pembrolizumab

派姆单抗
  • 文章类型: Case Reports
    肺泡软组织肉瘤(ASPS)是一种罕见的恶性肿瘤,表现为生长缓慢的软组织肿块,常伴有远处转移。预后是可变的,转移性疾病完全缓解的报道很少。我们的患者在17岁时被诊断为转移性ASPS,原发性前臂病变并转移到肺部。她接受了前臂肿块的手术切除,然后辅助化疗和放疗靶向肺转移。在接下来的十年里,她有一个复杂的治疗过程。尽管接受了舒尼替尼治疗,但她的疾病仍在缓慢进展,帕唑帕尼,以及多西他赛和吉西他滨的组合。我们最终用免疫检查点抑制剂(ICIs)治疗她。Pembrolizumab,最初与贝伐单抗联合使用,后来作为单药治疗,导致显著的肿瘤缩小,尤其是肺部病变,在头三个月内。随后的影像学报告在15个月内完全缓解,并且在她的三年随访中没有疾病复发。我们的病例突出了极少数报道的在ICIs治疗后转移性ASPS完全缓解的病例之一。ICI可以为晚期ASPS的疾病缓解提供希望,一种罕见的恶性肿瘤,过去证明很难成功治疗。需要进行更多的研究来进一步评估疗效和成功治疗的任何相关预测因素。
    Alveolar soft part sarcoma (ASPS) is a rare malignant tumor that manifests as a slow-growing soft tissue mass and frequently presents with distant metastasis. The prognosis is variable, and complete remission of metastatic disease has rarely been reported. Our patient was diagnosed with metastatic ASPS at the age of 17, with a primary forearm lesion and metastasis to the lungs. She underwent surgical resection of her forearm mass, followed by adjuvant chemotherapy and radiation to target the lung metastasis. Over the next decade, she had a complicated course of treatment. Her disease continued to slowly progress despite treatment with sunitinib, pazopanib, and a combination of docetaxel and gemcitabine. We eventually treated her with immune checkpoint inhibitors (ICIs). Pembrolizumab, initially in combination with bevacizumab and later as monotherapy, resulted in significant tumor shrinkage, especially in the pulmonary lesions, within the first three months. Subsequent imaging reported complete remission within 15 months and no disease recurrence at her three-year follow-up. Our case highlights one of the very few reported cases of complete remission achieved in metastatic ASPS after treatment with ICIs. ICIs could offer hope for disease remission in advanced ASPS, a rare malignancy that has proven difficult to treat successfully in the past. More studies need to be conducted to further evaluate the efficacy and any associated predictors of successful treatment.
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  • 文章类型: Editorial
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  • 文章类型: Case Reports
    免疫检查点抑制剂(ICIs)显着改善许多恶性肿瘤的预后,但以许多副作用为代价。这可能会限制他们的利益。与免疫检查点抑制剂相关的急性肾损伤最常见的是急性肾小管间质性肾炎(ATIN),但也有各种肾小球肾炎病例的报道。在这里,我们报告了1例与ICIs相关的严重IgA肾病(IgAN),并进行了文献复习。IgAN在ICIs开始后5个月(范围1-12个月)的中位时间内被诊断出,具有不同的严重性,通常接受皮质类固醇和停用ICIs治疗。与我们的情况相反,文献中的肾脏结局通常是有利的,治疗后肾功能恢复和蛋白尿减少。尽管与ICIs相关的IgAN比ATIN罕见得多,它可能仍然被诊断不足。在使用ICIs之前,应仔细询问和筛查无症状性血尿。
    Immune checkpoint inhibitors (ICIs) dramatically improve the prognosis of many malignancies but at the cost of numerous side effects, which may limit their benefits. Acute kidney injury associated with immune checkpoint inhibitors most frequently are acute tubulointerstitial nephritis (ATIN), but various cases of glomerulonephritis have also been reported. Herein, we report a case of severe IgA nephropathy (IgAN) associated with ICIs and carry out a literature review. IgAN was diagnosed in a median time of 5 months (range 1-12 months) after the initiation of ICIs, with heterogeneous severity, and usually treated by corticosteroid and discontinuation of ICIs. In contrast to our case, renal outcomes in literature were often favorable, with recovery of renal function and a reduction in proteinuria on treatment. Although IgAN related to ICIs is a much rarer complication than ATIN, it may still be underdiagnosed. Careful questioning and screening for asymptomatic hematuria should be performed before using ICIs.
