TY - JOUR
T1 - Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer
AU - Dziadziuszko, Rafal
AU - Krebs, Matthew G.
AU - De Braud, Filippo
AU - Siena, Salvatore
AU - Drilon, Alexander
AU - Doebele, Robert C.
AU - Patel, Manish R.
AU - Cho, Byoung Chul
AU - Liu, Stephen V.
AU - Ahn, Myung-Ju
AU - Chiu, Chao-Hua
AU - Farago, Anna F.
AU - Lin, Chia-Chi
AU - Karapetis, Christos S.
AU - Li, Yu-Chung
AU - Day, Bann-Mo
AU - Chen, David
AU - Wilson, Timothy R.
AU - Barlesi, Fabrice
PY - 2021/4/10
Y1 - 2021/4/10
N2 - PURPOSE Genetic rearrangements of the tyrosine receptor kinase ROS proto-oncogene 1 (ROS1) are oncogenic drivers in non-small-cell lung cancer (NSCLC). We report the results of an updated integrated analysis of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of the ROS1 tyrosine kinase inhibitor, entrectinib, in ROS1 fusion–positive NSCLC. METHODS The efficacy-evaluable population included adults with locally advanced or metastatic ROS1 fusion–positive NSCLC with or without CNS metastases who received entrectinib $ 600 mg orally once per day. Co-primary end points were objective response rate (ORR) assessed by blinded independent central review and duration of response (DoR). Secondary end points included progression-free survival (PFS), overall survival (OS), intracranial ORR, intracranial DoR, intracranial PFS, and safety. RESULTS In total, 161 patients with a follow-up of $ 6 months were evaluable. The median treatment duration was 10.7 months (IQR, 6.4-17.7). The ORR was 67.1% (n 5 108, 95% CI, 59.3 to 74.3), and responses were durable (12-month DoR rate, 63%, median DoR 15.7 months). The 12-month PFS rate was 55% (median PFS 15.7 months), and the 12-month OS rate was 81% (median OS not estimable). In 24 patients with measurable baseline CNS metastases by blinded independent central review, the intracranial ORR was 79.2% (n 5 19; 95% CI, 57.9 to 92.9), the median intracranial PFS was 12.0 months (95% CI, 6.2 to 19.3), and the median intracranial DoR was 12.9 months (12-month rate, 55%). The safety profile in this updated analysis was similar to that reported in the primary analysis, and no new safety signals were found. CONCLUSION Entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion–positive NSCLC, including patients with CNS metastases.
AB - PURPOSE Genetic rearrangements of the tyrosine receptor kinase ROS proto-oncogene 1 (ROS1) are oncogenic drivers in non-small-cell lung cancer (NSCLC). We report the results of an updated integrated analysis of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of the ROS1 tyrosine kinase inhibitor, entrectinib, in ROS1 fusion–positive NSCLC. METHODS The efficacy-evaluable population included adults with locally advanced or metastatic ROS1 fusion–positive NSCLC with or without CNS metastases who received entrectinib $ 600 mg orally once per day. Co-primary end points were objective response rate (ORR) assessed by blinded independent central review and duration of response (DoR). Secondary end points included progression-free survival (PFS), overall survival (OS), intracranial ORR, intracranial DoR, intracranial PFS, and safety. RESULTS In total, 161 patients with a follow-up of $ 6 months were evaluable. The median treatment duration was 10.7 months (IQR, 6.4-17.7). The ORR was 67.1% (n 5 108, 95% CI, 59.3 to 74.3), and responses were durable (12-month DoR rate, 63%, median DoR 15.7 months). The 12-month PFS rate was 55% (median PFS 15.7 months), and the 12-month OS rate was 81% (median OS not estimable). In 24 patients with measurable baseline CNS metastases by blinded independent central review, the intracranial ORR was 79.2% (n 5 19; 95% CI, 57.9 to 92.9), the median intracranial PFS was 12.0 months (95% CI, 6.2 to 19.3), and the median intracranial DoR was 12.9 months (12-month rate, 55%). The safety profile in this updated analysis was similar to that reported in the primary analysis, and no new safety signals were found. CONCLUSION Entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion–positive NSCLC, including patients with CNS metastases.
KW - Entrectinib
KW - Metastatic ROS1
KW - Lung Cancer
KW - non-small-cell lung cancer
KW - ROS1 tyrosine kinase inhibitor
KW - ROS1 fusion–positive NSCLC
KW - NSCLC
UR - http://www.scopus.com/inward/record.url?scp=85104048194&partnerID=8YFLogxK
U2 - 10.1200/JCO.20.03025
DO - 10.1200/JCO.20.03025
M3 - Article
C2 - 33646820
AN - SCOPUS:85104048194
SN - 0732-183X
VL - 39
SP - 1253
EP - 1263
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -