TY - JOUR
T1 - Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations
T2 - ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)
AU - ZENITH20-4 Investigators
AU - Cornelissen, Robin
AU - Prelaj, Arsela
AU - Sun, Sophie
AU - Baik, Christina
AU - Wollner, Mirjana
AU - Haura, Eric B.
AU - Mamdani, Hirva
AU - Riess, Jonathan W.
AU - Cappuzzo, Federico
AU - Garassino, Marina C.
AU - Heymach, John V.
AU - Socinski, Mark A.
AU - Leu, Szu Yun
AU - Bhat, Gajanan
AU - Lebel, Francois
AU - Le, Xiuning
N1 - Publisher Copyright:
© 2023
PY - 2023/8
Y1 - 2023/8
N2 - Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions. Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety. Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%–50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%–82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6–11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4–7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%). Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.
AB - Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions. Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety. Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%–50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%–82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6–11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4–7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%). Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.
KW - Exon 20 mutations
KW - HER2
KW - Non–small cell lung cancer (NSCLC)
KW - Poziotinib
KW - Tyrosine kinase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85153586995&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85153586995&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2023.03.016
DO - 10.1016/j.jtho.2023.03.016
M3 - Article
C2 - 36958688
AN - SCOPUS:85153586995
SN - 1556-0864
VL - 18
SP - 1031
EP - 1041
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 8
ER -