安全性。方法：在Web of Science、PubMed、Embase、Cochrane、CBM、知网、万方、维普各数据库检索了2018年1月1日至2023年10月1日关于阿替利珠单抗联合贝伐单抗来治疗晚期HCC的合格文献。结果包括总缓解率(OR)、完全缓解率(CR)、部分缓解率(PR)、中位总生存期(mOS)、中位无进展生存期(mPFS)和不良事件(AE)。结果：纳入了42项研究，包括3168名患者。基于实体瘤反应评价标准(RECIST)的长期(超过6周)治疗反应的OR、CR和PR分别为26%、3%和23%。合并的总生存期为12.2个月，合并中位无进展生存期为6.9个月。在治疗期间，63%的患者发生了不良事件，其中3级及以上的不良事件的发生率为42%。结论：阿替利珠单抗联合贝伐单抗治疗晚期HCC有效性和安全性良好。阿替利珠单抗联合贝伐单抗在晚期HCC的长期、一线和标准剂量治疗中显示出较好的肿瘤缓解率。
Objective: Atezolizumab in combination with bevacizumab was approved by the National Medical Products Administration of China in 2020 as the first-line treatment for advanced hepatocellular carcinoma (HCC). However, the safety and efficacy reported varied between randomized controlled trials (RCT) and retrospective studies. The purpose of this study was to further evaluate the efficacy and safety of the combination in the treatment of advanced HCC. Method: The databases of Web of Science, PubMed, Embase, Cochrane, CBM, CNKI, Wanfang, and Virpup for the combination of bevacizumab and bevacizumab for advanced HCC were searched from January 1, 2018 to October 1, 2023. The results included the overall response rate (OR), complete response rate (CR), partial response rate (PR), median overall survival (mOS), median progression-free survival (mPFS), and adverse events (AEs). Results: 42 studies were included, including 3168 patients. The OR, CR, and PR for long-term treatment response (over 6 weeks) based on the response evaluation criteria (RECIST) for solid tumors were 26%, 3%, and 23%, respectively. The combined overall survival was 12.2 months, and the combined median progression-free survival was 6.9 months. During the treatment period, 63% of the patients had adverse events, with the incidence of grade 3 and above being 42%. Conclusion: Atezolizumab combined with bevacizumab in advanced HCC. Altelibizumab combined with bevacizumab showed better tumor response rates in long-term, first-line and standard dose therapy for advanced HCC.
| [1] | Kim, E. and Viatour, P. (2020) Hepatocellular Carcinoma: Old Friends and New Tricks. Experimental & Molecular Medicine, 52, 1898-1907. https://doi.org/10.1038/s12276-020-00527-1 |
| [2] | Rinaldi, L., Guarino, M., Perrella, A., Pafundi, P.C., Valente, G., Fontanella, L., et al. (2019) Role of Liver Stiffness Measurement in Predicting HCC Occurrence in Direct-Acting Antivirals Setting: A Real-Life Experience. Digestive Diseases and Sciences, 64, 3013-3019. https://doi.org/10.1007/s10620-019-05604-8 |
| [3] | Rich, N.E., Yopp, A.C., Singal, A.G. and Murphy, C.C. (2020) Hepatocellular Carcinoma Incidence Is Decreasing among Younger Adults in the United States. Clinical Gastroenterology and Hepatology, 18, 242-248.e5. https://doi.org/10.1016/j.cgh.2019.04.043 |
| [4] | Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660 |
| [5] | 孙惠川, 谢青, 荚卫东, 等. 肝癌转化治疗中国专家共识(2021版) [J]. 中国实用外科杂志, 2021, 41(6): 618-632. |
| [6] | Llovet, J.M., Real, M.I., Montaña, X., Planas, R., Coll, S., Aponte, J., et al. (2002) Arterial Embolisation or Chemoembolisation versus Symptomatic Treatment in Patients with Unresectable Hepatocellular Carcinoma: A Randomised Controlled Trial. The Lancet, 359, 1734-1739. https://doi.org/10.1016/s0140-6736(02)08649-x |
| [7] | Bouattour, M., Mehta, N., He, A.R., Cohen, E.I. and Nault, J. (2019) Systemic Treatment for Advanced Hepatocellular Carcinoma. Liver Cancer, 8, 341-358. https://doi.org/10.1159/000496439 |
| [8] | US Food and Drug Administration (2020) FDA Approves Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-atezolizumab-plus-bevacizumab-unresectable-hepatocellular-carcinoma |
| [9] | Finn, R.S., Qin, S., Ikeda, M., Galle, P.R., Ducreux, M., Kim, T., et al. (2020) Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. New England Journal of Medicine, 382, 1894-1905. https://doi.org/10.1056/nejmoa1915745 |
