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Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 & 6i) provide significant benefit for patients (pts) with HR+, HER2- MBC, however, clinical questions remain regarding the optimal sequence (seq) of treatments (tx). Prior analyses of real world (rw) abemaciclib indicate up to 50% of pts have had prior palbociclib or ribociclib for MBC and published studies regarding seq and non-seq tx outcomes have had limited sample sizes. To our knowledge, the current study represents the largest rw analysis of CDK4 & 6i tx seq to date. Methods: US electronic medical records were retrospectively analyzed from the ConcertAI Oncology Dataset. Pts received abemaciclib and ≥ 1 other systemic tx line for HR+, HER2- MBC; the study period was 11/1995 (date of first MBC dx in dataset) to 10/2020 (end of follow-up). Tx sequences were identified and grouped to enable outcomes analyses. Data for 4 select groups (grp) are presented: grp 1 (1L CDK4 & 6i to 2L CDK4 & 6i), grp 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), grp 3 (2L CDK4 & 6i to 3L CDK4 & 6i), grp 4 (2L CDK4 & 6i to 3L non- CDK4 & 6i). Progression-free survival (PFS) from regimen start date to disease progression or death was analyzed by line using Kaplan-Meier method; pts were censored on the start date of the subsequent tx or end of follow-up if a progression event was not reported. Pts were characterized as having primary or secondary endocrine resistance per ESMO guidelines, if applicable. Pt characteristics at initiation of 1st CDK4 & 6i and median PFS are summarized descriptively. Results: Of 690pts, the majority were white (n=555, 80%), had a median age of 61yrs (range 26-86) and were treated in community oncology practices (80%) in southern US (47%). Most pt characteristics between grp 1 vs grp 2 were not statistically different except for pts participating in clinical trials [grp 1 (n=3; 2%) vs grp 2 (n=12; 13%)]. Pts in grp 4 were younger than grp 3, with a median age of 60 and 67yrs, respectively (p<0.05). In the overall cohort, the most prevalent tx seq grp was 1L CDK4 & 6i followed by 2L CDK4 & 6i (n=165). There was significant treatment regimen heterogeneity across all grps, with the most frequent being 1L palbociclib/AI followed by 2L abemaciclib/fulvestrant received by 26 (16%) pts. Abemaciclib was prevalent in 1L (n=92; 13%), 2L (n= 204; 30%), 3L (n=122; 18%), ≥4L (n=344; 50%). Pts receiving seq CDK4 & 6i experienced a substantial PFS benefit in the subsequent line (grp 1: 17mo; grp 3: 11mo), while pts in non-seq grps experienced a numerically lower PFS from the non-CDK4 & 6i tx in the subsequent line (grp 2: 8mo; grp 4: 8mo). Median PFS for each grp is described in Table 1. Results of cox proportional hazards models will be presented.

Conclusions: Seq CDK4 & 6i appears to deliver substantial 2L PFS in pts who had a meaningful PFS on 1L CDK4 & 6i. These results appear consistent for pts receiving 3L CDK4 & 6i who had a meaningful PFS to 2L CDK4 & 6i. While most pts received 1L CDK4 & 6i to 2L CDK4 & 6i, there was marked tx heterogeneity across all seqs in this predominantly community oncology sample, reinforcing the continued lack of consensus on this topic. While these results are hypothesis generating, these data serve as further rationale for additional prospective and retrospective studies evaluating the potential utilization and outcomes of CDK4 & 6i, after progression on a previous CDK4 & 6i.

Table 1.

Grp 11L CDK4 & 6i to 2L CDK4 & 6i n=165Grp 21L CDK4 & 6ito 2L non-CDK4 & 6i n=94Grp 32L CDK4 & 6i to 3L CDK4 & 6i n=115Grp 42L CDK4 & 6i to 3L non-CDK4 & 6i n=121
Line 1     
No. of Events/Pts 78/165 72/94   
Median (m) 18.45 9.80   
95% CI [15.0, 23.2] [6.4, 14.2]   
Line 2     
No. of Events/Pts 55/165 40/94 55/115 87/121 
Median (m) 17.30 8.39 17.30 8.29 
95% CI [9.8, 33.4] [5.9, 10.5] [12.1, 21.0] [6.2, 9.9] 
Line 3     
No. of Events/Pts   46/115 57/121 
Median (m)   11.22 7.86 
95% CI   [6.8, 14.0] [5.5, 11.3] 
Grp 11L CDK4 & 6i to 2L CDK4 & 6i n=165Grp 21L CDK4 & 6ito 2L non-CDK4 & 6i n=94Grp 32L CDK4 & 6i to 3L CDK4 & 6i n=115Grp 42L CDK4 & 6i to 3L non-CDK4 & 6i n=121
Line 1     
No. of Events/Pts 78/165 72/94   
Median (m) 18.45 9.80   
95% CI [15.0, 23.2] [6.4, 14.2]   
Line 2     
No. of Events/Pts 55/165 40/94 55/115 87/121 
Median (m) 17.30 8.39 17.30 8.29 
95% CI [9.8, 33.4] [5.9, 10.5] [12.1, 21.0] [6.2, 9.9] 
Line 3     
No. of Events/Pts   46/115 57/121 
Median (m)   11.22 7.86 
95% CI   [6.8, 14.0] [5.5, 11.3] 

Citation Format: Kevin M Kalinsky, Megan Kruse, Emily Nash Smyth, Claudia M Guimaraes, Santosh Gautam, Alnecia R Nisbett, Maxine D Fisher, Zhanglin Lin Cui, Lee Bowman. Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 and 6i for HR+, HER2- MBC in the real world [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-37.

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