Oxaliplatin

2026年Q1，全球11款ADC药物合计销售超40亿美元，同比增长近四成。Enhertu与Padcev双雄并立，增速惊人；而曾经的“ADC一姐”Kadcyla却连续下滑，罗氏面临换挡压力。新药Datroway、Trodelvy快速放量，适应症拓展与联合疗法正重新定义赛道格局。这场盛宴，谁在吃肉，谁在喝汤？2026年Q1全球ADC药物销售额概况 双雄争霸：Enhertu与Padcev的“加速度”密码 Enhertu（德曲妥珠单抗）作为HER2 ADC领域的后起之秀，2026年Q1以14.22亿美元（计入第一三共）的销售额稳居榜首，同比增长34%（阿斯利康单独统计为8.31亿美元），上市多年仍保持强劲增长势头，核心驱动力来自中国市场的密集获批与全球适应症的持续拓展。作为阿斯利康与第一三共合作的核心产品，Enhertu凭借其独特的DXd-ADC技术平台，具备药物抗体比高、旁观者效应强、半衰期长等优势，在HER2阳性肿瘤治疗中展现出卓越疗效，而2026年以来中国市场的适应症突破，成为其增长的关键引擎。 2026年1月22日，Enhertu获中国NMPA正式批准，用于既往接受过一种含曲妥珠单抗治疗方案的局部晚期或转移性HER2阳性成人胃或胃食管结合部腺癌患者；短短两个多月后，3月27日，其再获中国NMPA批准，序贯紫杉醇、曲妥珠单抗和帕妥珠单抗（THP），适用于HER2阳性II期（高危）或III期乳腺癌成人患者的新辅助治疗。中国作为全球最大的肿瘤市场之一，HER2阳性乳腺癌、胃癌患者基数庞大，这两项适应症的获批的快速打开了中国市场空间，为Enhertu的销售额增长注入强劲动力。 2026年3月9日，FDA基于DESTINY-Breast05 III期研究关键数据，授予Enhertu sBLA优先审评资格，用于新辅助治疗后仍有残留浸润性病变的HER2阳性早期乳腺癌患者，PDUFA日期定为2026年7月7日，同时EMA也已受理该申请；3月23日，其在日本获批二线治疗HER2阳性（IHC3+/2+ISH+）不可切除晚期/复发胃癌。从晚期到早期、从乳腺癌到胃癌，Enhertu的适应症布局不断完善，逐步覆盖肿瘤治疗的全周期，进一步放大其市场优势。 相较于Enhertu的“全面开花”，Padcev（恩诺单抗）的39%增长（2026年Q1销售额5.91亿美元）则聚焦于优势赛道的深度突破，核心动力来自III期EV-304研究的阳性结果与肌层浸润性膀胱癌（MIBC）适应症的拓展。Padcev是辉瑞与安斯泰来联合开发的Nectin-4 ADC药物，此前已在晚期尿路上皮癌领域占据一席之地，而MIBC适应症的突破，为其打开了全新的蓝海市场。 2026年2月，Padcev的III期EV-304研究取得阳性结果，该研究针对顺铂适合性肌层浸润性膀胱癌患者，结果显示Padcev治疗显著降低患者复发或死亡风险近50%，疗效优势显著，辉瑞就此向FDA提交sBLA并获得优先审评资格；早在2026年1月，基于EV-303试验结果，辉瑞已向日本厚生劳动省递交sNDA，用于治疗不适合顺铂化疗的MIBC患者。MIBC作为膀胱癌的高危亚型，临床治疗手段有限，Padcev的临床试验成功，不仅填补了该领域的治疗空白，更使其从晚期尿路上皮癌拓展至早期高危人群，市场空间大幅提升。 深入对比两者的核心策略，不难发现双雄争霸的底层逻辑差异，这也决定了其未来的登顶潜力。在适应症布局上，Enhertu走“广谱覆盖”路线，以HER2为核心，逐步拓展至乳腺癌、胃癌、肺癌等多个瘤种，覆盖早期、晚期等全治疗阶段，受众群体更广泛；Padcev则走“精准聚焦”路线，聚焦尿路上皮癌这一细分赛道，深耕MIBC等未满足临床需求领域，形成差异化优势。 在联合疗法布局上，Enhertu依托DXd-ADC平台的优势，积极探索与免疫治疗、靶向治疗的联合应用，目前已开展多项联合PD-1/PD-L1抑制剂的临床试验，试图进一步提升疗效、扩大适用人群；Padcev则更注重单药疗效的突破，通过关键临床试验数据巩固其在尿路上皮癌领域的地位，联合疗法的探索相对滞后。在区域市场策略上，Enhertu采取“全球同步推进”模式，尤其重视中国、日本等亚洲市场的拓展，通过密集获批适应症快速抢占市场；Padcev则先聚焦欧美、日本等成熟市场，中国市场的布局相对缓慢，目前尚未有适应症获批。 从长期来看，Enhertu的登顶概率更高：其HER2靶点覆盖瘤种广泛，中国等新兴市场的增长潜力巨大，且联合疗法的探索更具想象空间；而Padcev虽在尿路上皮癌领域优势明显，但赛道相对狭窄，若无法实现适应症的跨瘤种拓展，长期增长将面临瓶颈。双雄争霸的格局仍将持续，但Enhertu的领跑优势将进一步扩大。老将失速：Kadcyla下滑背后，罗氏的“接班人”浮出水面 与Enhertu、Padcev的高速增长形成鲜明对比的是，罗氏的Kadcyla（T-DM1）在2026年Q1交出了同比下滑4%的成绩单，销售额约5.59亿美元（4.39亿瑞士法郎），已连续多季度陷入增长停滞甚至下滑。作为全球首款获批的HER2 ADC，Kadcyla曾引领ADC行业的发展，如今却逐步跌落神坛，背后是多重因素的叠加，而罗氏也早已开始布局“接班人”，Polivy的崛起正逐步填补Kadcyla下滑留下的市场空白。 Kadcyla连续多季度下滑，核心原因有两点：一是市场竞争加剧，尤其是Enhertu的强势侵蚀；二是专利悬崖逼近，仿制药的冲击逐步显现。在HER2 ADC领域，Kadcyla曾是晚期HER2阳性乳腺癌的标准治疗药物，但Enhertu凭借更优的疗效、更低的毒性，逐步替代Kadcyla成为临床首选——多项头对头临床试验显示，Enhertu在客观缓解率、无进展生存期等关键指标上均优于Kadcyla，尤其在晚期乳腺癌患者中，Enhertu的疗效优势更为显著。随着Enhertu在欧美、中国等主要市场的适应症不断拓展，其持续抢占Kadcyla的市场份额，导致Kadcyla在欧美市场的销售额持续下滑。 Kadcyla的专利保护期逐步到期，专利悬崖的逼近进一步加剧了其下滑态势。目前，Kadcyla在欧美部分地区的专利已到期，仿制药陆续获批上市，仿制药的价格优势进一步压缩了原研药的市场空间；而在中国，Kadcyla也已被纳入医保目录，价格大幅下降，虽能提升患者可及性，但也进一步降低了其销售额与利润空间。多重压力下，Kadcyla的下滑已成为必然，罗氏也逐步减少对这款“老将”的依赖，转而扶持新的核心ADC产品。 在Kadcyla下滑的同时，罗氏的另一款ADC药物Polivy（泊洛妥珠单抗）却实现逆势增长，2026年Q1销售额达5.19亿美元（4.07亿瑞士法郎），已快速逼近Kadcyla，同比增长26%，成为罗氏ADC战略的“接班人”。Polivy之所以能实现逆势增长，核心在于其靶点差异化优势与适应症的持续拓展，尤其在中国市场的突破，为其增长注入了强劲动力。 Polivy是一款靶向CD79B的ADC药物，主要用于淋巴瘤的治疗，与Kadcyla的HER2靶点形成差异化布局，避开了HER2 ADC领域的激烈竞争。CD79B是B细胞表面的特异性标志物，在弥漫大B细胞淋巴瘤（DLBCL）等B细胞淋巴瘤中高表达，而DLBCL是最常见的非霍奇金淋巴瘤亚型，临床需求迫切，Polivy的靶点选择精准击中了这一未满足临床需求。 2026年3月13日，中国NMPA正式批准Polivy联合利妥昔单抗、吉西他滨和奥沙利铂治疗方案上市，用于不适合接受造血干细胞移植的复发或难治性弥漫大B细胞淋巴瘤（R/R DLBCL）成人患者。这一适应症的获批，快速打开了中国淋巴瘤市场，而中国DLBCL患者基数庞大，为Polivy的销售额增长提供了广阔空间。此外，Polivy在欧美市场的表现也稳步提升，逐步成为R/R DLBCL的标准治疗药物之一，进一步推动其销售额增长。 Polivy的崛起，背后是罗氏ADC战略的隐性转型——从过去依赖HER2单一靶点，转向多靶点组合布局。此前，罗氏的ADC布局高度依赖Kadcyla的HER2靶点，但随着Enhertu等竞品的崛起，单一靶点的风险逐步显现；如今，罗氏已构建起多靶点ADC矩阵，除了CD79B（Polivy），还布局了Trop2、Claudin 18.2等多个热门靶点，试图通过多靶点布局分散风险，抢占更多细分市场。 从当前趋势来看，Polivy有望在2026年超越Kadcyla，成为罗氏的核心ADC产品，甚至有望成为下一个十亿美元分子。一方面，DLBCL领域的市场空间广阔，Polivy的适应症仍有进一步拓展的可能，如一线治疗、联合免疫治疗等；另一方面，罗氏拥有成熟的临床研发与商业化团队，能够快速推进Polivy的全球布局，进一步提升其市场份额。随着罗氏ADC战略的逐步落地，Polivy将成为其在ADC市场竞争中的核心筹码。新势力崛起：TROP2内卷、FRα突围、联合疗法改写规则 头部双雄争霸、罗氏战略转型的同时，ADC市场的新势力也正在快速崛起，其中TROP2赛道的白热化内卷、FRα靶点的稳健突围，以及联合疗法的快速发展，正在改写ADC行业的竞争规则，推动ADC从“化疗替代”向“靶向联合治疗平台”转型，也孕育着下一个ADC王者的可能。 TROP2（滋养层细胞表面抗原2）是当前ADC领域最热门的靶点之一，赛道竞争日趋白热化，吉利德的Trodelvy与阿斯利康/第一三共的Datroway成为最具竞争力的两大玩家，两者在2026年Q1均展现出强劲的增长势头。吉利德的Trodelvy（戈沙妥珠单抗）作为TROP2 ADC的先行者，2026年Q1销售额达4.02亿美元，同比大涨37%，持续快速放量，核心动力来自临床数据的突破与适应症的拓展。 2026年1月21日，《新英格兰医学杂志》（NEJM）发表了Trodelvy联合PD-1抑制剂Keytruda的完整III期数据（ASCENT-04/KEYNOTE-D19研究），该研究针对PD-L1阳性（CPS≥10）、未接受过治疗的转移性三阴性乳腺癌（mTNBC）患者，对比Trodelvy联合Keytruda与化疗联合Keytruda的疗效。研究结果显示，Trodelvy联合Keytruda的疗效显著优于标准方案，客观缓解率、无进展生存期均实现显著提升，这一数据为Trodelvy的联合疗法布局奠定了坚实基础，也进一步扩大了其在TNBC领域的优势。 与Trodelvy相比，阿斯利康与第一三共合作的Datroway（德达博妥单抗）虽上市较晚，但增长势头迅猛，2026年Q1销售额达1.02亿美元（计入第一三共），其中阿斯利康单独统计为0.43亿美元，同比增长超10倍。Datroway的核心竞争力在于其精准的生物标志物驱动策略，2026年1月13日，全球首个前瞻性TROP2生物标志物III期临床试验（TROPION-Lung17）首例患者已完成入组并给药，该试验面向经治晚期非鳞非小细胞肺癌（NSCLC）患者，聚焦TROP2 NMR生物标志物阳性人群，试图通过生物标志物筛选，实现更精准的治疗，提升疗效。 除了TROP2赛道的内卷，FRα（叶酸受体α）靶点的Enhertu则实现了稳健突围，成为小众靶点商业化的成功典范。艾伯维的Elahere（米妥昔单抗）作为FRα ADC的代表，2026年Q1销售额达1.98亿美元，同比增长10.7%，虽增速不及TROP2 ADC，但展现出良好的稳定性。FRα在卵巢癌、子宫内膜癌等妇科肿瘤中高表达，而这些肿瘤领域的治疗手段相对有限，Elahere的获批填补了该领域的治疗空白，凭借其靶点特异性优势，逐步占据小众市场份额，验证了小众靶点ADC的商业化可行性。 值得关注的是，联合疗法的快速发展，正在改写ADC行业的竞争规则，推动ADC从“化疗替代”向“靶向联合治疗平台”转型。当前，ADC+免疫、ADC+ADC、ADC+靶向治疗等联合策略已成为行业研发热点，其中ADC+免疫的联合疗法最具潜力——ADC可通过杀伤肿瘤细胞释放肿瘤抗原，激活机体的免疫反应，与PD-1/PD-L1抑制剂形成协同效应，进一步提升疗效，扩大适用人群。除了Trodelvy联合Keytruda的研究，Enhertu、Padcev等头部产品也在积极探索联合免疫治疗，多项临床试验正在推进中。 最后 ADC赛道已从“有没有”进入“好不好”的淘汰赛。头部产品靠适应症扩张维持高增长，老牌选手面临迭代压力，新分子则试图用差异化和联合疗法弯道超车。2026年，40亿美元只是序幕，真正的排位赛，才刚刚开始。 信息来源：各企业官网；猎药人俱乐部 立即扫码加入药事纵横交流群

