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Cancer
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
Ablative treatments include hepatic arterial chemoembolization, selective internal radiation therapy, and radiofrequency ablation. All of these provide for palliation and cause tumor growth to become slower. They are done for patients awaiting liver transplantation. The radiofrequency ablation technique can be curative for tumors smaller than 2 cm. For tumors larger than 5 cm that are multifocal, have invaded the portal vein, or are metastatic, radiation therapy is usually ineffective. Sorafenib may slightly improve the patient’s condition. Newer agents can prolong survival for a longer time and/or cause fewer side effects. They include regorafenib, lenvatinib, and the immunotherapy agent called nivolumab. Levatinib is an alternative first-line therapy, providing progression-free survival that is better than with sorafenib.
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Nivolumab (Opdivo™) is a human IgG4 monoclonal antibody that blocks PD-1. It works as a checkpoint inhibitor, blocking a signal that inhibits the activation of T cells to attacking tumor cells. Nivolumab is used to treat a number of types of cancer, including lung, renal, head and neck, colon, and liver cancer, along with melanoma and Hodgkin’s lymphoma. It works by binding to the PD-1 receptor, thus preventing interaction with PD-L1/2 antigens on antigen-presenting cells (APCs) and other related cells in the tumor microenvironment. PD-1 is a negative regulator of T-cell activity thus, when inhibited by anti-PD-1 agents, potentiates T-cell proliferation and cytokine secretion.
Gastric Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Mark A. Baxter, Russell D. Petty
Another proposed biomarker for response to ICIs is MSI. Nivolumab has been licensed pan-cancer by the Food and Drug Administration (FDA) for MSI-high (MSI-H) tumors. In gastric cancer, response rates in deficient mismatch repair (dMMR) or MSI-H patients in the Phase I/II CheckMate-032 trial42 to combination ipilimumab and nivolumab were 50% compared with 19% in non-MSI-H.
Optimizing outcomes and managing adverse events in locally advanced or metastatic urothelial cancer: a clinical pharmacology perspective
Published in Expert Review of Clinical Pharmacology, 2023
Pratap Singh, Anand Rotte, Anthony A. Golsorkhi, Sandhya Girish
Nivolumab has been evaluated as adjuvant treatment following radical surgery for advanced UC patients with high risk of recurrence and as second-line treatment in mUC patients progressing after chemotherapy. In the MIBC patients with high risk of recurrence, multicenter, open-label, randomized phase 3 study showed that nivolumab treatment (monotherapy) significantly improved the disease-free survival compared to placebo with HR for disease recurrence or death of 0.70 (p < 0.001) in all patients and 0.55 (p < 0.001) in patients with PD-L1 expression level of 1% or more [68]. In mUC patients progressing after platinum containing therapy, multicenter phase 2 study showed that nivolumab treatment had a confirmed objective response in all patients, patients with PD-L1 expression of 5% or more, 1% or more and < 1% was 20% (n = 52/265), 28% (n = 23/81), 24% (n = 29/122) and 16% (n = 23/143) respectively. Median OS in all patients, patients with PD-L1 expression of 1% or more and < 1% was 8.74 months, 11.30 months and 5.95 months respectively [69]. Commonly adverse events seen in 20% or more patients receiving nivolumab monotherapy include, fatigue, rash, pruritus, musculoskeletal pain, asthenia, diarrhea, nausea, vomiting, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, pyrexia, headache, back pain, abdominal pain, upper respiratory tract infection, and urinary tract infection [summarized from package insert for nivolumab].
Current status and novel insights into the role of metastasectomy in the era of immunotherapy
Published in Expert Review of Anticancer Therapy, 2023
Efstathia Liatsou, Diamantis I. Tsilimigras, Panagiotis Malandrakis, Maria Gavriatopoulou, Ioannis Ntanasis-Stathopoulos
Trials have also been designed with some of them showing substantial evidence encouraging the use of neoadjuvant immunotherapy (Table 1). The phase 1 of a randomized controlled trial conducted at the University of Pittsburg evaluated the safety and potential effectiveness of the combination of ipilimumab with interferon-α2b in 30 patients with advanced melanoma, as well as biomarkers obtained from tumor biopsy that could play a prognostic role for relapse [31]. After a follow-up of 32 months the pathologic complete response rate was 32% (95% CI, 18–51%), whereas biomarker analysis showed that an increased tumor T-cell clonality in the primary tumor following neoadjuvant therapy was associated with improved relapse free survival [31]. A phase II 3-arm trial investigating the use of nivolumab with or without ipilimumab or relatlimab (LAG-3 blocking antibody) before surgery for patients with stage IIIB-IV melanomas at the M.D. Anderson Cancer Center is currently ongoing (NCT02519322). Patients are going to be randomized to receive either nivolumab alone either nivolumab with ipilimumab or nivolumab with relatlimab followed by surgery on day 57. After surgery, patients will receive nivolumab intravenously every 2 weeks for a total of 13 doses (NCT02519322).
Pregnancy outcome after early exposure to nivolumab, a PD-1 checkpoint inhibitor for relapsed Hodgkin’s lymphoma
Published in Clinical Toxicology, 2022
Janine R. Hutson, Genevieve Eastabrook, Facundo Garcia-Bournissen
The PD-1 pathway is likely involved in maternal immune tolerance to the fetus, which suggests that blocking this pathway in pregnancy could lead to maternal immune activation against the placenta or the fetus, or altered immune responses in the neonate [1,2]. The risk of an immune-mediated response to the fetus during blockage of the PD-1 axis could be patient-specific if fetal allogenicity is driven by paternal antigenic components. In monkeys, nivolumab at levels >9 times higher than therapeutic levels led to increased spontaneous abortions and neonatal death, but surviving infants had no apparent malformations nor effects on neurobehavioural, immunological, or clinical pathology parameters up to 6 months of age [2]. Current experience in human pregnancy is limited to five case reports resulting in seven liveborn infants [3–5]. Of these, two patients had an early exposure similar to our patient, after which nivolumab was discontinued. One case report suggested congenital hypothyroidism which may be an immune-related adverse event from maternal anti-PD1 exposure [3]. Our case adds to the favorable pregnancy outcome literature with early exposure to nivolumab, specifically in patients who become pregnant prior to the recommended 5 months after the last dose.