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
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Jonathan W Goldman1, Julien Mazieres2, Fabrice Barlesi3
1Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States.
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.
Insights
Abemaciclib did not improve overall survival in patients with KRAS-mutated NSCLC compared to erlotinib. However, it significantly improved progression-free survival and response rates, suggesting potential for other NSCLC patient groups.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- JUNIPER trial investigated abemaciclib, a CDK4/6 inhibitor, versus erlotinib in advanced non-small cell lung cancer (NSCLC) with KRAS mutations.
- Patients had progressed on prior chemotherapy and one additional therapy, including immune checkpoint inhibitors.
Purpose of the Study:
- To compare the efficacy and safety of abemaciclib against erlotinib in patients with stage IV NSCLC and KRAS mutations.
- To evaluate overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety.
Main Methods:
- Phase III, multicenter, randomized, open-label trial (NCT02152631) with 453 patients randomized 3:2.
- Abemaciclib (200 mg BID) or erlotinib (150 mg QD) with best supportive care until progression or toxicity.
Main Results:
- Median OS was similar: 7.4 months (abemaciclib) vs. 7.8 months (erlotinib) (p=0.77).
- Median PFS significantly improved with abemaciclib (3.6 months vs. 1.9 months, p<0.000001).
- ORR was higher with abemaciclib (8.9% vs. 2.7%, p=0.010), with improved disease control rates.
Conclusions:
- Abemaciclib did not meet the primary endpoint of improved OS but demonstrated significant PFS and ORR benefits in KRAS-mutated NSCLC.
- The observed efficacy and manageable safety profile support further investigation of abemaciclib in NSCLC, potentially in combination therapies or other patient subgroups.
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