Abstract GS1-04: Correlative biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA Phase III studies

Autor: Anwesha Chaudhury, Nuria Chic, Tetiana Taran, D. Martinez, Nadia Solovieff, Karen Rodriguez-Lorenc, Fara Brasó-Maristany, Aleix Prat, Faye Su, Laia Paré, Olga Martínez, Naveen Babbar
Rok vydání: 2021
Předmět:
Zdroj: Cancer Research. 81:GS1-04
ISSN: 1538-7445
0008-5472
Popis: Background: The prognostic and predictive value of the 4 main intrinsic subtypes of breast cancer (ie, luminal A [LumA], luminal B [LumB], human epidermal growth factor receptor 2 enriched [HER2E], and basal-like) in hormone receptor-positive, HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) and ribociclib (RIB) is currently unknown. The MONALEESA-2, -3, and -7 trials all showed a significant benefit in progression-free survival (PFS) with RIB over placebo (PBO; Hortobagyi et al. Ann Oncol. 2018; Slamon et al. J Clin Oncol. 2018; Tripathy et al. Lancet Oncol. 2018). Here, we correlate ABC intrinsic subtypes with the PFS benefit of RIB in the MONALEESA trials. Methods: Patient samples from the MONALEESA-2, -3, and -7 trials underwent PAM50-based subtyping (blinded from clinical data), and the correlation between intrinsic subtype and PFS was analyzed. Gene expression profiling of formalin-fixed, paraffin-embedded tumor samples was performed using a customized NanoString nCounter GX 800-gene panel. The prognostic and/or predictive relationship of PAM50-based subtypes with PFS and the risk of tumor progression by subtype were evaluated using univariate and multivariable Cox proportional hazards models. Multivariable models were adjusted for known clinical prognostic factors, including age, prior chemotherapy, prior ET, ECOG performance status, visceral disease (presence of liver/lung metastases), bone-only metastases, histological grade, number of metastatic sites, and de novo metastatic disease. Results: A total of 1160 tumor samples from both the RIB (n = 672) and PBO (n = 488) treatment arms of the MONALEESA trials were profiled. Subtype distribution was generally consistent across treatment arms (Table). The associations between intrinsic subtypes and PFS were statistically significant in both treatment arms (P < .0001). Compared with patients with LumA subtype, which is the subtype that is the most prevalent and has the best prognostic outcome, patients with LumB, HER2E, and basal-like subtypes had a 1.41, 2.30, and 3.97 times higher risk of tumor progression, respectively, after adjusting for other clinical-pathologic variables and treatment arm. In terms of treatment benefit, all subtypes except for basal-like showed a significant PFS benefit with RIB treatment (Table). Patients with HER2E (hazard ratio [HR], 0.389; P < .0001), LumB (HR, 0.521; P = .0001), LumA (HR, 0.633; P = .0007), and normal-like (HR, 0.467; P = .0005) subtypes all derived benefit from RIB treatment, with HER2E demonstrating the greatest benefit. Patients with the basal-like subtype (n = 30) did not derive benefit from RIB (HR, 1.15; P = .767), although these results should be interpreted with caution due to the small sample size (RIB: 2%; PBO: 3%). Conclusions: This is the largest analysis evaluating the correlation of intrinsic ABC subtype with efficacy outcomes in patients treated with CDK4/6 inhibitors. Patients with HER2E, LumA, LumB, and normal-like subtypes all exhibited a consistent PFS benefit with RIB treatment, while patients with basal-like ABC (RIB: 2%; PBO: 3%) did not. The HER2E subtype (RIB: 14%; PBO: 11%) exhibited the greatest relative reduction in risk of progression or death (61%) with RIB plus ET. Table.SubtypeTreatment ArmDistribution, n (%)Median PFS, months, (95% CI)HRP ValueLuminal ARIB320 (48)29.60 (23.03-NA)0.63.0007PBO222 (45)19.48 (15.61-24.80)Luminal BRIB154 (23)22.21 (18.79-NA)0.52< .0001PBO124 (25)12.85 (10.98414.82)HER2-enrichedRIB95 (14)16.39 (12.71-24.6)0.39< .0001PBO52 (11)5.52 (3.12-9.17)BasalRIB16 (2)3.71 (1.91-13)1.15.77PBO14 (3)3.58 (1.87-NA)NormalRIB87 (13)22.34 (16.56-NA)0.47.0005PBO76 (16)11.10 (7.39-16.56)NA, not achieved. Citation Format: Aleix Prat, Anwesha Chaudhury, Nadia Solovieff, Laia Paré, Debora Martinez, Nuria Chic, Olga Martínez, Fara Brasó-Maristany, Karen Rodriguez-Lorenc, Tetiana Taran, Naveen Babbar, Faye Su. Correlative biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA Phase III studies [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS1-04.
Databáze: OpenAIRE
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