SPC365

Real-World Incidence and Risk Factors for Osimertinib-Associated Cardiotoxicity

Session: Sessão de Comunicações Orais 07 – Para além do evento agudo: preditores e desfechos após lesão miocárdica
Speaker: Beatriz Vargas Andrade

Congress: CPC 2026
Topic: P. Other
Theme: 30. Cardiovascular Disease in Special Populations
Subtheme: 30.6 Cardio-Oncology
Session Type: Comunicações Orais
FP Number: ---
Authors: Beatriz Vargas Andrade; João Cravo; Marta Vilela; Diogo Ferreira; Daniel Cazeiro; Andreia Magalhães; Miguel Menezes; Manuela Fiúza; Fausto J. Pinto
<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Introduction:&nbsp;</span></span></span></strong></span></span><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Osimertinib, a third-generation EGFR inhibitor, has improved survival in metastatic lung cancer, but its real-world cardiotoxicity and associated risk factors remain unclear.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Aim:&nbsp;</span></span></span></strong></span></span><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">To assess the real-world incidence, predictors, reversibility and clinical outcomes of osimertinib-related cardiotoxicity.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Methods:&nbsp;&nbsp;</span></span></span></strong></span></span><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">We conducted a retrospective single-center study including patients who started osimertinib from 2020 to 2024. Cardiotoxicity was defined as a &gt;10% reduction in LVEF, new-onset atrial fibrillation/flutter&nbsp;or any clinically relevant cardiovascular (CV) event. Predictors and outcomes were analyzed using multivariable logistic regression, Cox regression and Kaplan&ndash;Meier survival estimates.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Results:&nbsp;</span></span></span></strong><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">A total of 40 patients with lung adenocarcinoma were included (mean age 66&plusmn;3 years; 35% male). Most (88%) had metastatic disease and 50% received osimertinib as first-line therapy. Baseline mean LVEF was 56&plusmn;2%, with 2 patients (5%) showing LVEF &lt;50%. During a median follow-up of 31 (IQR 19-37) months, 6 patients (15%) developed cardiotoxicity: 3 (8%) had atrial fibrillation/flutter, 2 (5%) had LVEF decline, and 2 (5%) experienced other CV events. QT prolongation occurred in 6 patients (15%), without associated arrhythmias;&nbsp;4 patients (10%) required treatment discontinuation, with therapy resumed in 2.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Cardiotoxicity was significantly associated with baseline LVEF &lt;50% (p=0.019), older age (75&plusmn;4 vs. 65&plusmn;2 years, p=0.04) and higher baseline NT-proBNP [531 pg/mL (IQR 476&ndash;675) vs. 185 pg/mL (IQR 53&ndash;412), p=0.01]. Both patients with LVEF decline discontinued osimertinib and recovered and&nbsp;one resumed therapy. LVEF decline was linked to baseline LVEF &lt;50% (p=0.001) and not to treatment line or prior chemotherapy. New-onset atrial fibrillation/flutter was not associated with left atrial volume or obesity.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">CV hospitalization was associated with cardiotoxicity (50% vs. 9%, p=0.03) and&nbsp;lower hemoglobin (9.9&plusmn;0.5 vs. 11&plusmn;0.3 g/dL, p=0.02) and trended toward higher follow-up NT-proBNP [3769 pg/mL (IQR 989&ndash;7195) vs. 200 pg/mL (IQR 119&ndash;566), p=0.07]. In survival analysis, cardiotoxicity tended to increase the risk of CV hospitalization (HR 4.4; IC&nbsp;95% [1&ndash;22]; p=0.07). All-cause mortality was not associated with cardiotoxicity, LVEF decline or CV hospitalization, but was asssociated to lower follow-up hemoglobin (10&plusmn;0.4 vs. 12&plusmn;0.4 g/dL, p=0.01).</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Conclusions:&nbsp;</span></span></span></strong></span></span><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background-color:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Osimertinib-related cardiotoxicity occurred in 15% of patients and trended toward higher CV hospitalization, without affecting mortality, which was mainly driven by disease progression. Given its long-term use, vigilant monitoring is essential, especially in older patients, those with prior heart failure or elevated baseline NT-proBNP. </span></span></span></span></span></p>