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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

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,...

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Autores principales: Goldman, Jonathan W., Mazieres, Julien, Barlesi, Fabrice, Dragnev, Konstantin H., Koczywas, Marianna, Göskel, Tuncay, Cortot, Alexis B., Girard, Nicolas, Wesseler, Claas, Bischoff, Helge, Nadal, Ernest, Park, Keunchil, Lu, Shun, Taus, Alvaro, Cobo, Manuel, Estrem, Shawn T., Wijayawardana, Sameera R., Turner, Kellie, Oakley, Gerard Joseph, Hurt, Karla C., Chiang, Alan Y., Hossain, Anwar M., John, William J., Paz-Ares, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649422/
https://www.ncbi.nlm.nih.gov/pubmed/33194700
http://dx.doi.org/10.3389/fonc.2020.578756
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author Goldman, Jonathan W.
Mazieres, Julien
Barlesi, Fabrice
Dragnev, Konstantin H.
Koczywas, Marianna
Göskel, Tuncay
Cortot, Alexis B.
Girard, Nicolas
Wesseler, Claas
Bischoff, Helge
Nadal, Ernest
Park, Keunchil
Lu, Shun
Taus, Alvaro
Cobo, Manuel
Estrem, Shawn T.
Wijayawardana, Sameera R.
Turner, Kellie
Oakley, Gerard Joseph
Hurt, Karla C.
Chiang, Alan Y.
Hossain, Anwar M.
John, William J.
Paz-Ares, Luis
author_facet Goldman, Jonathan W.
Mazieres, Julien
Barlesi, Fabrice
Dragnev, Konstantin H.
Koczywas, Marianna
Göskel, Tuncay
Cortot, Alexis B.
Girard, Nicolas
Wesseler, Claas
Bischoff, Helge
Nadal, Ernest
Park, Keunchil
Lu, Shun
Taus, Alvaro
Cobo, Manuel
Estrem, Shawn T.
Wijayawardana, Sameera R.
Turner, Kellie
Oakley, Gerard Joseph
Hurt, Karla C.
Chiang, Alan Y.
Hossain, Anwar M.
John, William J.
Paz-Ares, Luis
author_sort Goldman, Jonathan W.
collection PubMed
description 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
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spelling pubmed-76494222020-11-13 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 Goldman, Jonathan W. Mazieres, Julien Barlesi, Fabrice Dragnev, Konstantin H. Koczywas, Marianna Göskel, Tuncay Cortot, Alexis B. Girard, Nicolas Wesseler, Claas Bischoff, Helge Nadal, Ernest Park, Keunchil Lu, Shun Taus, Alvaro Cobo, Manuel Estrem, Shawn T. Wijayawardana, Sameera R. Turner, Kellie Oakley, Gerard Joseph Hurt, Karla C. Chiang, Alan Y. Hossain, Anwar M. John, William J. Paz-Ares, Luis Front Oncol Oncology 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 Frontiers Media S.A. 2020-10-26 /pmc/articles/PMC7649422/ /pubmed/33194700 http://dx.doi.org/10.3389/fonc.2020.578756 Text en 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 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Goldman, Jonathan W.
Mazieres, Julien
Barlesi, Fabrice
Dragnev, Konstantin H.
Koczywas, Marianna
Göskel, Tuncay
Cortot, Alexis B.
Girard, Nicolas
Wesseler, Claas
Bischoff, Helge
Nadal, Ernest
Park, Keunchil
Lu, Shun
Taus, Alvaro
Cobo, Manuel
Estrem, Shawn T.
Wijayawardana, Sameera R.
Turner, Kellie
Oakley, Gerard Joseph
Hurt, Karla C.
Chiang, Alan Y.
Hossain, Anwar M.
John, William J.
Paz-Ares, Luis
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649422/
https://www.ncbi.nlm.nih.gov/pubmed/33194700
http://dx.doi.org/10.3389/fonc.2020.578756
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