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Takahiko Hashimoto



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    P88 - Targeted Therapy - Clinically Focused - ROS1 (ID 265)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P88.04 - Successful Low-Dose Treatment for Patients with ROS1-Rearranged NSCLC who Developed Crizotinib-Related Heart Failure. (ID 1770)

      00:00 - 00:00  |  Presenting Author(s): Takahiko Hashimoto

      • Abstract
      • Slides

      Introduction

      ROS1 rearrangements are identified in approximately 1% to 2% of non-small-cell lung cancers (NSCLCs). Crizotinib is an oral tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases. Crizotinib demonstrated marked antitumor activity for ROS1-rearranged NSCLC. Commonly reported crizotinib-related adverse events include visual disorder, nausea, diarrhea, and elevated transaminases. Due to the increasing experience with crizotinib, cardiotoxicity such as QT prolongation and bradycardia have been reported occasionally. However, little is known about the crizotinib-related heart failure, and its management has not been well established. We herein report the ROS1-rearranged NSCLC patient who developed heart failure due to crizotinib, but recovered by temporary drug withholding, and obtained a long-term response with reduced doses of crizotinib

      Methods

      Case Report

      Results

      An 80-year-old woman presented with persistent cough. CT of the chest revealed pulmonary mass and mediastinal lymphadenopathy. By transbronchial biopsy, she was diagnosed as having ROS1-rearranged adenocarcinoma of the lung. Her medical history included hypertension and hyperlipidemia, without any heart or coronary diseases. She started crizotinib 250 mg orally twice a day as her first-line treatment. On the day 8 of crizotinib therapy, she developed asymptomatic sinus bradycardia (heart rate, 47 bpm) and QT prolongation (QTc, 517 ms). After withholding of crizotinib for three days, heart rate recovered to 60 bpm and QTc recovered to 408 ms. Then she restarted crizotinib at a reduced dose of 200 mg twice a day. On the day 7 of reduced dose of crizotinib, she developed chest discomfort, leading to respiratory failure. Chest X-ray, chest CT, and echocardiography revealed cardiac enlargement, bilateral pleural effusion, and pulmonary congestion. She was diagnosed with heart failure due to crizotinib. Crizotinib was withheld again and furosemide 20 mg a day was administered. After seven days of this treatment, she recovered from heart failure. She resumed crizotinib treatment at a further reduced dose of 250 mg once a day. With this low-dose treatment, she had no subsequent recurrence of heart failure, bradycardia, or QT prolongation. The tumor shrank with this low-dose crizotinib. She has been on crizotinib at the same dose for 13 months with durable tumor response.

      Conclusion

      Cardiotoxicity is one of the notable adverse events related to crizotinib. In addition to bradycardia and QT prolongation, drug-induced heart failure can occur. This case report suggests that low dose crizotinib treatment could be tolerable for patients with crizotinib-related heart failure.

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