Abstract
IntroductionJUNIPER 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.MethodsJUNIPER 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.ResultsBetween 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.ConclusionsIn 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
Highlights
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
KRAS is the most commonly mutated oncogene in nonsmall cell lung cancer (NSCLC), occurring mainly in lung adenocarcinomas (30%) and less frequently in squamous cell carcinoma (5%) [2, 3] Treatments directed toward KRAS mutations are not available because of limited efficacy resulting from failure to inhibit the protein directly, or inhibit its downstream effectors [4]
In the advanced/metastatic setting, prior chemotherapy was received in 98.9% of all randomized patients, targeted therapy in 26.5% of patients, and immunotherapy in Abemaciclib N = 270 Erlotinib N = 183
Summary
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. Irrespective of first-line response, patients with continued good performance status (PS) often proceed to second-line therapy [5, 6]. Such therapy yields an approximately 5- to 8-month overall survival (OS) for patients with KRAS mutation positive (KRAS+) NSCLC tumors [7,8,9]. Approvals of immune checkpoint inhibitors [nivolumab [14], pembrolizumab [15], and atezolizumab [16]] changed the standard of care in first-line therapy and after platinumbased treatment failure; these agents do not target patients with metastatic KRAS-mutated NSCLC, which continues to be an area of significant unmet medical need
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