A multicenter analysis of abemaciclib after progression on palbociclib in patients (pts) with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC).

Abstract

1057 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are widely used for pts with HR+/HER2- MBC. The MONARCH-1 trial of abemaciclib monotherapy in pre-treated pts demonstrated a median progression free survival (PFS) of 6.0 months, leading to approval as monotherapy in a CDK4/6i-naïve population. There are no data on abemaciclib in HR+/HER2- MBC after progressive disease (PD) with CDK4/6i. Methods: We evaluated clinical outcomes in pts with HR+/HER2- MBC who received abemaciclib following PD on prior palbociclib or ribociclib at 4 US academic centers. We conducted genomic analysis utilizing next-generation sequencing of tissue samples and blood (cell-free/cfDNA) when available. Results: From 2/2015 through 1/2019, 58 pts with HR+/HER2- MBC received abemaciclib following PD on prior palbociclib. 20 pts (34%) received sequential courses of therapy, while 38 pts (66%) had at least one intervening non-CDK4/6i regimen. 14 pts (24%) received abemaciclib monotherapy and 44 pts (76%) received it in combination with an antiestrogen, including fulvestrant (52%), an aromatase inhibitor (22%), and tamoxifen (2%). 22 pts (38%) required dose reduction, while 7 (12%) discontinued due to toxicity. At data cutoff (1/23/2019), 20 pts (34%) had early PD (duration < 90 days), while 21 pts (36%) had treatment duration exceeding 6 months, including 10 who remain on treatment at interim analysis (range 181-413 days). The median PFS was 5.8 months (95%CI 3.4 – 8.0). Preliminary analysis of cfDNA revealed RB1 and FGFR1 alterations in pts with PD on abemaciclib. Additional analyses with mature clinical data and genomic sequencing will be provided at the meeting. Conclusions: This is the first multi-center experience to demonstrate that a substantial proportion of pts continue to derive clinical benefit with abemaciclib after prior CDK4/6i, highlighting the potential for its use following CDK4/6 blockade. A second subset had early progression, suggesting cross-resistance to CDK4/6i via common pathways. Future effort should be directed towards validating potential biomarkers to guide optimal utilization of continued CDK4/6 blockade in HR+/HER2- MBC.

Letrozole and Palbociclib in Advanced Breast Cancer: Outcome from Cancer Institute, Chennai

“…Currently, there is no standard therapy for patients who progress on letrozole and palbociclib. The options can be alpelisib and fulvestrant in PIK3CA-mutated tumors, [19] abemaciclib, [20] exemestane everolimus, [21] fulvestrant, or chemotherapy. Enrollment in clinical trials could be an option in view of lack of standard treatment.…”

CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives

“…In this study, 20 patients (34%) received sequential courses of therapy, and 38 patients (66%) had at least one intervening non-CDK4/6 inhibitor regimen. Fourteen patients (24%) received abemaciclib monotherapy and 44 patients (76%) received abemaciclib in combination with an anti-estrogen, including fulvestrant (52%), an aromatase inhibitor (22%), and tamoxifen (2%) [ 39 ]. In this analysis, 20 patients (34%) had early disease progression (duration < 90 days), whereas 21 patients (36%) had treatment duration exceeding 6 months, including 10 who remained on treatment at the interim analysis (range, 181–413 days).…”

Response to Abemaciclib After 10 Lines of Therapy Including Palbociclib in Metastatic Breast Cancer: A Case Report With Literature Review

“…Since our patient maintained a good performance status and desired more therapy after four HT regimens, including letrozole and palbociclib, and more than five chemotherapy regimens, it seemed reasonable to try abemaciclib due to lack of other good options and a significant interval since prior exposure to a CDK4/6 inhibitor. Since the patient started this therapy, additional data emerged from multiple institutions indicating activity of abemaciclib after failure of palbociclib in a prior line of therapy [12][13][14][15] as summarized in Table 2. The purpose of this report is to raise awareness about this option and to allude to this lack of complete cross-resistance between the two CDK4/6 inhibitors.…”

“…Three pts had recently initiated abemaciclib therapy (less than 120 days prior to the current analysis). A subset of pts derived clinical benefit with continued exposure to CDK4/6i Wander et al 2019 [ 13 ] Evaluated clinical outcomes in pts with HR+/HER2− MBC who received abemaciclib following progression on prior palbociclib at four US academic centers Twenty-one pts (36%) had abemaciclib treatment duration exceeding 6 months (alone or combined), including 10 who remained on treatment at interim analysis (range 181–413 days). This is the first multi-center experience demonstrating a substantial proportion of pts with clinical benefit with abemaciclib after prior CDK4/6i exposure Tamragouri et al 2019 [ 14 ] Performed a chart review of pts with HR+, HER2− MBC who progressed on palbociclib and were subsequently treated with abemaciclib with or without fulvestrant Twenty-one pts were included.…”