A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER

Jonathan W Goldman; Julien Mazieres; Fabrice Barlesi; Konstantin H Dragnev; Marianna Koczywas; Tuncay Göskel; Alexis B Cortot; Nicolas Girard; Claas Wesseler; Helge Bischoff; Ernest Nadal; Keunchil Park; Shun Lu; Alvaro Taus; Manuel Cobo; Shawn T Estrem; Sameera R Wijayawardana; Kellie Turner; Gerard Joseph Oakley 3rd; Karla C Hurt; Alan Y Chiang; Anwar M Hossain; William J John; Luis Paz-Ares

doi:10.3389/fonc.2020.578756

A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER

Front Oncol. 2020 Oct 26:10:578756. doi: 10.3389/fonc.2020.578756. eCollection 2020.

Authors

Jonathan W Goldman¹, Julien Mazieres², Fabrice Barlesi³, Konstantin H Dragnev⁴, Marianna Koczywas⁵, Tuncay Göskel⁶, Alexis B Cortot⁷, Nicolas Girard⁸, Claas Wesseler⁹, Helge Bischoff¹⁰, Ernest Nadal¹¹, Keunchil Park¹², Shun Lu¹³, Alvaro Taus¹⁴, Manuel Cobo¹⁵, Shawn T Estrem¹⁶, Sameera R Wijayawardana¹⁶, Kellie Turner¹⁶, Gerard Joseph Oakley 3rd¹⁶, Karla C Hurt¹⁶, Alan Y Chiang¹⁶, Anwar M Hossain¹⁶, William J John¹⁶, Luis Paz-Ares¹⁷

Affiliations

¹ Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States.
² Thoracic Oncology Department, Toulouse University Hospital, Paul Sabatier University, Toulouse, France.
³ Multidisciplinary Oncology and Innovative Therapies Department, Aix-Marseille University, INSERM, CNRS, CRCM, Assistance Publque Hôspitaux de Marseille (AP-HM), Marseille, France.
⁴ Department of Medicine, Norris Cotton Cancer Center, Dartmouth-Hitchcock, Lebanon, NH, United States.
⁵ Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA, United States.
⁶ Department of Internal Medical Sciences, Ege University, (Bornova), Izmir, Turkey.
⁷ Thoracic Oncology Department, University of Lille, CHU Lille, Lille, France.
⁸ Respiratory Medicine Department, Hospices Civils de Lyon, University of Lyon, Lyon, France.
⁹ Department of Thoracic Oncology, Asklepios Klinikum Harburg, Hamburg, Germany.
¹⁰ Department of Thoracic Oncology, Thoraxklinik-Heidelberg, Heidelberg, Germany.
¹¹ Department of Medical Oncology, Catalan Institute of Oncology, (L'Hospitalet), Barcelona, Spain.
¹² Department of Hematology-Oncology, Samsung Medical Center, Seoul, South Korea.
¹³ Lung Tumor Medical (Cancer) Center, Shanghai Chest Hospital, Shanghai (Jiao Tong University), Shanghai, China.
¹⁴ Department of Medical Oncology, Hospital del Mar, Barcelona, Spain.
¹⁵ Medical Oncology Department, Hospital Regional Universitario Málaga, IBIMA, Málaga, Spain.
¹⁶ Eli Lilly and Company, Indianapolis, IN, United States.
¹⁷ Department of Medicine, Hospital Universitario 12 de Octubre, CNIO and Universidad Complutense, Madrid, Spain.

Abstract

Introduction: JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma (KRAS) mutation.

Methods: JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the KRAS oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety.

Results: Between December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval [CI]: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio [HR] = 0.968 [95% CI: 0.768, 1.219]; p = .77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 [95% CI: 0.470, 0.723]; p <.000001). ORR was 8.9% and 2.7% (p = .010), and the disease control rate was 54.4% and 31.7% (p <.001) with abemaciclib and erlotinib, respectively. Safety results reflected the known safety profiles of abemaciclib and erlotinib.

Conclusions: In this study, the primary endpoint of OS was not met; PFS and ORR were improved with manageable toxicity in the abemaciclib arm. The increases in response rates and PFS support further investigation of abemaciclib in other NSCLC subpopulations or in combination with other agents.

Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT02152631.

Keywords: KRAS; NSCLC; abemaciclib; erloitinib; platinum-resistant.

Copyright © 2020 Goldman, Mazieres, Barlesi, Dragnev, Koczywas, Göskel, Cortot, Girard, Wesseler, Bischoff, Nadal, Park, Lu, Taus, Cobo, Estrem, Wijayawardana, Turner, Oakley, Hurt, Chiang, Hossain, John and Paz-Ares.

Associated data

ClinicalTrials.gov/NCT02152631