Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With EGFR-Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study
Year: 2020
Type: article
Study design: Clinical Trial
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.
Authors: James Chih-Hsin Yang, Karen L. Reckamp, Young-Chul Kim, Silvia Novello, Egbert F. Smit, Jong-Seok Lee, Wu-Chou Su, Wallace L. Akerley, Collin M. Blakely, Harry J.M. Groen, Lyudmila Bazhenova, Enric Carcereny Costa, Rita Chiari, Te-Chun Hsia, Tony Golsorkhi, Darrin Despain, Danny Shih, Sanjay Popat, Heather Wakelee
Institutions: National Taiwan University Hospital, Cedars-Sinai Medical Center, Chonnam National University Hwasun Hospital, Ospedale San Luigi Gonzaga, University of Turin, The Netherlands Cancer Institute, Seoul National University, Seoul National University Bundang Hospital, National Cheng Kung University Hospital, Huntsman Cancer Institute, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, University Medical Center Groningen, University of Groningen, Moores Cancer Center, Institut Català d'Oncologia, China Medical University, China Medical University Hospital, China Medical University, Clovis Oncology (United States), Royal Marsden NHS Foundation Trust, Royal Marsden Hospital, Stanford Medicine, Stanford University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
Funders: Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Novartis, Roche, Celgene, AbbVie, Takeda Pharmaceuticals U.S.A., Helsinn, Takeda Pharmaceutical Company, Exelixis, TG Therapeutics, Clovis Oncology, Genentech, EMD Serono, Merck Sharp and Dohme, Chugai Pharmaceutical, Pharmaceuticals Bayer, Daiichi Sankyo Europe
OpenAlex ID: W3096198440