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  • 文章类型: Journal Article
    背景:Pembrolizumab与胃炎的发展有关,但其临床特征尚未明确。探讨派姆单抗致胃炎的临床特点,为胃炎的防治提供参考。
    方法:通过检索从开始到2023年9月30日的数据库,回顾性分析与pembrolizumab诱导的胃炎相关的病例报告和病例系列。
    结果:39例胃炎患者进入研究,中位年龄为63岁(范围34,81)。给药后,胃炎的中位时间为11.1个月(范围0.3、60)和7个周期(范围1、27)。上腹痛(24例,61.5%),恶心(17例,43.6%),呕吐(16例,41.0%)是最常见的主诉症状。食管胃十二指肠镜检查主要表现为红斑(16例,41.0%),出血(14例,35.9%)和糜烂(11例,28.2%)。胃粘膜活检显示慢性活动性胃炎伴淋巴细胞浸润。这些患者的症状和胃粘膜在接受全身性类固醇和质子泵抑制剂治疗后得到改善或恢复,无论派姆单抗是否停用。这些患者的症状和胃粘膜在全身类固醇治疗后得到改善或恢复,质子泵抑制剂,和生物制剂。
    结论:胃炎是pembrolizumab极为罕见的不良反应。当接受pembrolizumab的患者抱怨腹部症状时,内窥镜检查,组织活检,应积极进行免疫组织化学染色,以早期识别和诊断胃炎。
    BACKGROUND: Pembrolizumab is associated with the development of gastritis, but its clinical features have not been characterized. To explore the clinical features of pembrolizumab induced gastritis and provide reference for the prevention and treatment of gastritis.
    METHODS: Case reports and case series related to pembrolizumab induced gastritis were retrospectively analyzed by searching the database from inception to September 30, 2023.
    RESULTS: Thirty-nine patients with gastritis entered the study with a median age of 63 years (range 34, 81). The median time to gastritis was 11.1 months (range 0.3, 60) and 7 cycles (range 1, 27) after administration. Epigastric pain (24 cases, 61.5%), nausea (17 cases, 43.6%), and vomiting (16 cases, 41.0%) were the most frequently complained symptoms. Esophagogastroduodenoscopy mainly showed erythematous (16 cases, 41.0%), hemorrhage (14 cases, 35.9%) and erosions (11 cases, 28.2%). Gastric mucosal biopsy shows chronic active gastritis with lymphocytic infiltration. These patients\' symptoms and gastric mucosa improved or recovered after receiving systemic steroid and proton pump inhibitor therapy regardless of whether pembrolizumab was discontinued. These patients\' symptoms and gastric mucosa improved or recovered after treatment with systemic steroids, proton pump inhibitors, and biological agents.
    CONCLUSIONS: Gastritis is an extremely rare adverse effect of pembrolizumab. When patients receiving pembrolizumab complain of abdominal symptoms, endoscopy, tissue biopsy, and immunohistochemical staining should be actively performed for early identification and diagnosis of gastritis.