Primary results from the Phase II ARACOG (AFT-47) head-to-head trial evaluating NUBEQA ® (darolutamide) versus enzalutamide in men with metastatic and non-metastatic castration-resistant prostate cancer (CRPC) or metastatic hormone-sensitive prostate cancer (mHSPC) will be presented Bayer will also present data from across its oncology portfolio, including XOFIGO ® (radium-223 dichloride), HYRNUO ® (sevabertinib), VITRAKVI ® (larotrectinib), and STIVARGA ® (regorafenib) WHIPPANY, N.J.--(BUSINESS WIRE)--Bayer today announced that new data from studies across their oncology portfolio will be presented at the upcoming 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago from May 29–June 2. In total, 16 abstracts will be presented spanning multiple cancer types, including prostate cancers, breast cancer, lung cancers, salivary gland cancer, renal cell carcinoma and colorectal cancers, further supporting Bayer’s commitment to the research of treatments for cancers and encouraging scientific exchange. Primary results from the Phase II ARACOG (AFT-47) head-to-head trial evaluating NUBEQA® (darolutamide) versus enzalutamide in men with metastatic and non-metastatic castration-resistant prostate cancer (CRPC) or metastatic hormone-sensitive prostate cancer (mHSPC) will be presented as an oral abstract and are additionally featured in the ASCO 2026 Annual Meeting Press Program. Data from a subgroup post-hoc analysis of the investigational Phase III ARANOTE trial investigating prostate-specific antigen outcomes of NUBEQA plus androgen deprivation therapy (ADT) in patients with metastatic castration-resistant prostate cancer (mCSPC) will also be presented. NUBEQA is indicated in the U.S. for the treatment of adult patients with mCSPC, with and without docetaxel, and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).1 Presentations will also highlight data from two trials investigating the safety and efficacy of XOFIGO® (radium-223 dichloride). Results from the Phase II RADICAL IR-US (Alliance A031801) randomized trial evaluating XOFIGO plus cabozantinib in patients with renal cell carcinoma (RCC) with bone metastases (BM) will be presented as an oral abstract session. Data from the Phase II ETCTN 10302 trial investigating XOFIGO in combination with paclitaxel in patients with metastatic breast cancer will be presented as a poster session. XOFIGO is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.2 XOFIGO is not approved in this investigational indication in combination with enzalutamide. Details on selected abstracts from Bayer at the 2026 ASCO Annual Meeting follow: NUBEQA (darolutamide) Cognitive effects of darolutamide vs enzalutamide: Results of ARACOG (AFT-47), a randomized clinical trial from the Alliance for Clinical Trials in Oncology Abstract: 5005; May 30, 4:24 p.m.–4:36 p.m. CDT Abstract: 5005; May 30, 4:24 p.m.–4:36 p.m. CDT Prostate-specific antigen outcomes of darolutamide and androgen deprivation therapy in patient subgroups by age, comorbidities, and concomitant medications: ARANOTE post hoc analyses Abstract: 5103; May 31, 9:00 a.m.–12:00 p.m. CDT Abstract: 5103; May 31, 9:00 a.m.–12:00 p.m. CDT XOFIGO (radium-223 dichloride) A phase 2 randomized trial of radium-223 dichloride and cabozantinib in patients (pts) with renal cell carcinoma (RCC) with bone metastases (BM): RADICAL (Alliance A031801) Abstract: 4500; May 29, 2:45 p.m.–2:57 p.m. CDT Abstract: 4500; May 29, 2:45 p.m.–2:57 p.m. CDT ETCTN 10302: A randomized phase II trial of radium-223 dichloride in combination with paclitaxel in patients with bone metastatic breast cancer Abstract: 3096; May 30, 1:30 p.m.–4:30 p.m. CDT Abstract: 3096; May 30, 1:30 p.m.–4:30 p.m. CDT HYRNUO® (sevabertinib) SOHO-01: Updated safety and efficacy of sevabertinib in patients with advanced HER2-mutant non-small cell lung cancer (NSCLC) Abstract: 8622; May 31, 9:00 a.m.–12:00 p.m. CDT Abstract: 8622; May 31, 9:00 a.m.–12:00 p.m. CDT VITRAKVI® (larotrectinib) Efficacy and safety of larotrectinib in patients with non-primary central nervous system TRK fusion cancer: An updated analysis Abstract: 3145; May 30, 1:30 p.m.–4:30 p.m. CDT Abstract: 3145; May 30, 1:30 p.m.–4:30 p.m. CDT Precision oncology in practice: Real-world multicenter experience with larotrectinib in pediatric extracranial NTRK fusion–positive tumors Abstract: 10036; June 1, 1:30 p.m.–4:30 p.m. CDT Abstract: 10036; June 1, 1:30 p.m.–4:30 p.m. CDT STIVARGA® (regorafenib) Evaluation of the combination of regorafenib + avelumab in patients with HPV-associated cancer: The phase II REGOMUNE study Abstract: 2517; May 30, 8:42 a.m.-8:48 a.m. CDT Abstract: 2517; May 30, 8:42 a.m.