Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With EGFR-Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study.
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Embargo End Date
ICR Authors
Authors
Yang, JC-H
Reckamp, KL
Kim, Y-C
Novello, S
Smit, EF
Lee, J-S
Su, W-C
Akerley, WL
Blakely, CM
Groen, HJM
Bazhenova, L
Carcereny Costa, E
Chiari, R
Hsia, T-C
Golsorkhi, T
Despain, D
Shih, D
Popat, S
Wakelee, H
Reckamp, KL
Kim, Y-C
Novello, S
Smit, EF
Lee, J-S
Su, W-C
Akerley, WL
Blakely, CM
Groen, HJM
Bazhenova, L
Carcereny Costa, E
Chiari, R
Hsia, T-C
Golsorkhi, T
Despain, D
Shih, D
Popat, S
Wakelee, H
Document Type
Journal Article
Date
2021-02-01
Date Accepted
2020-10-16
Abstract
INTRODUCTION: The TIGER-3 (NCT02322281) study was initiated to compare the efficacy and safety of rociletinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) that targets EGFR T790M and common EGFR-activating mutations, versus chemotherapy in patients with NSCLC who progressed on first- or second-generation EGFR TKIs. METHODS: Patients with advanced or metastatic EGFR-mutated NSCLC with disease progression on standard therapy (previous EGFR TKI and platinum-based chemotherapy) were randomized to oral rociletinib (500 or 625 mg twice daily) or single-agent chemotherapy (pemetrexed, gemcitabine, docetaxel, or paclitaxel). RESULTS: Enrollment was halted when rociletinib development was discontinued in 2016. Of 149 enrolled patients, 75 were randomized to rociletinib (n = 53: 500 mg twice daily; n = 22: 625 mg twice daily) and 74 to chemotherapy. The median investigator-assessed progression-free survival (PFS) was 4.1 months (95% confidence interval [CI]: 2.6-5.4) in the rociletinib 500-mg group and 5.5 months (95% CI: 1.8-8.1) in the 625-mg group versus 2.5 months (95% CI: 1.4-2.9) in the chemotherapy group. An improved PFS was observed in patients with T790M-positive NSCLC treated with rociletinib (n = 25; 500 mg and 625 mg twice daily) versus chemotherapy (n = 20; 6.8 versus 2.7 mo; hazard ratio = 0.55, 95% CI: 0.28-1.07, p = 0.074). Grade 3 or higher hyperglycemia (24.0%), corrected QT prolongation (6.7%), diarrhea (2.7%), and vomiting (1.3%) were more frequent with rociletinib than chemotherapy (0%, 0%, 1.4%, and 0%, respectively). CONCLUSIONS: Rociletinib had a more favorable median PFS versus chemotherapy but had higher rates of hyperglycemia and corrected QT prolongation in patients with advanced EGFR-mutated NSCLC who progressed on previous EGFR TKI. Incomplete enrollment prevented evaluation of the primary efficacy end point.
Citation
JTO Clinical and Research Reports, 2021, 2 (2), pp. 100114 -
Source Title
JTO Clinical and Research Reports
Publisher
ELSEVIER
ISSN
2666-3643
eISSN
2666-3643
2666-3643
2666-3643