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  • 文章类型: Case Reports
    背景:转移性胰腺导管腺癌(PDAC)是一种致死性恶性肿瘤,生存数据令人沮丧。免疫治疗是许多癌症类型的一种有前途的方法,但由于其免疫抑制性肿瘤微环境,在晚期PDAC中取得了较差的疗效。我们描述了一例用pembrolizumab有效治疗的转移性PDAC病例。
    方法:我们报告了一例67岁女性,患有不可切除的局部晚期PDAC,接受吉西他滨+nab-紫杉醇治疗,然后接受放疗+卡培他滨。九个月时,在肝门水平观察到胰腺肿瘤进展,并出现新的肺结节,提示第二次原发性,经左肺活检证实。然后用pembrolizumab开始全身免疫疗法,一种针对程序性细胞死亡蛋白1的免疫检查点抑制剂,涵盖两种肿瘤类型。患者表现出在整个治疗过程中维持的完全代谢反应。自免疫疗法开始以来,患者在5.6年仍无疾病。
    结论:这些结果表明,放化疗后给予派姆单抗对转移性PDAC患者具有有益作用。据我们所知,这是首例报道的转移性PDAC和转移性肺癌患者在pembrolizumab治疗后未进行治愈性手术后表现出如此持久的完全缓解.需要进一步的研究来确定识别PDAC患者最有可能从这种免疫疗法中受益的生物标志物。
    BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with dispiriting survival data. Immunotherapy is a promising approach to many cancer types, but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment. We describe a case of metastatic PDAC effectively treated with pembrolizumab.
    METHODS: We report the case of a 67-year-old woman with unresectable locally advanced PDAC, treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine. At nine months, pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary, confirmed by left lung biopsy. Systemic immunotherapy was then initiated with pembrolizumab, an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types. The patient showed a complete metabolic response that was maintained throughout the treatment. The patient continues to be disease-free at 5.6 years since the start of immunotherapy.
    CONCLUSIONS: These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC. To our knowledge, this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery. Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.
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  • 文章类型: Journal Article
    癌症免疫疗法大大推进了肿瘤学领域,为各种恶性肿瘤提供新的治疗策略,包括乳腺癌.程序性细胞死亡蛋白1/程序性细胞死亡配体1(PD-1/PD-L1)途径在免疫调节中至关重要,及其抑制剂已证明在多种肿瘤中具有治疗益处。这篇综述旨在批判性地审视这一角色,临床疗效,安全,以及PD-1/PD-L1抑制剂在乳腺癌治疗中的未来方向,专注于pembrolizumab,Nivolumab,和tislelizumab,并阐明这一动态领域的挑战和前景。
    进行了全面的文献检索,遵守叙事审查报告清单,以实现透明报告。对选定研究的数据进行定性分析,以综合与作用机制相关的关键发现,临床应用,以及PD-1/PD-L1抑制剂在乳腺癌中的挑战。
    PD-1抑制剂在各种恶性肿瘤中显示出显着的疗效,包括晚期三阴性乳腺癌(TNBC),在那里,他们已经与化疗和新辅助/辅助治疗相结合进行了研究。这些抑制剂在其他乳腺癌亚型中的探索,例如人类表皮生长因子受体阳性和激素受体阳性的乳腺癌,正在进行中。该评论强调了患者选择方面的挑战,免疫相关不良事件(irAE)的管理,以及抗性机制的出现。它强调了需要持续的研究,重点是确定可靠的预测性生物标志物,阐明抗性机制,优化治疗策略。
    PD-1/PD-L1抑制剂在推进乳腺癌治疗方面具有重要的前景。这篇综述提供了重要的见解,并强调了持续科学探索以完善患者选择标准的临床重要性。改善治疗结果,扩大免疫治疗在乳腺癌中的应用。为了克服现有的挑战并实现这些抑制剂在乳腺癌和其他恶性肿瘤中的全部治疗潜力,进一步的研究势在必行。
    UNASSIGNED: Cancer immunotherapy has significantly advanced the field of oncology, providing novel therapeutic strategies for various malignancies, including breast cancer. The programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway is pivotal in immune regulation, and its inhibitors have demonstrated therapeutic benefits in diverse tumors. This review aims to critically examine the role, clinical efficacy, safety, and future directions of PD-1/PD-L1 inhibitors in breast cancer treatment, with a focus on pembrolizumab, nivolumab, and tislelizumab, and to elucidate the challenges and prospects in this dynamic field.
    UNASSIGNED: A comprehensive literature search was conducted, adhering to Narrative Review reporting checklist for transparent reporting. Data from selected studies were qualitatively analyzed to synthesize key findings related to the mechanisms of action, clinical applications, and challenges of PD-1/PD-L1 inhibitors in breast cancer.
