Paclitaxel

肝细胞癌（HCC）占原发性肝癌的90%，是全球主要癌症致死病因之一，病因包括乙肝/丙肝感染、代谢相关脂肪性肝病、酒精性肝病等。其5年生存率不足20%，多数患者确诊时已为晚期，失去根治性切除的机会。近年来，免疫检查点抑制剂（ICIs）、酪氨酸激酶抑制剂（TKIs）及其联合方案虽重塑治疗格局，但大多数患者仍无法获得持续的临床获益，复发率高。HCC特有的免疫抑制肿瘤微环境是疗效受限的关键，抗血管生成药物、化疗与免疫治疗具有协同作用，联合方案可改善生存，但细胞层面机制仍不清晰。《Journal of Hematology & Oncology》发表的一项综述总结了HCC免疫联合治疗的机制，阐述临床疗效和局限、生物标志物及技术进展，为个体化治疗方案设计提供理论依据。 HCC的免疫治疗：细胞视角 HCC的免疫景观 肝细胞癌处于慢性炎症与免疫抑制微环境中，属于低免疫原性肿瘤。CD8+ T细胞耗竭、程序性死亡受体1/细胞毒性T淋巴细胞相关抗原4（PD-1/CTLA-4）等检查点上调是免疫核心障碍；调节性T细胞（Tregs）、髓源性抑制细胞（MDSCs）、M2型肿瘤相关巨噬细胞（TAMs）等抑制细胞大量富集，纤维化基质也形成物理屏障，共同阻碍免疫治疗。PD-L1高表达、肿瘤免疫表型异质性进一步导致耐药与疗效差异，亟需联合治疗来突破免疫抑制。 图1 HCC的免疫抑制微环境 （来源于《Journal of Hematology & Oncology》期刊官网：Dai S, et al. J Hematol Oncol. 2025 Sep 26;18(1):85.） ICIs在HCC中的作用机制 ICIs通过阻断PD-1/PD-L1、CTLA-4通路，恢复T细胞抗肿瘤活性，逆转肝癌免疫逃逸。阻断PD-1通路可重新激活耗竭T细胞，阻断CTLA-4通路能增强T细胞启动、减轻免疫抑制。这类药物还可重塑免疫微环境，但单药缓解率仅15%~20%，易因代偿性检查点上调产生耐药。因此临床正积极探索免疫联合靶向、化疗或双免疫方案，以突破免疫屏障、提升疗效。 图2 ICIs在HCC中的作用机制 （来源于《Journal of Hematology & Oncology》期刊官网：Dai S, et al. J Hematol Oncol. 2025 Sep 26;18(1):85.） 联合治疗策略及其细胞机制 ICIs+TKIs HCC中影响ICI疗效的免疫和血管屏障 HCC血管异常、缺氧及血管内皮生长因子（VEGF）高表达，会形成免疫抑制微环境并降低免疫治疗效果。TKIs可抑制VEGF通路，使肿瘤血管正常化、缓解缺氧、促进T细胞浸润，还能下调免疫抑制因子、改善抗原呈递。部分TKIs还可靶向间质上皮细胞转化因子（MET）、酪氨酸蛋白激酶受体AXL等通路实现广谱免疫重编程，与ICIs机制互补、产生协同效应，为HCC个体化联合治疗提供了关键依据。 ICIs与TKIs的协同机制 TKIs与ICIs在HCC中存在协同作用。TKI通过阻断缺氧-VEGF轴，使肿瘤血管正常化、缓解缺氧，促进CD8+ T细胞浸润，并将M2型巨噬细胞重编程为M1型，同时减少MDSCs与Tregs。TKI还能促进树突状细胞成熟、增强抗原呈递。临床前研究证实该联合方案可显著提升抗肿瘤效果，但疗效受肿瘤免疫表型影响，需以生物标志物指导个体化治疗。 图3 ICIs与TKIs的协同机制 （来源于《Journal of Hematology & Oncology》期刊官网：Dai S, et al. J Hematol Oncol. 2025 Sep 26;18(1):85.） ICIs联合化疗 机制原理：化疗如何启动免疫应答 部分化疗药可诱导HCC细胞发生免疫原性细胞死亡，释放抗原激活树突状细胞，增强CD8+ T细胞应答。奥沙利铂、5‑氟尿嘧啶（5-FU）、吉西他滨等能清除髓源性抑制细胞、调节性T细胞，改善免疫微环境。但5-FU存在双向作用，紫杉醇、高剂量环磷酰胺反而抑制免疫。因此化疗需精准选药与控量，才能与免疫治疗协同增效。 免疫协同作用与肿瘤微环境重塑 化疗可重塑HCC肿瘤微环境，通过诱导肿瘤细胞死亡、释放抗原、清除免疫抑制细胞，将微环境转为促炎状态。化疗还能调节细胞因子、促进树突状细胞成熟、改善基质屏障以增强免疫浸润，部分药物可上调PD-L1提升免疫治疗敏感性。此外，化疗可调控肠道菌群，且给药顺序影响协同效果，相关联合方案已进入临床试验。 图4 免疫协同作用与肿瘤微环境重塑 （来源于《Journal of Hematology & Oncology》期刊官网：Dai S, et al. J Hematol Oncol. 2025 Sep 26;18(1):85.） 双ICIs（PD-1/PD-L1联合CTLA-4）策略 机制原理：PD-1和CTLA-4阻断的互补作用 联合使用PD-1/PD-L1与CTLA-4抑制剂的双重ICIs疗法，其理论基础在于二者作用互补：前者恢复肿瘤微环境中耗竭T细胞功能，后者在淋巴组织早期促进T细胞启动与抗原呈递，协同提升抗肿瘤免疫。该方案可能对免疫炎症型HCC效果更优，临床研究证实其疗效优于免疫单药。但双重阻断通常与更高的免疫相关不良事件（irAEs）发生率相关，目前可通过优化给药方案在保证疗效的同时降低毒性。 双阻断的免疫协同作用与功能结局 双免疫检查点阻断可同时调控T细胞启动与效应阶段，增强细胞毒性、细胞因子释放与杀瘤能力，还能活化NK细胞、减少Treg、诱发表位扩散并形成免疫记忆，实现长效抗肿瘤。该方案可能对免疫炎症型HCC疗效更佳，但易引发免疫相关不良反应。目前通过优化给药、研发双特异性抗体降低毒性，未来需依托生物标志物实现精准分层治疗。 图5 双重免疫检查点阻断在HCC中的机制协同效应 （来源于《Journal of Hematology & Oncology》期刊官网：Dai S, et al. J Hematol Oncol. 2025 Sep 26;18(1):85.） HCC免疫联合治疗的免疫机制比较 HCC免疫联合治疗依托互补的免疫调控机制发挥协同作用。ICIs联合TKIs方案中，TKIs可抗血管生成、清除免疫抑制细胞、增强T细胞浸润；ICIs联合化疗方案依靠化疗诱导免疫原性死亡、释放抗原并活化免疫；双免疫方案则同时靶向PD-1/PD-L1与CTLA-4通路，从启动和效应阶段双重激活T细胞。这三类联合策略均能重塑免疫抑制微环境，提升抗肿瘤效果。 临床前模型在研究联合治疗中的局限性 转化障碍：为何临床前模型无法预测HCC的临床结局 HCC免疫联合治疗的机制研究受限于现有临床前模型。多数模型仅评估单药，无法还原人体中HCC微环境的免疫、纤维化与血管复杂性，且缺少慢性肝病炎症背景。小鼠与人的肝脏代谢差异、无法模拟长期耐药等问题，也导致临床前疗效难以转化。常用异种移植模型缺乏功能性免疫，不适用于免疫治疗评价，亟需更贴合人体病理的模型。 模型特异性限制：评估免疫治疗研究中临床前系统的保真度 目前，HCC临床前模型均无法完整模拟免疫与基质的复杂特性。免疫缺陷模型无功能性免疫，基因工程与同基因模型缺少慢性炎症和纤维化，人源化模型技术难、成本高、免疫重建不全。3D类器官缺乏体内微环境，且所有模型实验周期短，无法模拟长期耐药。未来需构建整合免疫、基质、血管与纤维化的多维模型，以提升转化价值。 联合治疗中的新兴和创新概念 肿瘤异质性和免疫表型：联合治疗应答的决定因素 HCC病因与免疫表型呈高度异质性，是免疫治疗应答差异的核心原因。病毒相关HCC对免疫治疗应答更高，代谢相关HCC疗效较差。CTNNB1突变会抑制免疫浸润、导致耐药。HCC分免疫炎症型、排斥型、沙漠型三种表型，仅炎症型对免疫治疗敏感。单细胞测序、空间转录组等技术可用于分型与生物标志物筛选，指导精准联合治疗。 