-8:48 a.m. CDT About NUBEQA® (darolutamide)1 NUBEQA® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. NUBEQA was developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with: Non-metastatic castration-resistant prostate cancer (nmCRPC) Metastatic castration-sensitive prostate cancer (mCSPC) Metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel IMPORTANT SAFETY INFORMATION Warnings & Precautions Ischemic Heart Disease – Ischemic heart disease, including fatal cases, occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, ischemic heart disease occurred in 3.4% of patients receiving NUBEQA and 2.2% receiving placebo, including Grade 3-4 events in 1.4% and 0.3%, respectively. Ischemic events led to death in 0.4% of patients receiving NUBEQA and 0.4% receiving placebo. In ARASENS, ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel and 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% and 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel and 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease. Seizure – Seizure occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, Grade 1-3 seizure occurred in 0.2% of patients receiving NUBEQA. Seizure occurred from 261 to 665 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.8% of patients receiving NUBEQA with docetaxel, including two Grade 3 events. Seizure occurred from 38 to 1754 days after initiation of NUBEQA. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment. Embryo-Fetal Toxicity – The safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose. Adverse Reactions In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo. Fatal adverse reactions that occurred in ≥2 patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common (>2% with a ≥2% increase compared to placebo) adverse reactions, including laboratory test abnormalities, were increased AST (23%), decreased neutrophil count (20%), fatigue (16%), increased bilirubin (16%), pain in extremity (6%), and rash (4%). Clinically relevant adverse reactions occurring in 2% or more of patients treated with NUBEQA included ischemic heart disease (4%) and heart failure (2.1%). In ARANOTE, serious adverse reactions occurred in 24% of patients receiving NUBEQA. Serious adverse reactions in ≥1% of patients who received NUBEQA included pneumonia (2%), urinary tract infection (1.8%), musculoskeletal pain (1.6%), hemorrhage (1.6%), arrhythmias (1.3%), and spinal cord compression (1.1%). Fatal adverse reactions occurred in 4.7% of patients receiving NUBEQA and those that occurred in ≥2 patients included sepsis (1.1%), craniocerebral injury (0.4%), and myocardial infarction (0.4%). The most common (≥10% with a ≥2% increase compared to placebo) adverse reaction is urinary tract infection (12%). The most common laboratory test abnormalities (≥15% with a ≥5% increase over placebo) are increased AST (32%), increased ALT (28%), increased bilirubin (17%), and decreased neutrophil count (16%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA included arrhythmia (8.8%), pneumonia (3.6%), and myocardial infarction (0.7%). In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), neutrophil count decreased (2.8%), musculoskeletal pain (2.6%) and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel. Fatal adverse reactions in ≥2 patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common (≥10% with a ≥2% increase over placebo with docetaxel) adverse reactions are constipation (23%), rash (20%), decreased appetite (19%), hemorrhage (18%), increased weight (18%), and hypertension (14%). The most common laboratory test abnormalities (≥30%) are anemia (72%), hyperglycemia (57%), decreased lymphocyte count (52%), decreased neutrophil count (49%), increased AST (40%), increased ALT (37%), and hypocalcemia (31%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures (8%), ischemic heart disease (3.2%), seizures (0.6%), and drug-induced liver injury (0.3%). Drug Interactions Effect of Other Drugs on NUBEQA – Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers. Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed. Effects of NUBEQA on Other Drugs – NUBEQA is an inhibitor of BCRP transporter. Concomitant use of NUBEQA increases the AUC and Cmax of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. NUBEQA is an inhibitor of OATP1B1 and OATP1B3 transporters. Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor patients more frequently for adverse reactions of these drugs and consider dose reduction while patients are taking NUBEQA. Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA. For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information. Please see the full Prescribing Information. About XOFIGO® (radium-223 dichloride) Injection2 XOFIGO is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. Important Safety Information for XOFIGO® (radium-223 dichloride) Injection Warnings and Precautions: Bone Marrow Suppression: In the phase 3 ALSYMPCA trial, 2% of patients in the XOFIGO arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with XOFIGO bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the XOFIGO arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of XOFIGO-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with XOFIGO and placebo. Myelosuppression–notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia–has been reported in patients treated with XOFIGO. Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue XOFIGO in patients who experience life-threatening complications despite supportive care for bone marrow failure Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of XOFIGO. Prior to first administering XOFIGO, the absolute neutrophil count (ANC) should be ≥1.5 × 109/L, the platelet count ≥100 × 109/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 × 109/L and the platelet count ≥50 × 109/L. Discontinue XOFIGO if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care Concomitant Use With Chemotherapy: Safety and efficacy of concomitant chemotherapy with XOFIGO have not been established. Outside of a clinical trial, concomitant use of XOFIGO in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, XOFIGO should be discontinued Increased Fractures and Mortality in Combination With Abiraterone Plus Prednisone/Prednisolone: XOFIGO is not recommended for use in combination with abiraterone acetate plus prednisone/prednisolone outside of clinical trials. At the primary analysis of the Phase 3 ERA-223 study that evaluated concurrent initiation of XOFIGO in combination with abiraterone acetate plus prednisone/prednisolone in 806 asymptomatic or mildly symptomatic mCRPC patients, an increased incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received XOFIGO in combination with abiraterone acetate plus prednisone/prednisolone compared to patients who received placebo in combination with abiraterone acetate plus prednisone/prednisolone. Safety and efficacy with the combination of XOFIGO and agents other than gonadotropin-releasing hormone analogues have not been established Embryo-Fetal Toxicity: The safety and efficacy of XOFIGO have not been established in females. XOFIGO can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with XOFIGO Administration and Radiation Protection: XOFIGO should be received, used, and administered only by authorized persons in designated clinical settings. The administration of XOFIGO is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations Fluid Status: Dehydration occurred in 3% of patients on XOFIGO and 1% of patients on placebo. XOFIGO increases adverse reactions such as diarrhea, nausea, and vomiting, which may result in dehydration. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia Injection Site Reactions: Erythema, pain, and edema at the injection site were reported in 1% of patients on XOFIGO Secondary Malignant Neoplasms: XOFIGO contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223 dichloride, XOFIGO may increase the risk of osteosarcoma or other secondary malignant neoplasms. However, the overall incidence of new malignancies in the randomized trial was lower on the XOFIGO arm compared to placebo (<1% vs 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow-up for patients on the trial Subsequent Treatment With Cytotoxic Chemotherapy: In the randomized clinical trial, 16% of patients in the XOFIGO group and 18% of patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with XOFIGO will tolerate subsequent cytotoxic chemotherapy Adverse Reactions: The most common adverse reactions (≥10%) in the XOFIGO arm vs the placebo arm, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of XOFIGO-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the XOFIGO arm (≥10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%), leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%). Please see the full Prescribing Information for XOFIGO (radium Ra 223 dichloride). About HYRNUO (sevabertinib)3 HYRNUO is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. IMPORTANT SAFETY INFORMATION Warnings & Precautions Diarrhea HYRNUO can cause severe diarrhea that can lead to dehydration and electrolyte imbalances. In the pooled safety population, diarrhea was reported in 86% of patients who received HYRNUO including Grade 3 in 15%. The median time to first onset of any grade diarrhea was four days. Dosage interruptions occurred in 15% of patients, and dose reductions occurred in 12% of patients. At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide), and to increase their fluid and electrolyte intake. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity. Hepatotoxicity HYRNUO can cause severe hepatotoxicity characterized by elevations of liver function tests. In the pooled safety population, based on adverse reaction data, hepatotoxicity occurred in 24% of patients treated with HYRNUO including 3% Grade 3. Based on laboratory data, 35% of patients treated with HYRNUO experienced increased alanine aminotransferase (ALT), including 2.3% Grade 3. Increased aspartate aminotransferase (AST) occurred in 35% of patients treated with HYRNUO, including 2.3% Grade 3. Increased bilirubin occurred in 12% of patients treated with HYRNUO. The median time to first onset of AST or ALT elevation was 1.4 (range 0.2 to 14.5) months. HYRNUO was interrupted for an adverse reaction of hepatotoxicity in 4.1% of patients, the dose was reduced in 4.1% and permanently discontinued in 0.4%. Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to the first administration of HYRNUO, every 2 weeks for the first month and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose or permanently discontinue HYRNUO based on the severity of the adverse reaction. Interstitial Lung Disease/Pneumonitis HYRNUO can cause severe interstitial lung disease (ILD)/pneumonitis. In the pooled safety population, ILD/pneumonitis occurred in two patients (0.7%) treated with HYRNUO, including 0.4% Grade 3. One patient required interruption of HYRNUO. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis. Ocular Toxicity HYRNUO can cause ocular toxicity. In the pooled safety population, ocular toxicity occurred in 14% of patients treated with HYRNUO, including 11% Grade 1, 2.6% Grade 2 and 0.4% Grade 3 (one case of corneal epithelial microcysts with temporary unilateral blindness). Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity. Pancreatic Enzyme Elevation HYRNUO can cause elevations of amylase and lipase levels. In the pooled safety population, based on laboratory data, increased amylase occurred in 32% of patients treated with HYRNUO, including 3.2% Grade 3 or 4. Increased lipase elevation occurred in 40% of patients treated with HYRNUO, including 10% Grade 3 or 4. Two patients (0.7%) required interruption of HYRNUO due to increased lipase and three (1.1%) required interruption of HYRNUO due to increased amylase. The median time to onset of increased amylase/lipase was 1.4 months (range: 0.2 to 17 months). Monitor amylase and lipase regularly during treatment with HYRNUO. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity. Embryo-fetal toxicity Based on findings from animal studies and its mechanism of action, HYRNUO can cause fetal harm when administered to a pregnant woman. In embryo-fetal development studies, oral administration of sevabertinib to pregnant rats during the period of organogenesis resulted in alterations to growth at maternal exposures ≥0.18 times the human exposure based on area under the curve (AUC) at the clinical dose of 20 mg twice daily. Animal studies with disrupted or depleted HER2/EGFR and in vitro assays have demonstrated that inhibition of HER2 and/or EGFR results in structural abnormalities, alteration to growth, and embryo-fetal and infant mortality. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose. Adverse Reactions In SOHO-01 (Groups D and E), serious adverse reactions occurred in 31% of patients who received HYRNUO. Serious adverse reactions in ≥2% of patients were diarrhea (6%), pneumonia (3.7%), dyspnea (2.2%), and pleural effusion (2.2%). The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea (87%), rash (66%), paronychia (33%), stomatitis (29%), and nausea (21%). The most common Grade 3 and 4 laboratory abnormalities (≥2%) were potassium decreased (13%), lipase increased (12%), lymphocyte count decreased (6%), sodium decreased (4.4%), amylase increased (3.8%), aspartate aminotransferase (AST) increased (3%), and alanine aminotransferase (ALT) increased (3%). Laboratory abnormalities in <20% of patients who received HYRNUO include blood bilirubin increased (14%; all were Grades 1 or 2). Clinically relevant adverse reactions in <10% of patients who received HYRNUO included edema (8%), cardiac arrhythmia (6%; includes arrhythmia, atrioventricular block complete, electrocardiogram QT prolonged, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia) and alopecia (3.7%). Drug Interactions Effects of Other Drugs on HYRNUO - Sevabertinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor may increase sevabertinib plasma concentrations, which may increase the risk of HYRNUO adverse reactions. Monitor patients for increased HYRNUO-associated adverse reactions with moderate CYP3A inhibitors. Avoid concomitant use of HYRNUO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dose. Concomitant use with a strong or moderate CYP3A inducer may decrease sevabertinib plasma concentrations, which may decrease the effectiveness of HYRNUO. Avoid concomitant use of HYRNUO with strong or moderate CYP3A inducers. Effects of HYRNUO on Other Drugs – Sevabertinib is a weak to moderate CYP3A inhibitor. Sevabertinib increases exposure of CYP3A substrates, which may increase the risk of adverse reactions related to these substrates. Avoid concomitant use of HYRNUO with CYP3A substrates