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Efficacy of Pyrotinib in a Heavily Pretreated Patient with Lung Adenocarcinoma Harboring HER2 Amplification and Exon 20 Insertions: A Case Report

ABSTRACT: Abstract The clinical benefits of HER2 inhibitors in patients with non-small cell lung cancer (NSCLC) have been limited. There is a paucity of effective therapies in NSCLC after developing resistance to initial anti-HER2 therapy. Herein, we presented the clinical benefit of pyrotinib in a 53-year-old patient with advanced lung adenocarcinoma whose circulating tumor DNA (ctDNA) analysis of pleural effusion revealed the coexistence of HER2 exon 20 p.Y772_A775dup (mutation ratio: 38.86%) and HER2 amplification (copy number: 4.5) following failures of multiple therapies including afatinib and ado-trastuzumab emtansine (T-DM1). Notably, pyrotinib treatment induced rapid and marked improvement of clinical symptoms, and partial response was observed after 8 weeks. CtDNA monitoring during the treatment showed that the mutation ratio of HER2 decreased to 7.99%, and the amplification disappeared. The patient achieved a progression-free survival of 7.5 months after treatment with pyrotinib. Thus, pyrotinib may be a new treatment strategy for the subgroup of lung adenocarcinoma patients, with coexistence of HER2 exon 20 p.Y772_A775dup and HER2 amplification even after failures of multiple anti-HER2 therapies. It also indicated the value of capture-based next-generation sequencing to monitor and guide therapy.

SUBMITTER: Shan J

PROVIDER: S-EPMC7537839 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundStandard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy.MethodsThis is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate.DiscussionThe addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds.Trial registrationClinicalTrials.gov Identifier: NCT04382300 . Registered on May 11, 2020.

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Efficacy of Pyrotinib in a Heavily Pretreated Patient with Lung Adenocarcinoma Harboring HER2 Amplification and Exon 20 Insertions: A Case Report

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