Poziotinib for EGFR and HER2 exon 20 insertion mutation in advanced NSCLC: Results from the expanded access program

The treatment of metastatic non–small-cell lung cancer (mNSCLC) patients with EGFR/HER2 exon 20 insertion mutation (i-mut) remains an unmet clinical need. Poziotinib, a new generation tyrosine kinase inhibitor, is currently under investigation as a potential targeted therapy. This compassionate stud...

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Published in:European journal of cancer (1990) 2021-05, Vol.149, p.235-248
Main Authors: Prelaj, Arsela, Bottiglieri, Achille, Proto, Claudia, Lo Russo, Giuseppe, Signorelli, Diego, Ferrara, Roberto, Galli, Giulia, De Toma, Alessandro, Viscardi, Giuseppe, Brambilla, Marta, Lobefaro, Riccardo, Nichetti, Federico, Manglaviti, Sara, Occhipinti, Mario, Labianca, Alice, Ganzinelli, Monica, Gallucci, Rosaria, Zilembo, Nicoletta, Greco, Gabriella Francesca, Torri, Valter, de Braud, Filippo, Garassino, Marina C.
Format: Article
Language:English
Subjects:
Diarrhea
Disease control
Dosage
EGFR
Enzyme inhibitors
Epidermal growth factor receptors
ErbB-2 protein
Exon 20 insertion mutation
Fatalities
HER2
Insertion
Kinases
Lung cancer
Metastases
Mucositis
Mutation
Non-small cell lung carcinoma
NSCLC
Oral administration
Patients
Pneumonitis
Poziotinib
Protein-tyrosine kinase
Small cell lung carcinoma
Survival
Toxicity
Tyrosine
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Summary:The treatment of metastatic non–small-cell lung cancer (mNSCLC) patients with EGFR/HER2 exon 20 insertion mutation (i-mut) remains an unmet clinical need. Poziotinib, a new generation tyrosine kinase inhibitor, is currently under investigation as a potential targeted therapy. This compassionate study of its use aims to describe the activity/toxicity of poziotinib in mNSCLC with EGFR/HER2-exon-20-i-mut. NSCLC patients who were treated either with EGFR or HER2 exon 20-i-mut within an expanded access program were included in this study. Poziotinib (16 mg or less) was administrated orally quaque die (QD). The primary end-point was the overall response rate (ORR) assessed by central review using RECIST v1.1, and secondary end-points were median progression free survival (PFS), disease control rate (DCR), median overall survival (OS) and toxicity. The median age of all the 30 patients was 58 years (25–80 years), most of them were females (73%); ECOG 0–1 (83%), EGFR i-mut (73%) and pre-treated (83%). 73% started with poziotinib at a dose of 16 mg. At data cut-off, 22 of 33 patients (73%) experienced a progress in the disease and 12 of 30 (40%) died. Median PFS was 5.6 months (95% CI: 3.6–6.7 months) and the mOS 9.5 months (95% CI: 5.3 – not-reached months). The ORR was 30% (EGFR/HER2: 23/50%) and DCR 80%. G3 AEs were reported in 66% of the patients and were found with skin rash (50%), diarrhoea (17.6%), mucositis (7%) and paronychia (3%). G5, possibly associated with pneumonitis might also have occurred. Poziotinib exhibited effects in mNSCLC patients with EGFR/HER2-exon 20-i-mut. The toxicity rate was high leading to frequent dose interruption and reduction, thereby reducing mPFS in patients with good ORR/DCR. ZENITH20 trial is now being used to evaluate the low dose and new scheduled dose (e.g. bis in die (BID)). •Treatment of NSCLC patients with EGFR and HER2 exon 20 insertion mutation remains an unmet clinical need.•Poziotinib is currently under investigation as a potential targeted therapy.•Poziotinib demonstrated clinical activity in NSCLC.•Poziotinib rate was high leading to frequent dose interruption.•Poziotinib dose below 16 mg or a new scheduled dose (e.g. BID) with a high rate of tolerance.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2021.02.038