TY - JOUR
T1 - Case Report
T2 - Exceptional Response to Poziotinib in Patient with Metastatic Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutation
AU - Prelaj, Arsela
AU - Bottiglieri, Achille
AU - Bhat, Gajanan
AU - Washington, Rocky
AU - Calareso, Giuseppina
AU - Greco, Gabriella Francesca
AU - Ferrara, Roberto
AU - Brambilla, Marta
AU - De Toma, Alessandro
AU - Occhipinti, Mario
AU - Manglaviti, Sara
AU - Soro, Alberto
AU - Ganzinelli, Monica
AU - Lo Russo, Giuseppe
AU - Proto, Claudia
N1 - Funding Information:
Sarah K. Madsen, PhD (Spectrum Pharmaceuticals, Inc.) provided medical writing support.
Publisher Copyright:
Copyright © 2022 Prelaj, Bottiglieri, Bhat, Washington, Calareso, Greco, Ferrara, Brambilla, De Toma, Occhipinti, Manglaviti, Soro, Ganzinelli, Lo Russo and Proto.
PY - 2022/6/8
Y1 - 2022/6/8
N2 - Among the several next-generation tyrosine kinase inhibitors (TKIs) tested against uncommon EFGR alterations, poziotinib has been demonstrated to be a powerful agent for metastatic non-small-cell lung cancer (mNSCLC) with aberrations in HER2 exon 20, and FDA approval is being sought in the previously-treated population. Poziotinib has also shown activity in mNSCLC with aberrations in EGFR exon 20. Herein, we report the first published case of a patient affected by mNSCLC harbouring an EGFR exon 20 insertion (EGFRex20ins) mutation who achieved a complete response (CR) under treatment with poziotinib as part of the ZENITH20 trial. In January 2021, a former smoker 62-year-old female patient was diagnosed with relapse, after two surgeries and post-operative chemotherapy of mNSCLC, at liver and retroperitoneal nodes. Given the identification by Next Generation Sequencing (NGS) of EGFRex20ins mutation, she was enrolled in ZENITH20-cohort 5 trial, a phase 2 multicentre study aimed to assess the efficacy and safety of poziotinib in patients with EGFR or HER2 exon 20 insertion mutations. Poziotinib as first-line systemic therapy for metastatic disease was initiated at the end of January 2021 and administrated at the initial dosage of 8 mg orally twice daily (BID). The most common side effects from the beginning of the treatment included alopecia, macular skin rash, diarrhoea, xerostomia, and conjunctivitis. Due to these adverse events, poziotinib was discontinued during the first 3 months and then reduced to 6 mg orally BID in April 2021. After the dose de-escalation, the adverse events ameliorated, and the patient better tolerated the treatment without further interruption. Since the first reevaluation (after 4 weeks of therapy), the treatment with poziotinib resulted to be remarkably effective, with a partial response (PR) subsequently confirmed in May and July 2021. Then, in October 2021, a CT scan confirmed a CR, maintained with good tolerance at the last reevaluation in February 2022. Treatment is still ongoing at the same dosage. In this case, poziotinib has represented a successful and well-tolerated first-line treatment alternative to chemotherapy in this patient with EGFR exon 20 insertion mutated mNSCLC.
AB - Among the several next-generation tyrosine kinase inhibitors (TKIs) tested against uncommon EFGR alterations, poziotinib has been demonstrated to be a powerful agent for metastatic non-small-cell lung cancer (mNSCLC) with aberrations in HER2 exon 20, and FDA approval is being sought in the previously-treated population. Poziotinib has also shown activity in mNSCLC with aberrations in EGFR exon 20. Herein, we report the first published case of a patient affected by mNSCLC harbouring an EGFR exon 20 insertion (EGFRex20ins) mutation who achieved a complete response (CR) under treatment with poziotinib as part of the ZENITH20 trial. In January 2021, a former smoker 62-year-old female patient was diagnosed with relapse, after two surgeries and post-operative chemotherapy of mNSCLC, at liver and retroperitoneal nodes. Given the identification by Next Generation Sequencing (NGS) of EGFRex20ins mutation, she was enrolled in ZENITH20-cohort 5 trial, a phase 2 multicentre study aimed to assess the efficacy and safety of poziotinib in patients with EGFR or HER2 exon 20 insertion mutations. Poziotinib as first-line systemic therapy for metastatic disease was initiated at the end of January 2021 and administrated at the initial dosage of 8 mg orally twice daily (BID). The most common side effects from the beginning of the treatment included alopecia, macular skin rash, diarrhoea, xerostomia, and conjunctivitis. Due to these adverse events, poziotinib was discontinued during the first 3 months and then reduced to 6 mg orally BID in April 2021. After the dose de-escalation, the adverse events ameliorated, and the patient better tolerated the treatment without further interruption. Since the first reevaluation (after 4 weeks of therapy), the treatment with poziotinib resulted to be remarkably effective, with a partial response (PR) subsequently confirmed in May and July 2021. Then, in October 2021, a CT scan confirmed a CR, maintained with good tolerance at the last reevaluation in February 2022. Treatment is still ongoing at the same dosage. In this case, poziotinib has represented a successful and well-tolerated first-line treatment alternative to chemotherapy in this patient with EGFR exon 20 insertion mutated mNSCLC.
KW - complete response (CR)
KW - EGFR
KW - exon 20 insertion (ex20ins)
KW - exon 20 insertion mutation
KW - lung cancer
KW - NSCLC
KW - poziotinib
KW - target therapy
UR - http://www.scopus.com/inward/record.url?scp=85133367545&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85133367545&partnerID=8YFLogxK
U2 - 10.3389/fonc.2022.902967
DO - 10.3389/fonc.2022.902967
M3 - Article
AN - SCOPUS:85133367545
SN - 2234-943X
VL - 12
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 902967
ER -