    UNASSIGNED: PD-1 inhibitors have shown remarkable efficacy in various malignancies, including advanced triple-negative breast cancer (TNBC), where they have been investigated both in combination with chemotherapy and as neoadjuvant/adjuvant treatment. The exploration of these inhibitors in other breast cancer subtypes, such as human epidermal growth factor receptor-positive and hormone receptor-positive breast cancer, is ongoing. The review highlights the challenges in patient selection, management of immune-related adverse events (irAEs), and the emergence of resistance mechanisms. It underscores the need for ongoing research focusing on identifying reliable predictive biomarkers, elucidating mechanisms of resistance, and optimizing treatment strategies.
    UNASSIGNED: PD-1/PD-L1 inhibitors hold substantial promise in advancing breast cancer treatment. This review provides critical insights and emphasizes the clinical importance of continued scientific exploration to refine patient selection criteria, improve treatment outcomes, and expand the applications of immunotherapy in breast cancer. Further research is imperative to overcome the existing challenges and realize the full therapeutic potential of these inhibitors in breast cancer and other malignancies.
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  • 文章类型: Journal Article
    三阴性乳腺癌(TNBC)代表了一种高度侵袭性的乳腺癌亚型,历史上使用主要涉及蒽环类和紫杉烷类的化疗方案进行管理,产生不利的预后。这篇综述致力于全面检查早期三阴性乳腺癌(eTNBC)的治疗策略的现状。特别强调免疫治疗方式,联合疗法,预测性生物标志物,和正在进行的临床试验。这篇综述的主要目的是仔细评估现有文献,确定重大发现,并参与讨论它们对未来研究工作的潜在影响,临床应用,和政策制定。
    这项审查是使用PubMed和GoogleScholar数据库进行的,最新更新于2023年3月进行。搜索策略旨在确保对文献进行全面分析,专注于最近的进步。
    我们严格评估当前的eTNBC治疗前景,涵盖单一疗法的疗效和局限性,联合疗法,和预测性生物标志物。我们强调了最近试验的有希望的结果,解决围绕化疗的争议,并探索辅助和新辅助治疗(NAT)的最佳方法。对个性化治疗策略的见解,正在进行的试验,并提供了未来的前景,推进我们对eTNBC治疗方案的理解。
    通过对文献的综合分析,这篇综述强调了免疫治疗的潜力,特别是联合化疗,作为治疗eTNBC的一种有希望的方法。然而,需要进一步的研究来优化治疗策略,完善患者选择标准,并确定可靠的生物标志物,以预测对免疫检查点抑制剂(ICI)的反应。这篇综述的发现对未来的研究具有重要意义,临床实践,和政策制定,提供对eTNBC治疗当前挑战和进步的宝贵见解。最终,这些知识有助于改善患者的预后,提高生活质量,以及开发更有效的eTNBC治疗方法。
    UNASSIGNED: Triple negative breast cancer (TNBC) represents a highly aggressive breast cancer subtype, historically managed with chemotherapy regimens predominantly involving anthracyclines and taxanes, yielding unfavorable prognoses. This review endeavors to offer a thorough examination of the present state of treatment strategies for early stage triple negative breast cancer (eTNBC), with a particular emphasis on immunotherapy modalities, combination therapies, predictive biomarkers, and ongoing clinical trials. The principal aim of this review is to meticulously assess the available literature, ascertain significant discoveries, and engage in discussions regarding their potential implications for future research endeavors, clinical applications, and policy formulation.
    UNASSIGNED: This review was conducted using PubMed and Google Scholar databases, with the latest update performed in March 2023. The search strategy was designed to ensure a comprehensive analysis of the literature, with a focus on recent advancements.
    UNASSIGNED: We critically assess the current eTNBC treatment landscape, covering efficacy and limitations of monotherapy, combination therapies, and predictive biomarkers. We highlight promising results from recent trials, address controversies surrounding chemotherapy, and explore optimal approaches for adjuvant and neoadjuvant therapy (NAT). Insights into personalized treatment strategies, ongoing trials, and future perspectives are provided, advancing our understanding of therapeutic options for eTNBC.
