Dataset Information

Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer.

ABSTRACT:

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.

SUBMITTER: Dziadziuszko R

PROVIDER: S-EPMC8078299 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic <i>ROS1</i> Fusion-Positive Non-Small-Cell Lung Cancer.

Dziadziuszko Rafal R Krebs Matthew G MG De Braud Filippo F Siena Salvatore S Drilon Alexander A Doebele Robert C RC Patel Manish R MR Cho Byoung Chul BC Liu Stephen V SV Ahn Myung-Ju MJ Chiu Chao-Hua CH Farago Anna F AF Lin Chia-Chi CC Karapetis Christos S CS Li Yu-Chung YC Day Bann-Mo BM Chen David D Wilson Timothy R TR Barlesi Fabrice F

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20210301 11

<h4>Purpose</h4>Genetic rearrangements of the tyrosine receptor kinase ROS proto-oncogene 1 (<i>ROS1</i>) 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 <i>ROS1</i> fusion-positive NSCLC.<h4>Methods</h4>The efficacy-evaluable population included adults with locally advanced or metastatic <i>ROS ...[more]

PMID: 33646820

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