图6 HCC肿瘤的免疫表型及其对ICIs治疗反应的影响 （来源于《Journal of Hematology & Oncology》期刊官网：Dai S, et al. J Hematol Oncol. 2025 Sep 26;18(1):85.） 免疫逃逸和ICIs联合TKIs治疗耐药的表观遗传调控 表观遗传失调是HCC免疫逃逸的关键机制，DNA甲基化、组蛋白修饰及非编码RNA异常会抑制抗原呈递、上调PD-L1并加剧T细胞耗竭，还会引发靶向药物耐药。DNA甲基转移酶抑制剂（DNMTis）和组蛋白去乙酰化酶抑制剂（HDACis）等表观遗传调节剂可重塑免疫微环境、增强免疫治疗应答，目前相关联合临床试验正在开展。但这类药物脱靶效应明显，需结合生物标志物与免疫表型实现精准应用。 微生物群-免疫相互作用：增强免疫治疗的可调控轴 肠道菌群通过肠-肝轴调控HCC免疫，有益菌和短链脂肪酸可修复肠道屏障、改善免疫微环境，增强PD-1抑制剂疗效；菌群失调、抗生素使用则会降低免疫治疗效果。粪便移植、益生菌等可调节菌群，胆汁酸与特定菌属可作为疗效标志物。相关临床转化正在推进，有望成为提升HCC免疫治疗效果的新手段。 超越PD-1和CTLA-4：HCC中的新兴免疫检查点靶点 T细胞持续耗竭与免疫逃逸是PD-1/CTLA-4抑制剂单药治疗HCC疗效有限的主要原因。耗竭T细胞常共表达LAG-3、TIM-3、TIGIT、VISTA等替代检查点，引发耐药。这些靶点正成为联合治疗的关键方向，多项临床试验正在验证其与PD-1抑制剂联用的效果。未来需依托生物标志物分型，采用双特异性抗体等策略，实现精准多靶点免疫治疗。 基质和纤维化屏障：调节肿瘤微环境以提高ICIs疗效 HCC纤维化肿瘤微环境是免疫浸润的主要障碍，活化肝星状细胞与致密基质阻碍免疫细胞侵入。TGF‑β、CXCR4‑CXCL12轴、LOXL2是关键促纤维化与免疫抑制介质。抑制这些靶点可解除免疫排斥、增强免疫治疗效果。但基质参与组织修复，非选择性抑制易致肝损伤，未来需在生物标志物指导下精准靶向基质，提升免疫疗效。 未来展望与未解决的问题 未来展望 HCC免疫联合治疗仍面临疗效不均、耐药普遍等关键问题，未来发展需聚焦三大方向：一是建立多维生物标志物体系，将肿瘤特征、免疫微环境、肠道菌群与动态液体活检指标结合，替代单一标志物指导精准用药；二是系统攻克耐药机制，针对免疫检查点代偿上调、基质纤维化、代谢与表观遗传重编程等通路开发联合方案；三是利用人工智能与系统生物学整合多组学、影像数据，实现免疫表型与疗效预测。目前仍缺乏标准化工具与更贴近人体的临床前模型，是制约转化的核心瓶颈。 未解决的问题与讨论 当前HCC免疫联合治疗临床转化效果不佳，核心在于存在多重待解决难题。现有临床前模型难以复刻人体HCC纤维化、慢性炎症与复杂免疫微环境，导致实验结果难以落地。临床试验设计欠完善，剂量搭配、给药顺序及对照组设置不合理，造成多项优质联合方案试验失败。同时，HCC病因、人群特征高度异质，直接影响疗效差异。单一PD-L1、肿瘤突变负荷等标志物稳定性与预测价值有限，检测偏差明显。未来需优化临床前研究模型，规范试验设计，构建多维度整合型生物标志物体系，实现动态评估与个体化精准联合治疗。      结论      免疫联合治疗已成为晚期HCC的重要治疗方向，但其疗效并非依靠药物简单联用。本综述强调，需基于HCC免疫、纤维化及代谢特征，开展机制导向的方案设计，摒弃传统统一化治疗模式。依托动态生物标志物，匹配肿瘤免疫表型制定个体化联合策略。结合空间分析、系统生物学与人工智能，可优化治疗选择与耐药管控。未来研究需打通基础机制与临床应用的壁垒，推动HCC精准免疫治疗落地转化。 参考文献 Dai S, et al. Combination immunotherapy in hepatocellular carcinoma: synergies among immune checkpoints, TKIs, and chemotherapy. J Hematol Oncol. 2025 Sep 26;18(1):85. 审批编号：CN-184270 有效期至：2027-05-29 本文由阿斯利康提供，仅供医疗卫生专业人士参考，不可用于推广目的。 审校：Selina 排版：Liberos 执行：Atai 本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。

Filing acceptance is based on the Phase III Alliance ATOMIC study showing Tecentriq plus chemotherapy reduced recurrence or death risk by 50% versus chemotherapy alone Nearly one in three patients with stage III colon cancer relapse within five years, highlighting a critical need for new adjuvant treatment options If approved, Tecentriq plus chemotherapy could provide a new standard of care for the treatment of stage III dMMR/MSI-H colon cancer after surgery SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- $RHHBY --Genentech, a member of the Roche Group (SIX: RO, ROP; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) filing for adjuvant Tecentriq ® (atezolizumab) and Tecentriq Hybreza ® (atezolizumab and hyaluronidase-tqjs) in combination with chemotherapy in stage III deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) colon cancer, a type of tumor characterized by high mutation rates. The FDA has granted Priority Review and is expected to make a decision on the approval by October 9, 2026. “This filing acceptance brings us closer to establishing adjuvant Tecentriq plus chemotherapy as a new standard of care for certain types of early colon cancer," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “The ATOMIC results demonstrate that Tecentriq plus chemotherapy can substantially reduce the risk of disease recurrence or death, helping more patients remain cancer-free following surgery.” "One in three patients with stage III colon cancer will relapse within five years, underscoring the need for new adjuvant treatment options,” said Michael Sapienza, CEO, Colorectal Cancer Alliance. “This milestone represents a critical step toward a reality where treatment is tailored to a patient’s specific tumor biology from the very beginning, giving them a better chance of preventing a recurrence." The application is based on the landmark ATOMIC study, recently published in The New England Journal of Medicine . ATOMIC demonstrated that adding Tecentriq to standard FOLFOX6 chemotherapy reduced the risk of disease recurrence or death by 50%, compared to chemotherapy alone for people with stage III dMMR colon cancer, determined by an immunohistochemistry test, such as the VENTANA ® MMR RxDx Panel. The 36-month disease-free survival was 86% for Tecentriq combined with FOLFOX6 compared with 76% in the FOLFOX6 alone group. The safety pro consistent with previous studies of Tecentriq and FOLFOX6. Colon cancer remains one of the world's most common and deadliest tumors. Over one million people are diagnosed globally each year, and despite surgery and chemotherapy, approximately 30% of stage III patients relapse within five years. Approximately 15% of colon cancer patients present with dMMR/MSI-H tumors, which indicate a higher mutation rate and thus have the potential to respond to immunotherapy. The ATOMIC study was sponsored by the National Cancer Institute (NCI) and conducted by the Alliance for Clinical Trials in Oncology in partnership with Genentech and the Arbeitsgemeinschaft Internistische Onkologie (AIO) group in Germany. It highlights Genentech’s commitment to working alongside leading academic groups to tackle some of the most challenging cancers. About the ATOMIC study ATOMIC (A021502, NCT02912559 ) is a Phase III, randomized, open-label, multicenter study investigating the addition of Tecentriq ® (atezolizumab) to FOLFOX6 chemotherapy (a combination of folinic acid, fluorouracil, and oxaliplatin) in patients with stage III colon cancer who have a deficiency in DNA mismatch repair (dMMR). The trial enrolled 712 patients. Participants were randomized 1:1 to receive either FOLFOX6 plus Tecentriq for 12 cycles (six months) followed by Tecentriq monotherapy for 13 cycles (an additional six months), or FOLFOX6 alone for 12 cycles. The primary endpoint is disease-free survival (DFS). About Tecentriq ® (atezolizumab) Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells. Tecentriq has been approved for some of the most aggressive and difficult-to-treat forms of cancer, and is the first PD-(L)1 cancer immunotherapy available in both subcutaneous and intravenous formulations. What are Tecentriq and Tecentriq Hybreza? Tecentriq (atezolizumab) and Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) are prescription medicines used to treat: Adults with a type of lung cancer called non-small cell lung cancer (NSCLC). Tecentriq or Tecentriq Hybreza may be used alone as a treatment for your lung cancer: to help prevent your lung cancer from coming back after your tumor(s) has been removed by surgery and you have received platinum-based chemotherapy, and you have stage 2 to stage 3A NSCLC (talk to your healthcare provider about what these stages mean), and your cancer tests