| [10] | Macaluso, F.S., Maida, M., Ventimiglia, M. and Orlando, A. (2022) Effectiveness and Safety of Tofacitinib for the Treatment of Ulcerative Colitis: A Single-Arm Meta-Analysis of Observational Studies. Digestive and Liver Disease, 54, 183-191. https://doi.org/10.1016/j.dld.2021.04.018 |
| [11] | Lee, M.S., Ryoo, B., Hsu, C., Numata, K., Stein, S., Verret, W., et al. (2020) Atezolizumab with or without Bevacizumab in Unresectable Hepatocellular Carcinoma (GO30140): An Open-Label, Multicentre, Phase 1b Study. The Lancet Oncology, 21, 808-820. https://doi.org/10.1016/s1470-2045(20)30156-x |
| [12] | Gao, X., Zhao, R., Ma, H. and Zuo, S. (2023) Efficacy and Safety of Atezolizumab plus Bevacizumab Treatment for Advanced Hepatocellular Carcinoma in the Real World: A Single-Arm Meta-Analysis. BMC Cancer, 23, Article No. 635. https://doi.org/10.1186/s12885-023-11112-w |
| [13] | Moola, S., Munn, Z., Sears, K., Sfetcu, R., Currie, M., Lisy, K., et al. (2015) Conducting Systematic Reviews of Association (Etiology): The Joanna Briggs Institute’s Approach. International Journal of Evidence-Based Healthcare, 13, 163-169. https://doi.org/10.1097/xeb.0000000000000064 |
| [14] | Lo, C.K., Mertz, D. and Loeb, M. (2014) Newcastle-Ottawa Scale: Comparing Reviewers’ to Authors’ Assessments. BMC Medical Research Methodology, 14, Article No. 45. https://doi.org/10.1186/1471-2288-14-45 |
| [15] | De Castro, T., Jochheim, L.S., Bathon, M., Welland, S., Scheiner, B., Shmanko, K., et al. (2022) Atezolizumab and Bevacizumab in Patients with Advanced Hepatocellular Carcinoma with Impaired Liver Function and Prior Systemic Therapy: A Real-World Experience. Therapeutic Advances in Medical Oncology, 14, Article 17588359221080298. |
| [16] | Teng, W., Lin, C., Lin, P., Hsieh, Y., Ho, M., Hsieh, C., et al. (2022) Combination of CRAFITY Score with Alpha-Fetoprotein Response Predicts a Favorable Outcome of Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma. Journal of Hepatology, 77, S373. https://doi.org/10.1016/s0168-8278(22)01098-4 |
| [17] | Komatsu, S., Yano, Y., Fujishima, Y., Ishida, J., Kido, M., Kuramitsu, K., et al. (2022) Current Role of Atezolizumab plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. Anticancer Research, 42, 1403-1412. https://doi.org/10.21873/anticanres.15610 |
| [18] | Cheon, J., Yoo, C., Hong, J.Y., Kim, H.S., Lee, D., Lee, M.A., et al. (2022) Efficacy and Safety of Atezolizumab plus Bevacizumab in Korean Patients with Advanced Hepatocellular Carcinoma. Liver International, 42, 674-681. https://doi.org/10.1111/liv.15102 |
| [19] | Himmelsbach, V., Pinter, M., Scheiner, B., Venerito, M., Sinner, F., Zimpel, C., et al. (2022) Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers. Cancers, 14, Article 1722. https://doi.org/10.3390/cancers14071722 |
| [20] | Maesaka, K., Sakamori, R., Yamada, R., Tahata, Y., Imai, Y., Ohkawa, K., et al. (2022) Hyperprogressive Disease in Patients with Unresectable Hepatocellular Carcinoma Receiving Atezolizumab plus Bevacizumab Therapy. Hepatology Research, 52, 298-307. https://doi.org/10.1111/hepr.13741 |
| [21] | Iwamoto, H., Shimose, S., Noda, Y., Shirono, T., Niizeki, T., Nakano, M., et al. (2021) Initial Experience of Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. Cancers, 13, Article 2786. https://doi.org/10.3390/cancers13112786 |
| [22] | Sho, T., Suda, G., Yamamoto, Y., Furuya, K., Baba, M., Ogawa, K., et al. (2022) Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150. Cancers, 14, 3938. https://doi.org/10.3390/cancers14163938 |