where minimal increases in the concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate. Sevabertinib is a P-gp inhibitor. Sevabertinib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information for P-gp substrates where minimal increases in the concentration may lead to serious adverse reactions. Sevabertinib is an inhibitor of CYP1A1 in vitro. Sevabertinib may increase exposure of CYP1A1 substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information of CYP1A1 substrates. Please see full Prescribing Information. About VITRAKVI® (larotrectinib)4 VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that: have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Select patients for therapy based on an FDA-approved test. IMPORTANT SAFETY INFORMATION Warnings and Precautions Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances. In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 40.3% with Grades 3-4 in 3.8% of patients. Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 6 months (range: 2 days to 56 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (4.1%), disturbance in attention (3.6%), confusional state (2.3%), cognitive disorder (1.6%), delirium (1.4%), and hallucination (1.1%). Grade 3 cognitive adverse reactions occurred in 1.8% of patients and Grade 4 cognitive adverse reactions in 0.2% of patients. Among the 49 patients with cognitive impairment, 6% required a dose modification and 18% required dose interruption. Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.3 months (range: 1 day to 65 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), agitation (3.2%), depression (3.2%), irritability (2.3%), and restlessness (1.1%). Grade 3 mood disorders occurred in 0.9% of patients. Among the 63 patients who experienced mood disorders, no patient required a dose modification, and 1.6% required dose interruption. Dizziness occurred in 22% of patients, and Grade 3 dizziness occurred in 0.9% of patients. Among the 96 patients who experienced dizziness, 6% of patients required a dose modification and 5% required dose interruption. Sleep disturbances occurred in 12% of patients. Sleep disturbances included insomnia (9%), somnolence (3.4%), and sleep disorder (0.5%). Grade 3 sleep disturbances occurred in 0.2% of patients. Among the 54 patients who experienced sleep disturbances, no patient required a dose modification and 3.7% required dose interruption. Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed. Skeletal Fractures: Skeletal fractures can occur in patients taking VITRAKVI. Among 444 patients who received VITRAKVI across clinical trials, fractures occurred in 7% of patients; 6% of 290 adult patients and 10% of 154 pediatric patients. Median time to first fracture was 13 months (range 27 days to 73 months) in patients followed per fracture. The most common fractures were of the rib (1.4%), fibula, foot or wrist (0.7% each). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients. Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures. Hepatotoxicity: Hepatotoxicity including drug induced liver injury (DILI) has occurred in patients taking VITRAKVI. In patients who received VITRAKVI (n=444), increased AST of any grade occurred in 62% of patients and increased ALT of any grade occurred in 61%. Grade 3-4 increased AST or ALT occurred in 7% and 8% of patients, respectively. The median time to onset of increased AST was 1.9 months (range: 4 days to 3.8 years). The median time to onset of increased ALT was 1.9 months (range: 1 day to 4.9 years). Increased AST and ALT leading to dose modifications occurred in 1.6% and 3.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 4 (0.9%) patients. There have been reports from clinical studies and postmarketing cases of Grade ≥ 2 increases in ALT and/or AST with increases in bilirubin ≥ 2 x ULN. Obtain liver function tests (ALT, AST, ALP and bilirubin) before initiation of VITRAKVI and monitor every 2 weeks during the first 2 months of treatment, then monthly thereafter, or more frequently following the occurrence of Grade 2 or greater AST or ALT elevation. Temporarily withhold, reduce the dose, or permanently discontinue VITRAKVI based on severity. Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the last dose of VITRAKVI. Adverse Reactions The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased AST (62%), increased ALT (61%), anemia (45%), hypoalbuminemia (44%), musculoskeletal pain (41%), increased alkaline phosphatase (40%), leukopenia (37%), lymphopenia (35%), neutropenia (34%), hypocalcemia (32%), fatigue (31%), vomiting (30%), cough (29%), constipation (27%), pyrexia (26%), diarrhea (26%), nausea (25%), abdominal pain (24%), dizziness (22%), and rash (21%). Drug Interactions Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs. For coadministration with moderate CYP3A4 inhibitors, monitor for adverse reactions more frequently and reduce the dosage based on severity. For