Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With EGFR-Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study

James Chih-Hsin Yang, MD, PhD; Karen L. Reckamp, MD; Young-Chul Kim, MD, PhD; Silvia Novello, MD, PhD; Egbert F. Smit, MD, PhD; Jong-Seok Lee, MD, PhD; Wu-Chou Su, MD; Wallace L. Akerley, MD; Collin M. Blakely, MD, PhD; Harry J.M. Groen, MD, PhD; Lyudmila Bazhenova, MD; Enric Carcereny Costa, MD; Rita Chiari, MD, PhD; Te-Chun Hsia, MD, PhD; Tony Golsorkhi, MD; Darrin Despain, MStat; Danny Shih, BA; Sanjay Popat, BSc, MBBS, FRCP, PhD; Heather Wakelee, MD

JTO Clinical and Research Reports (Feb 2021)

Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With EGFR-Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study

James Chih-Hsin Yang, MD, PhD,
Karen L. Reckamp, MD,
Young-Chul Kim, MD, PhD,
Silvia Novello, MD, PhD,
Egbert F. Smit, MD, PhD,
Jong-Seok Lee, MD, PhD,
Wu-Chou Su, MD,
Wallace L. Akerley, MD,
Collin M. Blakely, MD, PhD,
Harry J.M. Groen, MD, PhD,
Lyudmila Bazhenova, MD,
Enric Carcereny Costa, MD,
Rita Chiari, MD, PhD,
Te-Chun Hsia, MD, PhD,
Tony Golsorkhi, MD,
Darrin Despain, MStat,
Danny Shih, BA,
Sanjay Popat, BSc, MBBS, FRCP, PhD,
Heather Wakelee, MD

Affiliations

James Chih-Hsin Yang, MD, PhD: Department of Oncology, National Taiwan University Hospital, Taipei City, Republic of China
Karen L. Reckamp, MD: Department of Medical Oncology, Cedars-Sinai Medical Center, Los Angeles, California
Young-Chul Kim, MD, PhD: Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeollanam-do, Republic of Korea
Silvia Novello, MD, PhD: Department of Oncology, University of Turin, Azienda Ospedaliero–Universitaria San Luigi Gonzaga, Orbassano, Italy
Egbert F. Smit, MD, PhD: Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Jong-Seok Lee, MD, PhD: Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
Wu-Chou Su, MD: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City, Republic of China
Wallace L. Akerley, MD: Medical Oncology, Huntsman Cancer Institute, Salt Lake City, Utah
Collin M. Blakely, MD, PhD: Division of Hematology/Oncology, Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California
Harry J.M. Groen, MD, PhD: Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
Lyudmila Bazhenova, MD: Division of Hematology and Medical Oncology, University of California San Diego Moores Cancer Center, La Jolla, California
Enric Carcereny Costa, MD: Medical Oncology Department, Catalan Institute of Oncology Badalona, Badalona Applied Research Group in Oncology, Badalona, Spain
Rita Chiari, MD, PhD: Medical Oncology, AULSS6 Euganea–Ospedali Riuniti Padova Sud, Padua, Italy
Te-Chun Hsia, MD, PhD: Department of Respiratory Therapy, China Medical University, China Medical University Hospital, Taichung City, Republic of China
Tony Golsorkhi, MD: Clinical Development, Clovis Oncology, Inc., Boulder, Colorado
Darrin Despain, MStat: Biostatistics, Clovis Oncology, Inc., Boulder, Colorado
Danny Shih, BA: Clinical Operations, Clovis Oncology, Inc., Boulder, Colorado
Sanjay Popat, BSc, MBBS, FRCP, PhD: Lung Unit, The Royal Marsden Hospital, Royal Marsden NHS Foundation Trust, London, United Kingdom
Heather Wakelee, MD: Division of Oncology, Department of Medicine, Stanford University, Stanford, California; Corresponding author. Address for correspondence: Heather Wakelee, MD, Division of Oncology, Department of Medicine, Stanford University, 875 Blake Wilbur Dr., Rm 2233, Stanford, CA 94305.

Journal volume & issue: Vol. 2, no. 2
p. 100114

Abstract

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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.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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