| [23] | Chon, Y.E., Cheon, J., Kim, H., Kang, B., Ha, Y., Kim, D.Y., et al. (2023) Predictive Biomarkers of Survival in Patients with Advanced Hepatocellular Carcinoma Receiving Atezolizumab plus Bevacizumab Treatment. Cancer Medicine, 12, 2731-2738. https://doi.org/10.1002/cam4.5161 |
| [24] | Gulati, P., Taneja, S., Duseja, A. and Singh, V. (2022) Letter to the Editor: Preliminary Evidence of Safety and Tolerability of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma and Child‐Pugh a and B Cirrhosis: A Real‐World Study—Should We Extend the Boundaries? Hepatology, 76, E80-E81. https://doi.org/10.1002/hep.32554 |
| [25] | Eso, Y., Takeda, H., Taura, K., Takai, A., Takahashi, K. and Seno, H. (2021) Pretreatment Neutrophil-to-Lymphocyte Ratio as a Predictive Marker of Response to Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma. Current Oncology, 28, 4157-4166. https://doi.org/10.3390/curroncol28050352 |
| [26] | Chen, C., Feng, Y., Yen, C., Chen, S., Lin, Y., Lu, L., et al. (2022) Prognosis and Treatment Pattern of Advanced Hepatocellular Carcinoma after Failure of First-Line Atezolizumab and Bevacizumab Treatment. Hepatology International, 16, 1199-1207. https://doi.org/10.1007/s12072-022-10392-x |
| [27] | Fulgenzi, C.A.M., Cheon, J., D’Alessio, A., Nishida, N., Ang, C., Marron, T.U., et al. (2022) Reproducible Safety and Efficacy of Atezolizumab plus Bevacizumab for HCC in Clinical Practice: Results of the AB-Real Study. European Journal of Cancer, 175, 204-213. https://doi.org/10.1016/j.ejca.2022.08.024 |
| [28] | Tada, T., Kumada, T., Hiraoka, A., Hirooka, M., Kariyama, K., Tani, J., et al. (2022) Safety and Efficacy of Atezolizumab plus Bevacizumab in Elderly Patients with Hepatocellular Carcinoma: A Multicenter Analysis. Cancer Medicine, 11, 3796-3808. https://doi.org/10.1002/cam4.4763 |
| [29] | Chuma, M., Uojima, H., Hattori, N., Arase, Y., Fukushima, T., Hirose, S., et al. (2022) Safety and Efficacy of Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma in Early Clinical Practice: A Multicenter Analysis. Hepatology Research, 52, 269-280. https://doi.org/10.1111/hepr.13732 |
| [30] | Wang, J., Chen, Y., Kee, K., Wang, C., Tsai, M., Kuo, Y., et al. (2022) The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma Receiving Atezolizumab plus Bevacizumab. Cancers, 14, Article 343. https://doi.org/10.3390/cancers14020343 |
| [31] | Kim, B.K., Cheon, J., Kim, H., Kang, B., Ha, Y., Kim, D.Y., et al. (2022) Atezolizumab/bevacizumab Vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study. Cancers, 14, Article 1747. https://doi.org/10.3390/cancers14071747 |
| [32] | Hiraoka, A., Kumada, T., Tada, T., Hirooka, M., Kariyama, K., Tani, J., et al. (2023) Does First‐Line Treatment Have Prognostic Impact for Unresectable HCC?—Atezolizumab plus Bevacizumab versus Lenvatinib. Cancer Medicine, 12, 325-334. https://doi.org/10.1002/cam4.4854 |
| [33] | Cheng, A., Qin, S., Ikeda, M., Galle, P.R., Ducreux, M., Kim, T., et al. (2022) Updated Efficacy and Safety Data from Imbrave150: Atezolizumab plus Bevacizumab vs. Sorafenib for Unresectable Hepatocellular Carcinoma. Journal of Hepatology, 76, 862-873. https://doi.org/10.1016/j.jhep.2021.11.030 |
| [34] | Maesaka, K., Sakamori, R., Yamada, R., Doi, A., Tahata, Y., Miyazaki, M., et al. (2022) Comparison of Atezolizumab plus Bevacizumab and Lenvatinib in Terms of Efficacy and Safety as Primary Systemic Chemotherapy for Hepatocellular Carcinoma. Hepatology Research, 52, 630-640. https://doi.org/10.1111/hepr.13771 |
| [35] | Su, C., Teng, W., Lin, P., Jeng, W., Chen, K., Hsieh, Y., et al. (2023) Similar Efficacy and Safety between Lenvatinib versus Atezolizumab plus Bevacizumab as the First‐Line Treatment for Unresectable Hepatocellular Carcinoma. Cancer Medicine, 12, 7077-7089. https://doi.org/10.1002/cam4.5506 |
