Uncommon Hepatobiliary Tumors

El-Khoueiry, Anthony B.

doi:10.1002/9781119196235.ch30

Cited by 5 publications

(4 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Forty percent of thyroidopathies were reported in a phase I study with nivolumab that involved 20 patients [59]. Besides this early trial, the rate of thyroid disorders for nivolumab was reported to be 0%-18.5% [46,55], similar to the rate with pembrolizumab. For both agents, hypothyroidism is the most prevalent toxicity, followed by hyperthyroidism and thyroiditis; severity is rarely higher than grade 2.Thyroid disorders are more frequent in women, which is consistent with the higher incidence observed in the general population.…”

Section: Thyroid Disordersmentioning

confidence: 75%

“…Two of these drugs, pembrolizumab and nivolumab, are approved in metastatic melanoma and lung cancer [38][39][40]. They are being tested in a variety of other solid tumors, including renal cell cancer, ovarian cancer, Hodgkin's lymphoma, esophageal carcinoma, colorectal cancer, hepatocarcinoma, and head and neck cancers [41][42][43][44][45][46][47]. Pidilizumab is an anti-PD1 that induces limited response in solid tumors; only hyperglycemia has been reported as an AE, with no information about autoimmunity [48][49][50].…”

Section: Programmed Death 1 Receptor and Ligand Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events

2016

View full text Add to dashboard Cite

In recent years, immune checkpoint inhibitors have emerged as effective therapies for advanced neoplasias. As new checkpoint target blockers become available and additional tumor locations tested, their use is expected to increase within a short time. Immune-related adverse events (irAEs) affecting the endocrine system are among the most frequent and complex toxicities. Some may be life-threatening if not recognized; hence, appropriate guidance for oncologists is needed. Despite their high incidence, endocrine irAEs have not been fully described for all immunotherapy agents available. This article is a narrative review of endocrinopathies associated with cytotoxic T lymphocyte-associated antigen-4, blockade of programmed death receptor 1 and its ligand inhibitors, and their combination. Thyroid dysfunction is the most frequent irAE reported, and hypophysitis is characteristic of ipilimumab. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for clinical management are suggested. Heterogeneous terminology and lack of appropriate resolution criteria in clinical trials make adequate evaluation of endocrine AEs difficult. It is necessary to standardize definitions to contrast incidences and characterize toxicity patterns. To provide optimal care, a multidisciplinary team that includes endocrinology specialists is recommended. The Oncologist 2016;21:804-816 Implications for Practice: Immune checkpoint inhibitors are already part of oncologists' therapeutic arsenal as effective therapies for otherwise untreatable neoplasias, such as metastatic melanoma or lung cancer.Their use is expected to increase exponentially in the near future as additional agents become available and their approval is extended to different tumor types. Adverse events affecting the endocrine system are among the most frequent and complex toxicities oncologists may face, and some may be lifethreatening if not recognized. This study reviews endocrinopathies associated to immune checkpoint inhibitors available to date. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for management are proposed.

show abstract

Section: Thyroid Disordersmentioning

confidence: 75%

Section: Programmed Death 1 Receptor and Ligand Inhibitorsmentioning

confidence: 99%

Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events

2016

View full text Add to dashboard Cite

show abstract

“…Early phase II data and case reports, however, suggest durable responses and a manageable safety profile in patients with controlled hepatitis B or C and hepatocellular carcinoma. [23,24] This cohort of patients is unlikely to be excluded from immunotherapy in the future.…”

Section: Overview Of Adverse Effectsmentioning

confidence: 99%

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer

et al. 2017

View full text Add to dashboard Cite

Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) represent a new treatment paradigm in non-small cell lung cancer. Three phase III trials have demonstrated a survival benefit and improved tolerability of nivolumab and pembrolizumab when compared with standard second-line chemotherapy.Nevertheless, the adverse events associated with PD-1 inhibitors are unique; early recognition and treatment are essential. This review summarizes the required monitoring and appropriate management of immune-related adverse events in lung cancer patients receiving these agents. The Oncologist 2017;22:70-80Implications for Practice: The potential adverse events of immune checkpoint inhibitors differ from conventional chemotherapy and can require a multidisciplinary approach. Continued education is important for all physicians to ensure optimal care for patients.

