Heart rate decrease during crizotinib treatment and potential correlation to clinical response

Authors

  • Sai-Hong Ignatius Ou MD, PhD,

    Corresponding author
    1. Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California
    • Corresponding author: Sai-Hong Ignatius Ou, MD, PhD, Health Science Associate Clinical Professor, Chao Family Comprehensive Cancer Center, Department of Medicine-Hematology/Oncology, University of California School of Medicine, 101 City Drive, Building 56, RT81, Room 241, Orange, CA 92868; Fax: (714) 456-2242; ignatius.ou@uci.edu

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  • Wilson P. Tong MD,

    1. Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California
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  • Michele Azada MPH,

    1. Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California
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  • Christina Siwak-Tapp PhD,

    1. Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California
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  • Joni Dy RN, OCN,

    1. Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California
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  • Jonathan A. Stiber MD

    1. Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
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Abstract

BACKGROUND

Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC). Sinus bradycardia (SB) is a side effect listed in its package insert. We investigated the frequency and timing of SB, patient characteristics associated with SB during crizotinib treatment, and potential correlation between heart rate (HR) changes and clinical response to crizotinib.

METHODS

A retrospective chart review was conducted of the timing and frequency of SB, patient characteristics, and clinical response of patients to crizotinib treatment.

RESULTS

Forty-twp patients who had ALK-rearranged or mesenchymal epithelial transition (MET)-amplified NSCLC and received treatment with oral crizotinib 250 mg twice daily who were enrolled in 2 crizotinib trials (PROFILE 1001 and PROFILE 1005) were analyzed. There was an average decrease of 26.1 beats per minute (bpm) from the pretreatment HR among all patients during crizotinib treatment. Twenty-nine patients (69%) experienced at least 1 episode of SB (HR, <60 bpm). The average time to the lowest HR recorded was 18.6 weeks (range, 5-72 weeks). Patients who experienced SB were significantly older (aged 55.8 years vs 47.8 years; P = .0336), had a lower pretreatment HR (mean, 77.9 bpm vs 100.6 bpm; P = .002), and were on crizotinib longer (52.9 weeks vs 24.6 weeks; P = .0050) than patients who did not experience SB. The overall response rate (P = .0195) and the maximum tumor shrinkage (P = .0205) were significantly greater in patients who experienced SB.

CONCLUSIONS

HR decrease is common during crizotinib treatment. It remains to be determined whether the correlation between HR decrease and clinical response to crizotinib reflects a biomarker of drug efficacy or a time/cumulative dose-dependent phenomenon. Cancer 2013;119:1969–1975. © 2013 American Cancer Society.

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