| [36] | Jost‐Brinkmann, F., Demir, M., Wree, A., Luedde, T., Loosen, S.H., Müller, T., et al. (2023) Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma: Results from a German Real‐World Cohort. Alimentary Pharmacology & Therapeutics, 57, 1313-1325. https://doi.org/10.1111/apt.17441 |
| [37] | Tada, T., Kumada, T., Hiraoka, A., Hirooka, M., Kariyama, K., Tani, J., et al. (2023) Comparison of Prognostic Impact of Atezolizumab plus Bevacizumab versus Lenvatinib in Patients with Intermediate‐Stage Hepatocellular Carcinoma. Liver International, 44, 113-124. https://doi.org/10.1111/liv.15753 |
| [38] | Vithayathil, M., D’Alessio, A., Fulgenzi, C.A.M., Nishida, N., Schönlein, M., von Felden, J., et al. (2023) Impact of Body Mass Index in Patients Receiving Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma. Hepatology International, 17, 904-914. https://doi.org/10.1007/s12072-023-10491-3 |
| [39] | Lee, Y., Huang, W., Lee, M., Tsao, C. and Feng, Y. (2023) In Vivo, 37, 454-460. https://doi.org/10.21873/invivo.13099 |
| [40] | Fukushima, T., Morimoto, M., Kobayashi, S., Ueno, M., Uojima, H., Hidaka, H., et al. (2023) Association between Immune-Related Adverse Events and Survival in Patients with Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab. The Oncologist, 28, e526-e533. https://doi.org/10.1093/oncolo/oyad090 |
| [41] | Hatanaka, T., Kakizaki, S., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., et al. (2023) Association of Proton Pump Inhibitor and Antibiotic Use with the Clinical Outcomes of Hepatocellular Carcinoma Patients Receiving Atezolizumab and Bevacizumab: A Multicenter Analysis. Hepatology Research, 53, 737-748. https://doi.org/10.1111/hepr.13905 |
| [42] | Jeschke, M., Ludwig, J.M., Leyh, C., Pabst, K.M., Weber, M., Theysohn, J.M., et al. (2023) Bilobar Radioembolization Carries the Risk of Radioembolization-Induced Liver Disease in the Treatment of Advanced Hepatocellular Carcinoma: Safety and Efficacy Comparison to Systemic Therapy with Atezolizumab/Bevacizumab. Cancers, 15, Article 4274. https://doi.org/10.3390/cancers15174274 |
| [43] | Tanabe, N., Saeki, I., Aibe, Y., Matsuda, T., Hanazono, T., Nishi, M., et al. (2023) Early Prediction of Response Focused on Tumor Markers in Atezolizumab plus Bevacizumab Therapy for Hepatocellular Carcinoma. Cancers, 15, Article 2927. https://doi.org/10.3390/cancers15112927 |
| [44] | Maesaka, K., Sakamori, R., Yamada, R., Doi, A., Tahata, Y., Ohkawa, K., et al. (2023) Pretreatment with Antibiotics Is Associated with Reduced Therapeutic Response to Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma. PLOS ONE, 18, e0281459. https://doi.org/10.1371/journal.pone.0281459 |
| [45] | Hiraoka, A., Kumada, T., Tada, T., Hirooka, M., Kariyama, K., Tani, J., et al. (2023) Geriatric Nutritional Risk Index as an Easy‐to‐Use Assessment Tool for Nutritional Status in Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab. Hepatology Research, 53, 1031-1042. https://doi.org/10.1111/hepr.13934 |
| [46] | Tada, T., Kumada, T., Hiraoka, A., Hirooka, M., Kariyama, K., Tani, J., et al. (2023) Impact of First‐Line Systemic Therapy with Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma. Journal of Gastroenterology and Hepatology, 38, 1389-1397. https://doi.org/10.1111/jgh.16225 |
| [47] | Takeuchi, Y., Nouso, K., Fujioka, S., Kariyama, K., Kobashi, H., Uematsu, S., et al. (2023) The Prediction of Early Progressive Disease in Patients with Hepatocellular Carcinoma Receiving Atezolizumab plus Bevacizumab. Cancer Medicine, 12, 17559-17568. https://doi.org/10.1002/cam4.6369 |