coadministration with moderate CYP3A4 inducers, modify dose as recommended. Use in Specific Populations Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the last dose. For important risk and use information about VITRAKVI, please see the full Prescribing Information. About STIVARGA® (regorafenib)5 STIVARGA is indicated for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. STIVARGA is indicated for the treatment of adult patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate. STIVARGA is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. IMPORTANT SAFETY INFORMATION WARNING: HEPATOTOXICITY Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue STIVARGA for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence. Hepatotoxicity: Severe drug-induced liver injury with fatal outcome occurred in STIVARGA-treated patients in clinical trials. In most cases, liver dysfunction occurred within the first 2 months of therapy and was characterized by a hepatocellular pattern of injury. Additionally, hyperammonemic encephalopathy, including fatal cases, has been reported in the postmarketing setting in patients treated with STIVARGA. The risk of hyperammonemic encephalopathy appears increased in patients with liver dysfunction, liver metastases, or primary liver cancer. In the metastatic CRC study, fatal hepatic failure occurred in 1.6% of patients in the regorafenib arm and in 0.4% of patients in the placebo arm. In the GIST study, fatal hepatic failure occurred in 0.8% of patients in the regorafenib arm. In the HCC study, there was no increase in the incidence of fatal hepatic failure as compared to placebo. Liver Function Monitoring: Obtain liver function tests (ALT, AST, and bilirubin) before initiation of STIVARGA and monitor at least every 2 weeks during the first 2 months of treatment. Thereafter, monitor monthly or more frequently as clinically indicated. Monitor liver function tests weekly in patients experiencing elevated liver function tests until improvement to less than 3 times the ULN or baseline. For patients who develop unexplained lethargy or changes in mental status, measure ammonia level and initiate appropriate clinical management. Temporarily hold and then reduce or permanently discontinue STIVARGA depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis. If hyperammonemic encephalopathy is confirmed, withhold and consider permanent discontinuation of STIVARGA. Infections: STIVARGA caused an increased risk of infections. The overall incidence of infection (Grades 1-5) was higher (32% vs 17%) in 1142 STIVARGA-treated patients as compared to the control arm in randomized, placebo-controlled trials. The incidence of Grade 3 or greater infections in STIVARGA-treated patients was 9%. The most common infections were urinary tract infections (5.7%), nasopharyngitis (4.0%), mucocutaneous and systemic fungal infections (3.3%), and pneumonia (2.6%). Fatal outcomes caused by infection occurred more often in patients treated with STIVARGA (1.0%) as compared to patients receiving placebo (0.3%); the most common fatal infections were respiratory (0.6% vs 0.2%). Withhold STIVARGA for Grade 3 or 4 infections, or worsening infection of any Grade. Resume STIVARGA at the same dose following resolution of infection. Hemorrhage: STIVARGA caused an increased incidence of hemorrhage. The overall incidence (Grades 1-5) was 18.2% in 1142 patients treated with STIVARGA vs 9.5% with placebo in randomized, placebo-controlled trials. The incidence of Grade 3 or greater hemorrhage in patients treated with STIVARGA was 3.0%. The incidence of fatal hemorrhagic events was 0.7%, involving the central nervous system or the respiratory, gastrointestinal, or genitourinary tracts. Permanently discontinue STIVARGA in patients with severe or life-threatening hemorrhage and monitor INR levels more frequently in patients receiving warfarin. Gastrointestinal Perforation or Fistula: Gastrointestinal perforation occurred in 0.6% of 4518 patients treated with STIVARGA across all clinical trials of STIVARGA administered as a single agent; this included 8 fatal events. Gastrointestinal fistula occurred in 0.8% of patients treated with STIVARGA and in 0.2% of patients in the placebo arm across randomized, placebo-controlled trials. Permanently discontinue STIVARGA in patients who develop gastrointestinal perforation or fistula. Dermatological Toxicity: In randomized, placebo-controlled trials, adverse skin reactions occurred in 71.9% of patients in the regorafenib arm and in 25.5% of patients in the placebo arm, including hand-foot skin reaction (HFSR) also known as palmar-plantar erythrodysesthesia syndrome (PPES) and severe rash, requiring dose modification. In the randomized, placebo-controlled trials, the overall incidence of HFSR was higher in 1142 STIVARGA-treated patients (53% vs 8%) than in the placebo-treated patients. Most cases of HFSR in STIVARGA-treated patients appeared during