Icahn School of Medicine at Mount Sinai, New York, NY
Rima Patel , Nadeem Bilani , Amy Tiersten , Joseph A. Sparano
Background: The monarchE trial found that the addition of adjuvant abemaciclib to endocrine therapy in pts with lymph node (LN)+, HR+ EBC improved invasive disease-free survival in two pt cohorts: (1) ≥ 4 +LNs or 1-3 +LNs and Grade 3 disease or tumor ≥ 5 centimeters and (2) 1-3 +LNs and Ki67 ≥ 20%. The FDA approved adjuvant abemaciclib only in pts with HR+, HER2-negative, LN+ EBC with Ki67 ≥ 20%. The role of Ki67 as a predictive biomarker in this setting is unclear. ASCO guidelines recommend offering abemaciclib to pts who meet eligibility for either cohort and not restricting inclusion by Ki67. The objectives of this study were to (1) determine the association between Ki67 and the 21-gene recurrence score (RS), an established prognostic and predictive biomarker, using Ki67 cutoff ≥ 20% and (2) compare eligibility for adjuvant abemaciclib by FDA versus ASCO criteria. Methods: Women with HR+, HER2-negative EBC with 1-3 +LNs, diagnosed between 2018 and 2019, and who had available information on Ki67 and RS in the National Cancer Database were identified. Pts were categorized into Ki67 low ( < 20%) or high ( ≥ 20%) based on cutoff used in the monarchE and stratified by RS of low-intermediate (0-25) or high (26-100). Stratified agreement between Ki67 and RS were assessed using the proportion of agreement and Kappa statistic. McNemar’s test was used to compare proportion of pts eligible for abemaciclib by FDA versus ASCO criteria. Results: 5,137 eligible women were included. 61.1% (n = 3,140) had Ki67 < 20% and 38.9% (n = 1,997) Ki67 ≥ 20%. There was fair agreement (Kappa 0.21-0.40) between Ki67 and RS, which was statistically significant (Kappa = 0.25, p < 0.001). Overall, using the FDA criteria for abemaciclib, 38.9% (n = 1,997) of patients would be eligible while based on ASCO criteria, 43.5% (n = 2,235) could be offered adjuvant abemaciclib (p < 0.001). Among the 2,235 patients eligible for abemaciclib based on ASCO criteria, 57.0% (n = 1,273) were eligible due to Ki67 ≥ 20% alone, 10.6% (n = 238) due to Grade 3 alone, while 32.3% (n = 724) satisfied both Ki67 ≥ 20% and Grade 3 criteria. There were 3,431 patients who were post-menopausal with RS 0-25 and would be spared chemotherapy, yet 35.3% (n = 1,212) would be eligible for adjuvant abemaciclib based on FDA or ASCO criteria. Conclusions: There was only fair agreement between Ki67 and RS in patients with 1-3 +LNs based on Ki67 cutoff of 20%. Among patients with LN+ EBC, more patients would be offered abemaciclib using ASCO criteria compared to FDA criteria. Most were eligible for abemaciclib based on Ki67 alone, suggesting that Ki67 may provide additional information beyond tumor grade. In postmenopausal women with 1-3 +LNs, about 30% may be spared adjuvant chemotherapy based on the RS but still be sufficiently high risk to be considered for adjuvant abemaciclib.
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