Seminars in oncology最新文献

{"title":"Real-world experience with CDK4-6 inhibition in the old and oldest old with a diagnosis of breast cancer","authors":"","doi":"10.1053/j.seminoncol.2024.01.003","DOIUrl":"10.1053/j.seminoncol.2024.01.003","url":null,"abstract":"<div><p><span><span><span>This study describes characteristics, toxicity and survival in old patients with HR+/HER2-breast cancer (BC) treated with CDK4/6 inhibitors. Retrospective observational study that included patients ≥ 75 years with HR+/HER2-BC treated with CDK4/6 inhibitors between 2017 and 2021. Patients’ general and cancer-related data were collected. Comprehensive Geriatric Assessment scales were gathered. </span>Adverse events<span><span> reported before each cycle were included. At the end of the follow-up period, mortality was retrospectively registered from medical records. All 19 patients (94.7% women, median age 77.9 ± 10.1) were at risk of </span>frailty (G8 ≤ 14) and malnutrition (MNA-SF ≤ 11). Most were independent (52.7% Lawton ≥ 6), had no </span></span>cognitive impairment<span><span> (89.5%, MMSE ≥ 24), poor physical performance (70%, SPPB &lt; 8; 62.5% TUG ≥ 12’’) and polypharmacy (72.2%). Almost half had stage IV disease (47.1%). Palbociclib+letrozole was the most frequently prescribed treatment (36.8%). All patients developed some toxicity (94.7% hematologic, 36.8% renal) but except one, grade ≤ 2. Over the 42-month follow-up period, 10 reported progression and 8 died. The </span>median survival time was 19.9 ± 3.4 months. Five months after starting treatment, the probability of survival was 73%. At 30 months, 53% of patients survived. We found a high risk of frailty and </span></span>drug toxicity in this small sample. Most patients presented hematologic toxicity but to a low degree. The probability of survival increases with treatment.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 3","pages":"Pages 95-105"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139949520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR T-cell therapy: A collaboration between authorized treatment centers and community oncologists","authors":"","doi":"10.1053/j.seminoncol.2024.02.001","DOIUrl":"10.1053/j.seminoncol.2024.02.001","url":null,"abstract":"<div><p>With the approval of the first CAR T-cell products for hematological malignancies in 2017, these autologous cell therapies have changed the treatment paradigm for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL), who have a poor prognosis and few effective treatment options. Despite the demonstrated clinical benefit in patients with r/r diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, many patients who are eligible for CAR T-cell therapies do not receive them or are treated with CAR T cells as a later line of therapy at advanced stages of disease. Several barriers exist for referring patients to an authorized treatment center (ATC) for CAR T-cell therapy. Although most patients with NHL are treated by community-based oncologists, educational gaps may exist for some community oncologists about the availability of CAR T-cell therapies in certain indications, the overall treatment process, and how they can access these therapies for their patients. In addition to navigation of the referral process from the community setting to the ATC, other barriers include timely identification of candidates eligible for CAR T-cell therapy and logistical and reimbursement concerns. Here, we examine the patient CAR T-cell experience, which begins and ends in the community setting, and identify and discuss opportunities for improved collaboration between community oncologists and ATC physicians to help address barriers to treatment and enhance patient outcomes. Treatment decisions for a patient's second or third line of therapy for NHL are critically important, owing to declining probabilities for favorable outcomes with each successive line of therapy. For patients who are eligible, CAR T-cell therapies should be considered as early as possible in their treatment course. A better understanding of the CAR T-cell process, the patient's experience, and the collaboration necessary for timely patient identification, better access, and successful outcomes will enable more patients to benefit from CAR T-cell therapies.