show abstract

“…As novel combinations and therapies are being considered for this disease, it is crucial that we better understand the biology associated with different HCC etiologies (i.e., hepatitis B and C, alcohol-related cirrhosis versus nonalcoholic steatohepatitis) because these could be associated with differential responses to molecularly or immunologically targeted therapies [18]. The recent success with immune checkpoint inhibitors in HCC is encouraging, but still, only 20% of the patients benefited [19]. With the evolving field of genomically and other biomarker-driven precision therapeutics, patients with HCC will benefit from rational combinations or, rather, select therapeutics to further improve outcomes.…”

Section: Trial Informationmentioning

confidence: 99%

Phase I Study of Lenalidomide and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

et al. 2016

View full text Add to dashboard Cite

Lessons Learned Combination therapies in patients with hepatocellular carcinoma can be associated with overlapping toxicity and are therefore poorly tolerated. Using sorafenib at the maximum tolerated dose can lead to a higher incidence of toxicities. Consequently, combination studies might evaluate sorafenib at alternative schedules or doses to improve tolerance, recognizing this could affect sorafenib efficacy. Although this combination was poorly tolerated, it does not exclude further evaluation of new-generation immunomodulator drugs or immune checkpoint inhibitors in the hope of optimizing tolerance and safety. Background. Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC), and to date, no combination therapy has demonstrated superior survival compared with sorafenib alone. The immunosuppressive microenvironment in HCC is a negative predictor for survival. Lenalidomide is an immunomodulator and antiangiogenic agent, with limited single-agent efficacy in HCC. Based on these data, we designed a phase I study of sorafenib plus lenalidomide to determine the safety and preliminary antitumor activity of this combination. Methods. This was an open-label, phase I study with a 3+3 dose escalation/de-escalation design. The starting dose of sorafenib was 400 mg p.o. b.i.d. and of lenalidomide was 15 mg p.o. daily with a planned dose escalation by 5 mg per cohort up to 25 mg daily. Dose de-escalation was planned to a sorafenib dose of 400 mg p.o. daily combined with two doses of lenalidomide: 10 mg p.o. daily for a 28-day cycle (cohort 1) and 10 mg p.o. daily for a 21- or 28-day cycle (cohort 2). Patients with cirrhosis, a Child-Pugh score of A-B7, and no previous systemic therapy were eligible. Results. Five patients were enrolled. Their median age was 56 years (range 39–61), and the ECOG status was 0–2. Four patients were treated at dose level (DL) 1. Because of the poor tolerance to the combination associated with grade 2 toxicities, one more patient was treated at DL −1. No dose-limiting toxicity was observed as specified per protocol. The most common toxicities were nausea, anorexia, pruritus, elevated liver enzymes, and elevated bilirubin. Three patients experienced one or more of the following grade 3 toxicities: fatigue (DL 1), increased bilirubin (DL 1), skin desquamation (DL −1), and elevated transaminase levels (DL 1). The median duration of therapy was 1 cycle (range 1–3). All patients discontinued the study, 4 because of progressive disease and 1 by patient preference. The best confirmed response was progressive disease. The median progression-free survival was 1.0 month (95% confidence interval 0.9–2.8), and the median overall survival was 5.9 months (95% confidence interval 3.68–23.4). Conclusion. In our small study, the combination of lenalidomide and sorafenib was poorly tolerated and showed...

show abstract

Uncommon Hepatobiliary Tumors

Cited by 5 publications

References 151 publications

Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events

Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer

Phase I Study of Lenalidomide and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Contact Info

Product

Resources

About