TY - JOUR
T1 - Phase 2 Study of Talazoparib in Patients With Homologous Recombination Repair–Deficient Squamous Cell Lung Cancer
T2 - Lung-MAP Substudy S1400G
AU - Owonikoko, Taofeek K.
AU - Redman, Mary W.
AU - Byers, Lauren A.
AU - Hirsch, Fred R.
AU - Mack, Philip C.
AU - Schwartz, Lawrence H.
AU - Bradley, Jeffrey D.
AU - Stinchcombe, Thomas E.
AU - Leighl, Natasha B.
AU - Al Baghdadi, Tareq
AU - Lara, Primo
AU - Miao, Jieling
AU - Kelly, Karen
AU - Ramalingam, Suresh S.
AU - Herbst, Roy S.
AU - Papadimitrakopoulou, Vassiliki
AU - Gandara, David R.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/5
Y1 - 2021/5
N2 - Purpose: This signal finding study (S1400G) was designed to evaluate the efficacy of talazoparib in advanced stage squamous cell lung cancer harboring homologous recombination repair deficiency. Patients and Methods: The full eligible population (FEP) had tumors with a deleterious mutation in any of the study-defined homologous recombination repair genes and without prior exposure to a PARP inhibitor. The primary analysis population (PAP) is a subset of FEP with alteration in ATM, ATR, BRCA1, BRCA2, or PALB2. Treatment consisted of talazoparib 1 mg daily continuously in 21-day cycles. A 2-stage design with exact 93% power and 1-sided 0.07 type I error required enrollment of 40 patients in the PAP in order to rule out an overall response rate (ORR) of 15% or less if the true ORR is ≥ 35%. Results: The study enrolled 47 patients in the FEP, of whom 24 were in the PAP. The median age for the FEP was 66.7 years; 83% were male and 85% white. ORR in the PAP was 4% (95% confidence interval [CI], 0, 21) with disease control rate of 54% (95% CI, 33, 74). Median progression-free survival and overall survival were 2.4 months (95% CI, 1.5-2.8) and 5.2 months (95% CI, 4.0-10), respectively. In the FEP, ORR was 11% (95% CI, 3.6, 23), the disease control rate was 51% (95% CI, 36, 66), and the median duration of response was 1.8 months (95% CI, 1.3, 4.2). Median progression-free and overall survival were 2.5 months and 5.7 months, respectively. Conclusions: S1400G failed to show sufficient level of efficacy for single agent talazoparib in a biomarker defined subset of squamous lung cancer with homologous recombination repair deficiency.
AB - Purpose: This signal finding study (S1400G) was designed to evaluate the efficacy of talazoparib in advanced stage squamous cell lung cancer harboring homologous recombination repair deficiency. Patients and Methods: The full eligible population (FEP) had tumors with a deleterious mutation in any of the study-defined homologous recombination repair genes and without prior exposure to a PARP inhibitor. The primary analysis population (PAP) is a subset of FEP with alteration in ATM, ATR, BRCA1, BRCA2, or PALB2. Treatment consisted of talazoparib 1 mg daily continuously in 21-day cycles. A 2-stage design with exact 93% power and 1-sided 0.07 type I error required enrollment of 40 patients in the PAP in order to rule out an overall response rate (ORR) of 15% or less if the true ORR is ≥ 35%. Results: The study enrolled 47 patients in the FEP, of whom 24 were in the PAP. The median age for the FEP was 66.7 years; 83% were male and 85% white. ORR in the PAP was 4% (95% confidence interval [CI], 0, 21) with disease control rate of 54% (95% CI, 33, 74). Median progression-free survival and overall survival were 2.4 months (95% CI, 1.5-2.8) and 5.2 months (95% CI, 4.0-10), respectively. In the FEP, ORR was 11% (95% CI, 3.6, 23), the disease control rate was 51% (95% CI, 36, 66), and the median duration of response was 1.8 months (95% CI, 1.3, 4.2). Median progression-free and overall survival were 2.5 months and 5.7 months, respectively. Conclusions: S1400G failed to show sufficient level of efficacy for single agent talazoparib in a biomarker defined subset of squamous lung cancer with homologous recombination repair deficiency.
KW - Biomarker
KW - Non–small-cell lung cancer
KW - PARP
KW - Post-frontline
KW - Targeted therapy
KW - Trial
UR - http://www.scopus.com/inward/record.url?scp=85100763032&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100763032&partnerID=8YFLogxK
U2 - 10.1016/j.cllc.2021.01.001
DO - 10.1016/j.cllc.2021.01.001
M3 - Article
C2 - 33583720
AN - SCOPUS:85100763032
SN - 1525-7304
VL - 22
SP - 187-194.e1
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 3
ER -