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 3","pages":"Pages 87-94"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775424000046/pdfft?md5=37592ae048944580f3ea166540526d16&pid=1-s2.0-S0093775424000046-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139949522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP inhibitors in ovarian cancer","authors":"Ian S. Goldlust,&nbsp;Elena Guidice,&nbsp;Jung-min Lee","doi":"10.1053/j.seminoncol.2024.01.001","DOIUrl":"10.1053/j.seminoncol.2024.01.001","url":null,"abstract":"<div><p><span><span>Poly-ADP-ribose polymerase inhibitors (PARPis) were first approved for the treatment of </span>epithelial ovarian cancer (EOC), where as a maintenance therapy they transformed clinical management of this disease in both patients with and without </span>homologous recombination<span><span> deficiency. In this review, we provide a historical overview of PARPi use in EOC and discuss recent updates on overall survival data, highlighting their impact on regulatory approvals. We explore their potential as combination regimens with </span>antiangiogenic<span> and cell-cycle checkpoint inhibitors, as well as other small molecule inhibitors, to overcome resistance mechanisms and enhance therapeutic efficacy, providing a future perspective on the use of PARPis in EOC treatment.</span></span></p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 1","pages":"Pages 45-57"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139459981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP1 roles in DNA repair and DNA replication: The basi(c)s of PARP inhibitor efficacy and resistance","authors":"Petar-Bogomil Kanev,&nbsp;Aleksandar Atemin,&nbsp;Stoyno Stoynov,&nbsp;Radoslav Aleksandrov","doi":"10.1053/j.seminoncol.2023.08.001","DOIUrl":"10.1053/j.seminoncol.2023.08.001","url":null,"abstract":"<div><p>Genome integrity is under constant insult from endogenous and exogenous sources. In order to cope, eukaryotic cells have evolved an elaborate network of DNA repair that can deal with diverse lesion types and exhibits considerable functional redundancy. PARP1 is a major sensor of DNA breaks with established and putative roles in a number of pathways within the DNA repair network, including repair of single- and double-strand breaks as well as protection of the DNA replication fork. Importantly, PARP1 is the major target of small-molecule PARP inhibitors (PARPi), which are employed in the treatment of homologous recombination (HR)-deficient tumors, as the latter are particularly susceptible to the accumulation of DNA damage due to an inability to efficiently repair highly toxic double-strand DNA breaks. The clinical success of PARPi has fostered extensive research into PARP biology, which has shed light on the involvement of PARP1 in various genomic transactions. A major goal within the field has been to understand the relationship between catalytic inhibition and PARP1 trapping. The specific consequences of inhibition and trapping on genomic stability as a basis for the cytotoxicity of PARP inhibitors remain a matter of debate. Finally, PARP inhibition is increasingly recognized for its capacity to elicit/modulate anti-tumor immunity. The clinical potential of PARP inhibition is, however, hindered by the development of resistance. Hence, extensive efforts are invested in identifying factors that promote resistance or sensitize cells to PARPi. The current review provides a summary of advances in our understanding of PARP1 biology, the mechanistic nature, and molecular consequences of PARP inhibition, as well as the mechanisms that give rise to PARPi resistance.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 1","pages":"Pages 2-18"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775423000611/pdfft?md5=84ff3c62330ada1df60673d49569a10e&pid=1-s2.0-S0093775423000611-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10317051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP inhibitors for prostate cancer","authors":"Ossian Longoria ,&nbsp;Nick Beije ,&nbsp;Johann S. de Bono","doi":"10.1053/j.seminoncol.2023.09.003","DOIUrl":"10.1053/j.seminoncol.2023.09.003","url":null,"abstract":"<div><p>Poly(ADP-ribose) polymerase (PARP) inhibitors have transformed the treatment landscape for patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in DNA damage response genes. This has also led to widespread use of genomic testing in all patients with mCRPC. The current review will give an overview of (1) the current understanding of the interplay between DNA damage response and PARP enzymes; (2) the clinical landscape of PARP inhibitors, including the combination of PARP inhibitors with other agents such as androgen-receptor signaling agents; (3) biomarkers related to PARP inhibitor response and resistance; and (4) considerations for interpreting genomic testing results and treating patients with PARP inhibitors.