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.; Mazières, Julien; Barlési, Fabrice; Dragnev, Konstantin H.; Koczywas, Marianna; Göskel, Tuncay; Cortot, A.; Girard, Nicolas; Wesseler, Claas; Bischoff, Helge; Nadal, Ernest; Park, Keunchil; Lü, Shun; Taus, Álvaro; Cobo, Manuel; Estrem, Shawn T.; Wijayawardana, Sameera R.; Turner, Kellie; Oakley, Gerard J.; Hurt, Karla; Chiang, Alan Y.; Hossain, Anwar; John, William J.; Paz‐Ares, Luis

doi:10.3389/fonc.2020.578756

Cited by 37 publications

(46 citation statements)

References 25 publications

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“…The most promising results were seen in breast cancer and non-small cell lung cancer (NSCLC) patients and prompted further studies. In the phase III JUNIPER study, previously chemotherapy treated patients with advanced stage NSCLC patients with KRAS mutations showed improved response rates and progression-free survival, which supports further investigations [74]. The MONARCH study series enrolled patients with hormone receptor positive, ErbB2-negative advanced breast cancer and led to FDA approval of abemaciclib as initial endocrine-based therapy in combination with an aromatase inhibitor [75].…”

Section: Resistance To Cdk4/6 Inhibitorsmentioning

confidence: 66%

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

2020

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Despite the development of targeted therapies and novel inhibitors, cancer remains an undefeated disease. Resistance mechanisms arise quickly and alternative treatment options are urgently required, which may be partially met by drug combinations. Protein kinases as signaling switchboards are frequently deregulated in cancer and signify vulnerable nodes and potential therapeutic targets. We here focus on the cell cycle kinase CDK6 and on the MAPK pathway and on their interplay. We also provide an overview on clinical studies examining the effects of combinational treatments currently explored for several cancer types.

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Section: Resistance To Cdk4/6 Inhibitorsmentioning

confidence: 66%

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

2020

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“…One identified target has been cyclin-dependent kinase (CDK) 4 [72]. In the phase III JUNIPER study (patients with KRAS-mutant NSCLC), the CDK4 inhibitor abemaciclib did not improve OS compared with erlotinib, a drug recognized to perform poorly in this setting [73]. Additionally, a recent UK study, the National Lung Matrix Trial, reported that only 1/30 patients with KRAS-mutant NSCLC showed a response to the CDK4/6 inhibitor palbociclib [74].…”

Section: A Brief History Of Kras Targetingmentioning

confidence: 99%

On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

et al. 2021

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…An ongoing Phase III clinical trial (JUNIPER) is evaluating the efficacy and safety of abemaciclib compared to erlotinib in previously treated patients with advanced KRAS -mutated NSCLC. The study did not meet its primary endpoint of OS but demonstrated an improvement in PFS and ORR [ 84 ].…”

Section: Krasmentioning

confidence: 99%

Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer

Rebuzzi

Zullo

Rossi

et al. 2021

IJMS

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In the scenario of systemic treatment for advanced non-small cell lung cancer (NSCLC) patients, one of the most relevant breakthroughs is represented by targeted therapies. Throughout the last years, inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-Ros oncogene 1 (ROS1), and V-raf murine sarcoma viral oncogene homolog B (BRAF) have been approved and are currently used in clinical practice. However, other promising molecular drivers are rapidly emerging as therapeutic targets. This review aims to cover the molecular alterations with a potential clinical impact in NSCLC, including amplifications or mutations of the mesenchymal–epithelial transition factor (MET), fusions of rearranged during transfection (RET), rearrangements of the neurotrophic tyrosine kinase (NTRK) genes, mutations of the Kirsten rat sarcoma viral oncogene (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), as well as amplifications or mutations of human epidermal growth factor receptor 2 (HER2). Additionally, we summarized the current status of targeted agents under investigation for such alterations. This revision of the current literature on emerging molecular targets is needed as the evolving knowledge on novel actionable oncogenic drivers and targeted agents is expected to increase the proportion of patients who will benefit from tailored therapeutic approaches.

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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

Cited by 37 publications

References 25 publications

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer

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