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 - Chul Cho, Byoung
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
N1 - Funding Information:
Supported by F. Hoffmann-La Roche Ltd.
Funding Information:
The authors thank the patients, their families, and the participating study centers. We also acknowledge the valuable contribution of Harald Zeuner to this manuscript. Third-party medical writing assistance, under the direction of the authors, was provided by Lewis Cawkwell, PhD, of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd. Matthew Krebs acknowledges support from National Institute for Health Research (NIHR) Manchester Biomedical Research Centre and NIHR Manchester Clinical Research Facility at The Christie and Manchester Experimental Cancer Medicine Centre (Manchester, United Kingdom).
Publisher Copyright:
© 2021 by American Society of Clinical Oncology Creative Commons Attribution Non-Commercial No Derivatives 4.0 License
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 = 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 = 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 = 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 = 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.
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 -