positive for “PD-L1”. Tecentriq or Tecentriq Hybreza may be used alone as your first treatment when your lung cancer: has spread or grown, and your cancer tests positive for “high PD-L1”, and your tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq or Tecentriq Hybreza may be used with the medicines bevacizumab, paclitaxel, and carboplatin as your first treatment when your lung cancer: has spread or grown, and is a type called “non-squamous NSCLC”, and your tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq or Tecentriq Hybreza may be used with the medicines paclitaxel protein-bound and carboplatin as your first treatment when your lung cancer: has spread or grown, and is a type called “non-squamous NSCLC”, and your tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq or Tecentriq Hybreza may be used alone when your lung cancer: has spread or grown, and you have tried chemotherapy that contains platinum, and it did not work or is no longer working. If your tumor has an abnormal “EGFR” or “ALK” gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working. Adults with a type of lung cancer called “extensive stage small cell lung cancer (SCLC)”, which is SCLC that has spread or grown Tecentriq or Tecentriq Hybreza may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment Tecentriq or Tecentriq Hybreza may be used with the medicine lurbinectedin as maintenance treatment when your lung cancer: has not progressed after first treatment with Tecentriq or Tecentriq Hybreza and the chemotherapy medicines carboplatin and etoposide. Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq or Tecentriq Hybreza may be used with the medicine bevacizumab when your liver cancer: has spread or cannot be removed by surgery, and you have not received other medicines by mouth or injection through your vein (IV) to treat your cancer. Adults with a type of skin cancer called melanoma. Tecentriq or Tecentriq Hybreza may be used with the medicines cobimetinib and vemurafenib when your melanoma: has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal “BRAF” gene. Your healthcare provider will perform a test to make sure this Tecentriq or Tecentriq Hybreza combination is right for you. Adults and children (12 years of age and older), with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq or Tecentriq Hybreza may be used when your sarcoma: has spread to other parts of the body or cannot be removed by surgery. Adults with a type of bladder cancer called muscle invasive bladder cancer (MIBC) that has spread into the muscle layer of the bladder but not to other parts of the body. Tecentriq or Tecentriq Hybreza may be used alone as a treatment for your bladder cancer: to help prevent your bladder cancer from coming back after your bladder has been removed by surgery, and small pieces of DNA from the tumor (called circulating tumor DNA [ctDNA]) were found in your blood, showing that cancer cells remain in the body (molecular residual disease). Your healthcare provider will perform a test to make sure that Tecentriq or Tecentriq Hybreza is right for you. It is not known if Tecentriq Hybreza is safe and effective when used: in children for the treatment of NSCLC, SCLC, HCC, melanoma or MIBC. It is not known if Tecentriq is safe and effective when used: in children