    UNASSIGNED: Through a comprehensive analysis of the literature, this review highlights the potential of immunotherapy, particularly in combination with chemotherapy, as a promising approach for treating eTNBC. However, further research is warranted to optimize treatment strategies, refine patient selection criteria, and identify reliable biomarkers for predicting response to immune checkpoint inhibitors (ICIs). The findings of this review hold significant implications for future research, clinical practice, and policy-making, offering valuable insights into the current challenges and advancements in eTNBC treatment. Ultimately, this knowledge can contribute to improved patient outcomes, enhanced quality of life, and the development of more effective therapeutic approaches for eTNBC.
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  • 文章类型: Journal Article
    背景:该研究评估了pembrolizumab在转移性非小细胞肺癌(mNSCLC)中的一线应用,头颈部鳞状细胞癌(HNSCC),胃癌,和肾细胞癌。利用欧洲医学肿瘤学会临床获益量表(ESMO-MCBS)和美国临床肿瘤学会价值框架(ASCO-VF),该分析结合了来自关键KEYNOTE试验的数据。
    方法:该研究通过9项随机对照试验系统地评估了派博利珠单抗在晚期实体恶性肿瘤中的临床获益。其中一个由两个实验臂组成。主要来源的数据提取来自PubMed,ASCO,和ESMO出版物。利用ESMO-MCBS和ASCO-VF形式,评估侧重于临床效益,毒性,和奖励积分,通过协商一致的讨论解决了差异。
    结果:在2018年至2023年之间,pembrolizumab的9个一线适应症获得了食品药品监督管理局批准用于转移性实体瘤。ESMO-MCBS等级的显着差异表明,有7项试验具有实质性的临床益处(5至4级),有3项试验具有中等至可忽略的益处(3至1级)。奖励积分,主要基于曲线的尾部,被分配给三项总生存期试验,一个是无进展生存期,和一个显着改善生活质量。
    结论:我们对pembrolizumab在不同癌症中的评估,尤其是在mNSCLC和HNSCC中,在临床益处解释中揭示了不同的结果和挑战。临床获益的评估,结合定量和定性端点,强调需要考虑生存结果和患者观点,以便全面理解。
    BACKGROUND: The study evaluates the first-line application of pembrolizumab in metastatic non-small-cell lung cancer (mNSCLC), head and neck squamous cell cancer (HNSCC), gastric cancer, and renal cell carcinoma. Utilizing the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the American Society of Clinical Oncology Value Framework (ASCO-VF), the analysis incorporates data from pivotal KEYNOTE trials.
    METHODS: The study systematically assessed the clinical benefit of pembrolizumab in advanced solid malignancies through nine randomized controlled trials, one of which comprised two experimental arms. Data extraction from primary sources was conducted from PubMed, ASCO, and ESMO publications. Utilizing ESMO-MCBS and ASCO-VF forms, the evaluation focused on clinical benefit, toxicity, and bonus points, with discrepancies resolved through consensus discussions.
    RESULTS: Nine first-line indications for pembrolizumab received Food and Drug Administration approval for metastatic solid tumors between 2018 and 2023. Notable distinctions in ESMO-MCBS grades revealed seven trials with substantial clinical benefit (grades 5 to 4) and three with moderate to negligible benefit (grades 3 to 1). Bonus points, primarily based on the tail of the curve, were allocated to three trials for overall survival, one for progression-free survival, and one for a significant improvement in quality of life.
    CONCLUSIONS: Our evaluation of pembrolizumab across diverse cancers, especially in mNSCLC and HNSCC, revealed varied outcomes and challenges in clinical benefit interpretation. The assessment of clinical benefit, incorporating quantitative and qualitative endpoints, underscores the need to consider survivorship outcomes and patient perspectives for a comprehensive understanding.
