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; 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

doi:10.1016/j.jtocrr.2020.100114

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

JTO Clin Res Rep. 2020 Oct 26;2(2):100114. doi: 10.1016/j.jtocrr.2020.100114. eCollection 2021 Feb.

Authors

James Chih-Hsin Yang¹, Karen L Reckamp², Young-Chul Kim³, Silvia Novello⁴, Egbert F Smit⁵, Jong-Seok Lee⁶, Wu-Chou Su⁷, Wallace L Akerley⁸, Collin M Blakely⁹, Harry J M Groen¹⁰, Lyudmila Bazhenova¹¹, Enric Carcereny Costa¹², Rita Chiari¹³, Te-Chun Hsia¹⁴, Tony Golsorkhi¹⁵, Darrin Despain¹⁶, Danny Shih¹⁷, Sanjay Popat¹⁸, Heather Wakelee¹⁹

Affiliations

¹ Department of Oncology, National Taiwan University Hospital, Taipei City, Republic of China.
² Department of Medical Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
³ Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeollanam-do, Republic of Korea.
⁴ Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano, Italy.
⁵ Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
⁶ Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
⁷ Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City, Republic of China.
⁸ Medical Oncology, Huntsman Cancer Institute, Salt Lake City, Utah.
⁹ Division of Hematology/Oncology, Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
¹⁰ Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
¹¹ Division of Hematology and Medical Oncology, University of California San Diego Moores Cancer Center, La Jolla, California.
¹² Medical Oncology Department, Catalan Institute of Oncology Badalona, Badalona Applied Research Group in Oncology, Badalona, Spain.
¹³ Medical Oncology, AULSS6 Euganea-Ospedali Riuniti Padova Sud, Padua, Italy.
¹⁴ Department of Respiratory Therapy, China Medical University, China Medical University Hospital, Taichung City, Republic of China.
¹⁵ Clinical Development, Clovis Oncology, Inc., Boulder, Colorado.
¹⁶ Biostatistics, Clovis Oncology, Inc., Boulder, Colorado.
¹⁷ Clinical Operations, Clovis Oncology, Inc., Boulder, Colorado.
¹⁸ Lung Unit, The Royal Marsden Hospital, Royal Marsden NHS Foundation Trust, London, United Kingdom.
¹⁹ Division of Oncology, Department of Medicine, Stanford University, Stanford, California.

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.

Keywords: EGFR tyrosine kinase inhibitor; Epidermal growth factor receptor mutations; Non–small cell lung cancer; Phase III randomized clinical trial; Rociletinib.