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 1","pages":"Pages 25-35"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775423000623/pdfft?md5=caa912a465a6612b4b257fdb3415d978&pid=1-s2.0-S0093775423000623-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41177047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seminars in oncology 50th anniversary","authors":"Tito Fojo","doi":"10.1053/j.seminoncol.2024.02.003","DOIUrl":"10.1053/j.seminoncol.2024.02.003","url":null,"abstract":"","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 1","pages":"Page 1"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP inhibitors: A review of the pharmacology, pharmacokinetics, and pharmacogenetics","authors":"Yi Zeng ,&nbsp;Oluwatobi Arisa ,&nbsp;Cody J. Peer ,&nbsp;Antonio Fojo ,&nbsp;William D. Figg","doi":"10.1053/j.seminoncol.2023.09.005","DOIUrl":"10.1053/j.seminoncol.2023.09.005","url":null,"abstract":"<div><p>PARP<span><span><span><span><span> inhibitors have emerged as a promising class of anticancer<span> agents approved for the treatment of ovarian, breast, prostate, and </span></span>pancreatic cancer<span><span>. These inhibitors target PARP </span>enzymes<span> involved in DNA repair pathways and exhibit remarkable efficacy in cancers with </span></span></span>genetic<span> deficiencies in the homologous recombination<span> pathway responsible for mending DNA double-strand breaks. While all </span></span></span>PARP inhibitors<span> demonstrate potent and selective inhibition of PARP1 and </span></span>PARP2, the key enzymes involved in DNA repair, each agent within the class possesses unique pharmacological profiles distinguishing them from one another.</span></p><p><span><span>This review aims to comprehensively examine the properties of the entire PARP inhibitor class while emphasizing individual pharmacologic and pharmacokinetic distinctions that inform clinical recommendations. Currently, four agents, namely </span>olaparib, </span>rucaparib<span>, niraparib<span>, and talazoparib<span>, have obtained approval in the United States and Europe. Olaparib, the first approved PARP inhibitor, has been extensively studied and is indicated for a wider range of cancer types.</span></span></span></p><p>Niraparib and talazoparib, the more recent additions to the PARP inhibitor class, possess the longest half-lives and are formulated for convenient once-daily dosing, alleviating the pill burden for patients when compared to older agents. Moreover, talazoparib undergoes minimal hepatic metabolism, reducing the potential for drug-drug interactions. Notably, niraparib is the sole PARP inhibitor recommended for dose reduction in hepatically impaired populations, whereas talazoparib and olaparib should be dose reduced in renally impaired populations. The mechanisms underlying these dose adjustment recommendations are further explored in this review.</p><p>Additionally, this review briefly covers veliparib<span>, a PARP inhibitor under development, and two recently approved PARP inhibitors in China, fuzuloparib and pamiparib<span>. Although significant progress has been made in understanding PARP inhibitors, there are several unanswered questions that remain, necessitating further research across a broader spectrum of cancer types within this evolving class of anticancer agents.</span></span></p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 1","pages":"Pages 19-24"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond BRCA: Diagnosis and management of homologous recombination repair deficient pancreatic cancer","authors":"Meredith LaRose,&nbsp;Gulam A. Manji,&nbsp;Susan E. Bates","doi":"10.1053/j.seminoncol.2023.11.001","DOIUrl":"10.1053/j.seminoncol.2023.11.001","url":null,"abstract":"<div><p><span><span><span>Approximately 4%–7% of patients diagnosed with pancreatic adenocarcinoma (PDAC) are found to harbor deleterious </span>germline mutations in </span>BRCA1<span> and/or BRCA2<span>. Loss of function of BRCA1<span> and/or BRCA2 results in deficiency in homologous </span></span></span></span>recombination repair<span><span><span> (HRR), a critical DNA repair<span> pathway, and confers sensitivity to certain DNA damaging agents, including platinum chemotherapy and </span></span>PARP inhibitors<span>. The PARP inhibitor </span></span>olaparib<span><span><span> is food and drug administration (FDA) approved for use in pancreatic cancer based on the POLO trial, which found that maintenance olaparib significantly prolonged </span>progression free survival<span> compared to placebo among patients with germline BRCA1 or BRCA2 mutations and metastatic PDAC that had not progressed following frontline platinum-based chemotherapy. Recently, there has been considerable interest in identifying patients without BRCA inactivation whose tumors also exhibit properties of HRR deficiency and thus may be susceptible to therapies with proven benefit in cancers harboring </span></span>BRCA mutations. Here, we discuss methods for identification of HRR-deficiency and review the management of HRR-deficient cancers with a focus on HRR-deficient PDAC.