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  • 文章类型: Journal Article
    背景:随着作为免疫检查点抑制剂的生物药物的发现,癌症的治疗得到了改善。2017年,FDA指定pembrolizumab,用于免疫疗法的免疫检查点抑制剂,作为第一个与组织无关的癌症治疗方法。
    目的:回顾pembrolizumab在肿瘤学中的应用,收集并检查有关pembrolizumab在癌症治疗中的有效性的最新发现。
    方法:从2015年1月至2023年12月,通过PubMed(Medline)使用“pembrolizumab”进行了文献综述,“癌症”和“治疗”作为搜索词。
    结果:Pembrolizumab证明了作为转移性非小细胞肺癌的主要治疗方法的有效性,无法切除的食道癌,头颈部鳞状细胞癌和显著三阴性乳腺癌的替代治疗,胆道,结直肠,子宫内膜,肾细胞,宫颈癌,和高度微卫星不稳定性或错配修复缺陷肿瘤。儿科应用包括治疗难治性霍奇金淋巴瘤。
    结论:对pembrolizumab的不断发展的研究可以使临床有更深入的了解,尽管挑战是可变的患者反应。Pembrolizumab已成为癌症治疗的重大突破,改善患者预后和安全性。
    BACKGROUND: Treatment of cancer has been improved with the discovery of biological drugs that act as immune checkpoint inhibitors. In 2017, FDA designated pembrolizumab, an immune checkpoint inhibitor employed in immunotherapy, as the first tissue-agnostic cancer treatment.
    OBJECTIVE: To review pembrolizumab\'s use in oncology, gather and examine the latest discoveries regarding the effectiveness of pembrolizumab in cancer treatment.
    METHODS: A literature review was conducted through PubMed(Medline) from January 2015 to December 2023 using \"pembrolizumab\", \"cancer\" and \"treatment\" as search terms.
    RESULTS: Pembrolizumab demonstrated effectiveness as primary treatment for metastatic nonsmall cell lung cancer, unresectable esophageal cancer, head and neck squamous cell carcinoma and alternative treatment for notable triple-negative breast cancer, biliary, colorectal, endometrial, renal cell, cervical carcinoma, and high microsatellite instability or mismatch repair deficiencies tumors. Pediatric applications include treatment for refractory Hodgkin lymphoma.
    CONCLUSIONS: Evolving research on pembrolizumab allows a deeper clinical understanding, despite challenges as variable patient responses. Pembrolizumab has emerged as a pivotal breakthrough in cancer treatment, improving patient outcomes and safety.
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  • 文章类型: Case Reports
    阴道癌是一种罕见的妇科恶性肿瘤。在局部疾病中,同步放化疗给予局部控制和更好的总体生存率,在转移性环境中,管理选择非常有限。此外,复发性宫颈,外阴,众所周知,阴道癌对治疗产生抗药性,因此,他们的预后仍然很差。
    我们在此介绍一个女性阴道癌淋巴结复发的病例,用三线免疫疗法有效治疗。我们还将提供有关晚期阴道癌的新治疗策略的文献综述,专注于pembrolizumab免疫疗法。
    Pembrolizumab可能是治疗阴道癌和外阴癌的一种有希望的选择,但是仍然缺乏支持其在此设置中使用的数据。该病例强调了对这种罕见疾病进行进一步调查和试验设计的必要性。
    UNASSIGNED: Vaginal cancer is a rare gynecologic malignancy. While in a localized disease, concurrent chemoradiation grants local control and better overall survival, in a metastatic setting, the management options are very limited. Furthermore, recurrent cervical, vulvar, and vaginal carcinomas notoriously develop resistance to treatment, and consequently, their prognosis is still poor.
    UNASSIGNED: We herein present the case of a woman with a nodal relapse of vaginal carcinoma, effectively treated with third-line immunotherapy. We will also provide a review of the literature on the new therapeutic strategies for advanced vaginal carcinoma, with a focus on pembrolizumab immunotherapy.
    UNASSIGNED: Pembrolizumab might represent a promising option for the management of vaginal and vulvar cancer, but data to support its use in this setting are still lacking. This case highlights the need for further investigation and trial designs for this rare disease.
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