younger than 2 years of age for the treatment of ASPS. in children for the treatment of NSCLC, SCLC, HCC, melanoma or MIBC. Important Safety Information Who should not receive Tecentriq Hybreza? Do not receive Tecentriq Hybreza if you are allergic to hyaluronidase or any of the ingredients in Tecentriq Hybreza What is the most important information about Tecentriq and Tecentriq Hybreza? Tecentriq and Tecentriq Hybreza can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during your treatment or even after your treatment has ended. Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Lung problems cough shortness of breath chest pain Intestinal problems diarrhea (loose stools) or more frequent bowel movements than usual stools that are black, tarry, sticky, or have blood or mucus severe stomach-area (abdomen) pain or tenderness Liver problems yellowing of your skin or the whites of your eyes severe nausea or vomiting pain on the right side of your stomach area (abdomen) dark urine (tea colored) bleeding or bruising more easily than normal Hormone gland problems headaches that will not go away or unusual headaches eye sensitivity to light eye problems rapid heartbeat increased sweating extreme tiredness weight gain or weight loss feeling more hungry or thirsty than usual urinating more often than usual hair loss feeling cold constipation your voice gets deeper dizziness or fainting changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems decrease in your amount of urine blood in your urine swelling of your ankles loss of appetite Skin problems rash itching skin blistering or peeling painful sores or ulcers in your mouth or your nose, throat, or genital area fever or flu-like symptoms swollen lymph nodes Problems can also happen in other organs. These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq or Tecentriq Hybreza. Call or see your healthcare provider right away for any new or worsening signs or symptoms, including: Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight Persistent or severe muscle pain or weakness, muscle cramps Low red blood cells, bruising Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: chills or shaking itching or rash flushing shortness of breath or wheezing dizziness feeling like passing out fever back or neck pain Rejection of a transplanted organ or tissue. Your healthcare provider should tell you what signs and symptoms you should report and monitor you depending on the type of organ or tissue transplant that you have had. Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Tecentriq or Tecentriq Hybreza. Your healthcare provider will monitor you for these complications. Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with Tecentriq or Tecentriq Hybreza. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Tecentriq or Tecentriq Hybreza if you have severe side effects. Before you receive Tecentriq or Tecentriq Hybreza, tell your healthcare provider about all of your medical conditions, including if you: have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus have received an organ or tissue transplant, including corneal transplant have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic) have received radiation treatment to your chest area have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome are pregnant or plan to become pregnant. Tecentriq and Tecentriq Hybreza can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Tecentriq or Tecentriq Hybreza. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with Tecentriq or Tecentriq Hybreza. You should use an effective method of birth control during your treatment and for at least 5 months after the last dose of Tecentriq or Tecentriq Hybreza. are breastfeeding or plan to breastfeed. It is not known if Tecentriq or Tecentriq Hybreza passes into your breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq or Tecentriq Hybreza. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of Tecentriq when used alone include: feeling tired or weak decreased appetite nausea cough shortness of breath The most common side effects of Tecentriq Hybreza when used alone include: feeling tired or weak muscle or bone pain cough shortness of breath decreased appetite The most common side effects of Tecentriq and Tecentriq Hybreza when used in lung cancer with other anti-cancer medicines include: feeling tired or weak nausea hair loss constipation diarrhea decreased appetite The most common side effects of Tecentriq and Tecentriq Hybreza when used in hepatocellular carcinoma (HCC) with bevacizumab include: high blood pressure feeling tired or weak too much protein in the urine The most common side effects of Tecentriq and Tecentriq Hybreza when used in melanoma with cobimetinib and vemurafenib include: skin rash joint, muscle, or bone pain feeling tired or weak liver injury fever nausea itching swelling of legs or arms mouth swelling (sometimes with sores) low thyroid hormone levels sunburn or sun sensitivity The most common side effect of Tecentriq and Tecentriq Hybreza when used alone in MIBC is: urinary tract infection Tecentriq and Tecentriq Hybreza may cause fertility problems in females, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility. These are not all the possible side effects of Tecentriq and Tecentriq Hybreza. Ask your healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq and Tecentriq Hybreza. You may report side effects to the FDA at 1-800-FDA-1088 or . You may also report side effects to Genentech at 1-888-835-2555. Please see full Prescribing Information for Tecentriq and Tecentriq Hybreza and the Medication Guides for Tecentriq and Tecentriq Hybreza for additional Important Safety Information. About Genentech Oncology For more than 30 years, Genentech has pioneered oncology breakthroughs and is working to build a future where people with cancer can thrive, in spite of their diagnosis. With our therapies, we are intercepting disease where there is potential to deliver the best outcomes, while striving for longer-term impact in hard-to-treat settings. Our therapies are designed for the real world—reducing treatment burden and ensuring innovative care reaches patients who need them most, wherever they are. By working in lockstep with the medical, scientific, and patient communities, we are shaping the next era of cancer care. About Genentech Founded 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit . Contacts Media Contact: Stella Belonwu (650) 467-6800 Advocacy Contact: Mychalleah Werner (650) 296-6218 Investor Contacts: Loren Kalm (650) 225-3217 Bruno Eschli +41 61 687 5284