the first cycle of treatment. The incidences of Grade 3 HFSR (16% vs <1%), Grade 3 rash (3% vs <1%), serious adverse reactions of erythema multiforme (<0.1% vs 0%), and Stevens-Johnson syndrome (<0.1% vs 0%) were higher in STIVARGA-treated patients. Across all trials, a higher incidence of HFSR was observed in Asian patients treated with STIVARGA (all grades: 72%; Grade 3: 18%). Toxic epidermal necrolysis occurred in 0.02% of 4518 STIVARGA-treated patients across all clinical trials of STIVARGA administered as a single agent. Withhold STIVARGA, reduce the dose, or permanently discontinue depending on the severity and persistence of dermatologic toxicity. Hypertension: Hypertensive crisis occurred in 0.2% in STIVARGA-treated patients and in none of the patients in placebo arm across all randomized, placebo-controlled trials. STIVARGA caused an increased incidence of hypertension (30% vs 8% in metastatic CRC, 59% vs 27% in GIST, and 31% vs 6% in HCC). The onset of hypertension occurred during the first cycle of treatment in most patients who developed hypertension (67% in randomized, placebo-controlled trials). Do not initiate STIVARGA until blood pressure is adequately controlled. Monitor blood pressure weekly for the first 6 weeks of treatment and then every cycle, or more frequently, as clinically indicated. Temporarily or permanently withhold STIVARGA for severe or uncontrolled hypertension. Cardiac Ischemia and Infarction: STIVARGA increased the incidence of myocardial ischemia and infarction (0.9% with STIVARGA vs 0.2% with placebo) in randomized placebo-controlled trials. Withhold STIVARGA in patients who develop new or acute onset cardiac ischemia or infarction, and resume only after resolution of acute cardiac ischemic events if the potential benefits outweigh the risks of further cardiac ischemia. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristics finding on MRI, occurred in one of 4800 STIVARGA-treated patients across all clinical trials. Perform an evaluation for RPLS in any patient presenting with seizures, severe headache, visual disturbances, confusion, or altered mental function. Discontinue STIVARGA in patients who develop RPLS. Wound Healing Complications: Impaired wound healing complications can occur in patients who receive drugs that inhibit the VEGF signaling pathway. Therefore, STIVARGA has the potential to adversely affect wound healing. Withhold STIVARGA for at least 2 weeks prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of STIVARGA after resolution of wound healing complications has not been established. Embryo-Fetal Toxicity: STIVARGA can cause fetal harm when administered to a pregnant woman. There are no available data on STIVARGA use in pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with STIVARGA and for 2 months after the final dose. Nursing Mothers: Because of the potential for serious adverse reactions in breastfed infants from STIVARGA, do not breastfeed during treatment with STIVARGA and for 2 weeks after the final dose. Most Frequently Observed Adverse Drug Reactions in mCRC (≥30%): The most frequently observed adverse drug reactions (≥30%) in STIVARGA-treated patients vs placebo-treated patients in mCRC, respectively, were: asthenia/fatigue (64% vs 46%), pain (59% vs 48%), decreased appetite and food intake (47% vs 28%), HFSR/PPE (45% vs 7%), diarrhea (43% vs 17%), mucositis (33% vs 5%), weight loss (32% vs 10%), infection (31% vs 17%), hypertension (30% vs 8%), and dysphonia (30% vs 6%). Most Frequently Observed Adverse Drug Reactions in GIST (≥30%): The most frequently observed adverse drug reactions (≥30%) in STIVARGA-treated patients vs placebo-treated patients in GIST, respectively, were: HFSR/PPE (67% vs 12%), pain (60% vs 55%), hypertension (59% vs 27%), asthenia/fatigue (52% vs 39%), diarrhea (47% vs 9%), mucositis (40% vs 8%), dysphonia (39% vs 9%), infection (32% vs 5%), decreased appetite and food intake (31% vs 21%), and rash (30% vs 3%). Most Frequently Observed Adverse Drug Reactions in HCC (≥30%): The most frequently observed adverse drug reactions (≥30%) in STIVARGA-treated patients vs placebo-treated patients in HCC, respectively, were: pain (55% vs 44%), HFSR/PPE (51% vs 7%), asthenia/fatigue (42% vs 33%), diarrhea (41% vs 15%), hypertension (31% vs 6%), infection (31% vs 18%), decreased appetite and food intake (31% vs 15%). For important risk and use information, please see the full Prescribing Information including the Boxed Warning. About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes seven marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2025, the Group employed around 88,000 people and had sales of 45.6 billion euros. R&D expenses amounted to 5.8 billion euros. For more information, go to www.bayer.com. ©2026 Bayer BAYER, the Bayer Cross, NUBEQA, HYRNUO, VITRAKVI, STIVARGA, and XOFIGO are registered trademarks of Bayer. Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.