494P - Proviral insertion in murine 1 (PIM1) kinase expression and clinical outcomes in advanced breast cancer (ABC)

Background

Prior and current data has shown PIM1 Kinase Expression (PIM1) in renal cell carcinoma (RCC) is associated with a poor prognosis.¹ CDK4/6 inhibitor (CDK4/6i) abemaciclib (A), but not palbociclib (P) may specifically target PIM1.² Given the differential efficacy of CDK4/6i in ABC without a biomarker beyond hormone receptor (HR+), we explored the relationship between PIM1 and patient outcomes. 1 An Analysis of PIM1 Kinase Expression and Clinical Outcomes in Renal Cell Carcinoma (RCC) Holder SL, et al. ESMO Congress 2023 Submission #2301 2 Small J, et al. Addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors. Oncotarget. 2017 Jul 27;8(56):95116-95134.

Methods

Whole transcriptome sequencing (WTS) data in Caris Life Sciences real-world database breast cancer (BC) patient tumors were stratified by PIM1 expression quartiles and BC subtypes (HR+ and triple negative (TN]). Overall survival (OS; defined as time from diagnosis to last contact or death) and time on treatment (TOT) were obtained from insurance claims data.

Results

In 8,104 BC tumors, high PIM1 (Q4) had worse OS (27.3 mos) compared to low PIM1 (Q1, 41.9 mos). Median PIM1 transcripts were higher in TNBC vs HR+ (7.93 vs 4.46). In HR+ ABC, PIM1 Q4 was associated with different co-mutation frequencies (Table) and worse OS (Q1 57.7 vs Q4 45.3 mos, HR 1.28 95%CI=1.03-1.58 p=0.023). In TN ABC, PIM1 quartiles had similar co-mutation profiles, and no OS difference was noted (Q1 23.8 vs Q4 26.1 mos, HR=1.06 95%CI: 0.83-1.35 p=0.67). In HR+, PIM1 Q4 had significantly shorter TOT for A only (5.6 vs 2.6 mos, HR=1.68 95%CI: 0.99-2.82 p=0.049), no difference with P or R.

Table: 494P

Co-mutation frequencies in hormone receptor-positive advanced breast cancer by PIM1 expression

Conclusions

Real-world data shows PIM1 correlates with high-risk phenotype in HR+ ABC. In contrast to the data reported in RCC, no CDK4/6i showed improved TOT among patients with Q4 PIM1, and other real-world variables may TOT limit analysis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Graff: Financial Interests, Personal, Advisory Board: Pfizer, Seagen, Novartis, AstraZeneca, Genentech, Lilly, Gilead Sciences, Daiichi Sankyo, Menarini; Financial Interests, Personal, Invited Speaker: The Academy for Healthcare Learning, DAVA Oncology, MJH Life Sciences, MedIQ, Medical Educator Consortium; Financial Interests, Personal, Writing Engagement: MedPage Today; Financial Interests, Personal, Stocks/Shares: HCA Healthcare. A. Elliott: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences. R. Mahtani: Financial Interests, Personal, Other, Consultant: Agendia, Amgen, Biotheranostics, Daiichi Sankyo, Genentech, Immunomedics, Lilly, Merck, Novartis, Pfizer, Puma, Sanofi, SeaGen; Financial Interests, Personal, Advisory Board, Consultant and served on advisory boards: AstraZeneca; Financial Interests, Personal, Advisory Board, Consultant: Eisai, Stemline. S. Sammons: Financial Interests, Institutional, Research Funding: AstraZeneca, Abbvie, BMS, Eli Lilly, SeaGen, Sermonix; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi, Eli Lilly, Incyclix, Merck, Pfizer, Sea Gen, Sermonix, Novartis. A. Tan: Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals, Stemline Therapeutics, AstraZeneca; Financial Interests, Institutional, Local PI: Genentech/Roche, Merck, Arvinas; Non-Financial Interests, Leadership Role: ASCO Tapur Publications Committee. C. Nabhan: Financial Interests, Personal, Full or part-time Employment: Caris life sciences; Financial Interests, Personal, Stocks/Shares: Caris life sciences. All other authors have declared no conflicts of interest.