Takotsubo Syndrome in a Patient with Metastatic Renal Cell Carcinoma Treated with Pembrolizumab Plus Axitinib

Abstract

We report the case of a patient with metastatic renal cell carcinoma who developed Takotsubo syndrome (TTS) 6 days after starting pembrolizumab plus axitinib as first-line treatment. Coronary angiogram was negative for obstructive coronary artery disease and echocardiogram revealed a depressed left ventricular ejection fraction with apical akinesis. Axitinib was discontinued and myocardial contractile function fully recovered 23 days after the initial presentation. The treatment was safely resumed and granted a partial response of disease. A literature review regarding TTS in patients receiving VEGFR tyrosine kinase inhibitors and/or immune checkpoint inhibitors was performed. TTS is reported as a rare adverse event and the possible causal relationship between TTS and antineoplastic therapy is still unclear. Further research is warranted to better understand cardiotoxicity mechanisms and their management.

Takotsubo Cardiomyopathy in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Summary of Included Cases

“…Regarding time of TTS presentation, there are lines of evidence in our review (median time on immunotherapy at the time of TTS presentation was found to be 77 days) and in other studies [11,29] denoting that immune-related TTS represents a rather delayed form of cardiotoxicity. However, we believe that these observations may be biased from the small sample size.…”

“…Other possible stressors included the presence of non-cardiac irAEs [15,[17][18][19]23,26,28,29], infections [21], and infusion reactions [16]. Other risk factors, such as active smoking and cardiovascular comorbidities, have been previously described [14] and were also identified in our study [17][18][19].…”

“…In addition, several anticancer drugs (e.g., trastuzumab, anthracyclines, axitinib, 5-FU, etc. ), of which the association with TTS has been previously described [11,32], may also be also implicated in triggering TTS in some of the cases [20,25,26,29]. The abundance of potential stressors suggests that TTS may not be a direct outcome of immune-related toxicity, and that therapy-induced immune stimulation may aggravate other underlying mechanisms.…”

“…However, we believe that these observations may be biased from the small sample size. This is highlighted in cases where TTS occurred after hours or several days [15][16][17][18]24,27,29] from the last ICI administration.…”

“…Of the seventy-seven articles initially retrieved through the literature search, fifteen met all eligibility criteria and were included in the systematic review [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. One additional unpublished case from the Third Department of Internal Medicine, Sotiria General Hospital for Chest Diseases, National and Kapodistrian University of Athens, Athens, Greece, was also included.…”