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, 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

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.

Figures

Figure 1
Figure 1
(A) Study design of JUNIPER Phase III clinical trial. (B) Patient disposition (CONSORT) diagram. KRAS, Kirsten rat sarcoma; N, number of patients; NSCLC, non-small cell lung cancer; Q12H, every 12 hours; Q24H, every 24 hours.
Figure 2
Figure 2
Overall survival (OS) and progression-free survival (PFS) in the ITT population. (A) Kaplan-Meier curve of OS. (B) Forest plot of OS subgroup analyses. (C) Kaplan-Meier curve of PFS. (D) Forest plot of PFS subgroup analyses. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; ITT, intent-to-treat; KRAS, Kirsten rat sarcoma.
Figure 3
Figure 3
Response to treatment (ITT population). (A) Maximum percent change from baseline in tumor size in individual patients: top, abemaciclib; bottom, erlotinib. (B) Percent change from baseline in tumor size in individual patients over the course of treatment: (top) abemaciclib; (bottom) erlotinib. (C) Table of best overall responses by treatment. CI, confidence interval; ITT, intent-to-treat; mo, months; NE, non-evaluable; PD, progressive disease.

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