Advanced cancers may be accompanied by paraneoplastic disseminated intravascular coagulation (DIC), resulting in thromboembolism or thrombocytopenia. Thrombocytopenia can limit the feasibility of myelosuppressive chemotherapy. Therefore, an alternative treatment option is needed. This report described a patient with metastatic pulmonary adenocarcinoma with EGFR exon 20 insertion and paraneoplastic DIC. Frontline chemotherapy failed to control the disease and worsened thrombocytopenia. However, treatment with amivantamab resulted in a rapid resolution of DIC and produced a partial tumor response. Based on our experience, for patients with EGFR exon 20 insertions with paraneoplastic DIC, amivantamab could be considered a preferred frontline treatment.
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