| [48] | Matoya, S., Suzuki, T., Matsuura, K., Suzuki, Y., Okumura, F., Nagura, Y., et al. (2023) The Neutrophil‐to‐lymphocyte Ratio at the Start of the Second Course during Atezolizumab plus Bevacizumab Therapy Predicts Therapeutic Efficacy in Patients with Advanced Hepatocellular Carcinoma: A Multicenter Analysis. Hepatology Research, 53, 511-521. https://doi.org/10.1111/hepr.13886 |
| [49] | Tanaka, K., Tsuji, K., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., et al. (2023) Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab: A Multicenter Retrospective Study. Cancers, 15, Article 4348. https://doi.org/10.3390/cancers15174348 |
| [50] | Shimose, S., Iwamoto, H., Shirono, T., Tanaka, M., Niizeki, T., Kajiwara, M., et al. (2023) The Impact of Curative Conversion Therapy Aimed at a Cancer‐free State in Patients with Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab. Cancer Medicine, 12, 12325-12335. https://doi.org/10.1002/cam4.5931 |
| [51] | Kudo, M., Aoki, T., Ueshima, K., Tsuchiya, K., Morita, M., Chishina, H., et al. (2023) Achievement of Complete Response and Drug-Free Status by Atezolizumab plus Bevacizumab Combined with or without Curative Conversion in Patients with Transarterial Chemoembolization-Unsuitable, Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Proof-of-Concept Study. Liver Cancer, 12, 321-338. https://doi.org/10.1159/000529574 |
| [52] | Takada, H., Yamashita, K., Osawa, L., Komiyama, Y., Muraoka, M., Suzuki, Y., et al. (2024) Significance of the Autoantibody Assay in Predicting the Development of Immune‐Related Adverse Events in Patients Receiving Atezolizumab plus Bevacizumab Combination Therapy for Unresectable Hepatocellular Carcinoma. Hepatology Research, 54, 162-173. https://doi.org/10.1111/hepr.13969 |
| [53] | Casadei-Gardini, A., Rimini, M., Tada, T., et al. (2023) Atezolizumab plus Bevacizumab versus Lenvatinib for Unresectable Hepato-Cellular Carcinoma: A Large Real-Life Worldwide Population. European Journal of Cancer, 180, 9-20. |
| [54] | Ohama, H., Hiraoka, A., Tada, T., Hirooka, M., Kariyama, K., Tani, J., et al. (2023) Comparison between Atezolizumab plus Bevacizumab and Lenvatinib for Hepatocellular Carcinoma in Patients with Child-Pugh Class B in Real-World Clinical Settings. Oncology, 101, 542-552. https://doi.org/10.1159/000530028 |
| [55] | Rimini, M., Persano, M., Tada, T., Suda, G., Shimose, S., Kudo, M., et al. (2023) Survival Outcomes from Atezolizumab plus Bevacizumab versus Lenvatinib in Child Pugh B Unresectable Hepatocellular Carcinoma Patients. Journal of Cancer Research and Clinical Oncology, 149, 7565-7577. https://doi.org/10.1007/s00432-023-04678-2 |
| [56] | Herbst, R.S., Soria, J., Kowanetz, M., Fine, G.D., Hamid, O., Gordon, M.S., et al. (2014) Predictive Correlates of Response to the Anti-PD-L1 Antibody MPDL3280A in Cancer Patients. Nature, 515, 563-567. https://doi.org/10.1038/nature14011 |
| [57] | Liu, X., Lu, Y. and Qin, S. (2021) Atezolizumab and Bevacizumab for Hepatocellular Carcinoma: Mechanism, Pharmacokinetics and Future Treatment Strategies. Future Oncology, 17, 2243-2256. https://doi.org/10.2217/fon-2020-1290 |
| [58] | Boige, V., Malka, D., Bourredjem, A., Dromain, C., Baey, C., Jacques, N., et al. (2012) Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma. The Oncologist, 17, 1063-1072. https://doi.org/10.1634/theoncologist.2011-0465 |
| [59] | Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674. https://doi.org/10.1016/j.cell.2011.02.013 |
| [60] | Zhu, A.X., Abbas, A.R., de Galarreta, M.R., Guan, Y., Lu, S., Koeppen, H., et al. (2022) Molecular Correlates of Clinical Response and Resistance to Atezolizumab in Combination with Bevacizumab in Advanced Hepatocellular Carcinoma. Nature Medicine, 28, 1599-1611. https://doi.org/10.1038/s41591-022-01868-2 |
