Team-Based Approach to Management of Hypertension Associated with Angiogenesis Inhibitors

Patel, Shreya; Dushenkov, Anna; Jungsuwadee, Paiboon; Krishnaswami, Ashok; Barac, Ana

doi:10.1007/s12265-020-10024-5

Cited by 14 publications

(19 citation statements)

References 57 publications

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“…53 Hypertension must therefore be well controlled before starting therapy with atezolizumab plus bevacizumab; the most commonly used treatments are angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. 54 Other factors to consider Most patients are already receiving treatments that cause diarrhoea, which should be identified and treated. In patients with other cancers, GI AEs are more likely with regimens containing an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) agent and less likely with anti-PD-1 or -PD-L1 monotherapy.…”

Section: Proteinuria and Hypertensionmentioning

confidence: 99%

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Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

et al. 2021

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In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

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Section: Proteinuria and Hypertensionmentioning

confidence: 99%

Section: Factors To Consider Before Initiating First-line Atezolizumab Plus Bevacizumab Combination Therapymentioning

confidence: 99%

Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

et al. 2021

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“…There is no robust evidence for the choice of antihypertensive agents in patients who are receiving lenvatinib 24–27 . Angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and beta blockers can be used 27 .…”

Section: Management Of Lenvatinib‐associated Adverse Eventsmentioning

confidence: 99%

“…Angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and beta blockers can be used 27 . However, diuretics are not recommended as first‐line agents as they may worsen dehydration and electrolyte imbalance when diarrhea, a frequent adverse effect of lenvatinib, occurs 26 . An ACEI or ARB may be preferred if proteinuria is present 24,25 ; however, clear recommendations cannot be made, in view of earlier conflicting reports 28,29 .…”

Section: Management Of Lenvatinib‐associated Adverse Eventsmentioning

confidence: 99%

Expert consensus on the management of adverse events in patients receiving lenvatinib for hepatocellular carcinoma

Kim

Kang

et al. 2021

J of Gastro and Hepatol

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Lenvatinib is an oral multikinase inhibitor approved for use as first‐line treatment for patients with advanced hepatocellular carcinoma (HCC). However, like other agents in this drug class, lenvatinib is associated with clinically important adverse events (AEs) that could adversely affect patient outcomes. Hypertension, diarrhea, decreased appetite/weight, hand–foot skin reaction, and proteinuria are among the most common AEs associated with lenvatinib therapy. This article provides strategies for the effective management of lenvatinib‐associated AEs based on the expert opinion of authors and currently available literature. Due to the high risk of AEs in patients receiving lenvatinib, prophylactic measures and regular monitoring for AEs are recommended. Lenvatinib dose interruption, adjustment, or discontinuation of treatment may be required for patients who develop AEs. For grade 1 or 2 AEs, dose interruption is generally not required. For persistent or intolerable grade 2 or 3 AEs, lenvatinib treatment should be interrupted until symptoms improve/resolve to grade 0–1 or baseline levels. Thereafter, treatment should be resumed at the same or a lower dose. Disease progression may occur in patients who do not initially respond to treatment or receive a suboptimal lenvatinib dose following dose reduction, resulting in lack of efficacy. Therefore, to derive maximum treatment benefit and ensure long‐term disease control, lenvatinib should be maintained at the highest possible dose when managing AEs. To conclude, lenvatinib‐associated AEs can be managed with prophylactic measures, regular monitoring and symptomatic management, which can ensure continued treatment and maximum survival benefit in patients with advanced HCC receiving first‐line lenvatinib therapy.

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“…In addition, RAS blockade is beneficial for the proteinuric effect of VEGF inhibition and some studies have shown an association with improved overall survival in patients on RAS inhibitors. 44,47,48 CCBs are also effective, but for patients on TKIs, non-dihydropyridine CCB should be avoided as they inhibit the cytochrome p450 system that metabolizes TKIs and can therefore potentially worsen hypertension. 45 Beta blockers can be started second or third line if needed, or earlier if there is another indication for their use.…”

Section: Overview Of Hypertension With Anti-cancer Agentsmentioning

confidence: 99%

Onco-hypertension: Overview of hypertension with anti-cancer agents

Ruf

Yarandi

Ortiz-Melo

et al. 2021

Journal of Onco-Nephrology

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Onco-hypertension is an emerging field investigating the relationship between hypertension and cancer. This paper details one part of this relationship—the effect of anti-cancer agents on blood pressure. We review the evidence linking targeted therapies, immunotherapy, traditional chemotherapies, and hormonal agents with hypertension. Proposed pathophysiological mechanisms vary by drug but include endothelial dysfunction, altered sodium homeostasis, and nephrotoxicity. Despite growing interest in the field, there is a paucity of data on the clinical significance of treatment related hypertension and the optimal management strategy. This should be a focus of future studies.

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Team-Based Approach to Management of Hypertension Associated with Angiogenesis Inhibitors

Cited by 14 publications

References 57 publications

Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

Expert consensus on the management of adverse events in patients receiving lenvatinib for hepatocellular carcinoma

Onco-hypertension: Overview of hypertension with anti-cancer agents

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