</span></span></p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"51 1","pages":"Pages 36-44"},"PeriodicalIF":4.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138520725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary adrenal insufficiency induced by immune checkpoint inhibitors: biological, clinical, and radiological aspects","authors":"Serafina Martella ,&nbsp;Minke Lucas ,&nbsp;Michele Porcu ,&nbsp;Laura Perra ,&nbsp;Nerina Denaro ,&nbsp;Andrea Pretta ,&nbsp;Giulia Deias ,&nbsp;Karen Willard-Gallo ,&nbsp;Hector Soto Parra ,&nbsp;Luca Saba ,&nbsp;Mario Scartozzi ,&nbsp;Demi Wekking ,&nbsp;Marleen Kok ,&nbsp;Marco Maria Aiello ,&nbsp;Cinzia Solinas","doi":"10.1053/j.seminoncol.2023.11.003","DOIUrl":"10.1053/j.seminoncol.2023.11.003","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICI) have become a cornerstone in medical oncology, with evolving therapeutic strategies and applications. These monoclonal antibodies, designed to enhance immune responses, have revealed a spectrum of immune-related adverse events (irAEs). While many irAEs exhibit favorable responses to corticosteroid or immunosuppressive therapy, most ICI-related endocrinopathies necessitate lifelong replacement therapy and pose significant clinical challenges. Adrenal insufficiency (AI), a noteworthy endocrine irAE, can manifest as primary AI (PAI) or secondary AI (SAI), resulting from adrenal or pituitary gland dysfunction, respectively. ICI-induced AI, albeit relatively infrequent, occurs in 1-2% of patients receiving single-agent anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) or Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) therapies and in a higher range of 4-9% when ICIs are used in combinations. Recognizing and addressing ICI-induced PAI is crucial, as it often presents with acute and potentially life-threatening symptoms, especially considering the expanding use of ICI therapy. This review provides an updated overview of ICI-induced PAI, exploring its clinical, diagnostic, and radiological aspects.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 6","pages":"Pages 144-148"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138546818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDK4/6 inhibitors in the treatment of metastatic breast cancer: Focus on toxicity and safety","authors":"Demi Wekking ,&nbsp;Matteo Lambertini ,&nbsp;Mariele Dessì ,&nbsp;Nerina Denaro ,&nbsp;Fabio Bardanzellu ,&nbsp;Ornella Garrone ,&nbsp;Mario Scartozzi ,&nbsp;Cinzia Solinas","doi":"10.1053/j.seminoncol.2024.01.002","DOIUrl":"10.1053/j.seminoncol.2024.01.002","url":null,"abstract":"<div><div>The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). When combined with an aromatase inhibitor or fulvestrant, these agents have been approved as first-line therapy in the metastatic setting. Abemaciclib has also gained FDA approval for patients with HR-positive, HER2-negative, node-positive, early BC at high risk of recurrence. Moreover, ribociclib has recently improved disease-free survival in patients with stage II or III HR+/HER2-negative early BC. CDK4/6 inhibitors have favorable safety profiles. However, the available agents have different toxicity profiles that must be clearly discussed with the patients for optimal clinical decisions. This manuscript aims to review CDK4/6 inhibitor-related treatment-associated adverse events, identify risk factors for intolerable adverse events, and assess their safety in special patient populations such as the elderly and those with renal insufficiency. Enhanced knowledge and understanding of CDK4/6 inhibitor-related toxicities can improve treatment strategies and ultimately enhance patient care.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 6","pages":"Pages 131-139"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139460063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}