Breast Cancer (ABC) comprises both locally advanced breast cancer (LABC) and metastatic breast cancer (MBC) [1]. Although treatable, MBC remains virtually an incurable disease with a median overall survival (OS) of $3 years and a 5-year survival of only $25% [2, 3]. The MBC Decade Report [2] shows that progress has been slow in terms of improved outcomes, quality of life (QoL), awareness and information regarding ABC. More recently, some studies seem to indicate an improvement in OS, mostly due to advances in human epidermal growth factor receptor 2 (HER2)-positive ABC [4][5][6]. The better survival is seen in an environment with access to the best available care and particularly in de novo ABC, while recurrent ABC seems to become harder to manage [7,8].The last decade has seen an improvement in the levels of evidence (LoEs) used for many of the ABC recommendations, however, still far from the LoEs existing for the majority of early

Background: In the phase 3 IMpassion130 trial, combining atezo with first-line nabpaclitaxel for mTNBC showed significantly improved progression-free survival (PFS) and clinically meaningful overall survival (OS) benefit in patients with PD-L1+ mTNBC [Schmid NEJM 2018]. IMpassion131 (NCT03125902) evaluated atezo + PAC as firstline treatment for mTNBC. a Unconfirmed abstracts Annals of Oncology Volume 31 -Issue S4 -2020 S1147

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Background: The Phase III IMpassion130 study (NCT02425891) evaluated atezolizumab (anti–PD-L1) + nab-paclitaxel (nabPx) vs placebo + nabPx as first-line treatment for pts with metastatic triple-negative breast cancer (TNBC). The study met its co-primary PFS endpoint in ITT pts and in pts with PD-L1 ≥1% on tumor-infiltrating immune cells (IC+). Clinically meaningful OS benefit was seen at interim OS analysis, notably in pts with PD-L1 IC+ tumors (Table). Here we report exploratory efficacy data in immunologically and clinically relevant, biomarker-defined subgroups. Methods: Pts had histologically documented metastatic or unresectable locally advanced TNBC (evaluated locally per ASCO-CAP). Pts were randomized 1:1 to nabPx 100 mg/m2 IV (d1, 8 and 15 of a 28-d cycle) + atezolizumab 840 mg IV q2w or placebo (A-nabPx or P-nabPx) until progression or toxicity. Exploratory biomarkers were centrally analyzed: PD-L1 on tumor cells (TC) by VENTANA SP142 IHC assay, intratumoral CD8 by IHC, stromal tumor-infiltrating lymphocytes (sTILs), BRCA1/2 mutational status and ER/PR/HER2 status. Results: PD-L1 IC was highly predictive of A-nabPx efficacy (Table). The majority of PD-L1 TC+ tumors were also PD-L1 IC+. Intratumoral CD8, but not sTILs, were well correlated with PD-L1 IC. Consequently, CD8 was predictive of A-nabPx efficacy for PFS/OS, while sTILs only predicted PFS benefit. Local vs central TNBC assessment was concordant in most pts. Local vs central lab–defined TNBC populations derived similar benefit from A-nabPx. Efficacy by BRCA status will be presented to evaluate the benefits of immunotherapy for this subgroup. Conclusions: Exploratory efficacy analyses from IMpassion130 suggest consistency between local and central ER/PR/HER2 testing and that PD-L1 IC is the most robust predictive biomarker for selecting untreated mTNBC pts who benefit from A-nabPx. PopulationA-nabPxP-nabPxPrimary data, stratifiedITT, n451451mPFS (95% CI), mo7.2 (5.6-7.5)5.5 (5.3-5.6)PFS HR (95% CI)0.80 (0.69-0.92); P=0.0025mOS (95% CI), mo21.3 (17.3-23.4)17.6 (15.9-20.0)OS HR (95% CI)0.84 (0.69-1.02); P=0.0840PD-L1 IC+, n (%)185 (41%)184 (41%)mPFS (95% CI), mo7.5 (6.7-9.2)5.0 (3.8-5.6)PFS HR (95% CI)0.62 (0.49-0.78); P<0.0001mOS (95% CI) mo25.0 (22.6-NE)15.5 (13.1-19.4)OS HR (95% CI)0.62 (0.45-0.86)aExploratory/biomarker data, unstratifiedPD-L1 TC evaluable, n449451PD-L1 TC+, n (%)38 (8%)40 (9%)PFS HR (95% CI)0.51 (0.31-0.84)OS HR (95% CI)0.63 (0.33-1.21)CD8 evaluable, n371349CD8 ≥0.5%, n (%)261 (70%)239 (68%)PFS HR (95% CI)0.74 (0.61-0.91)OS HR (95% CI)0.66 (0.50-0.88)sTIL evaluable, n448444sTIL ≥10%, n (%)147 (33%)137 (31%)PFS HR (95% CI)0.66 (0.50-0.86)OS HR (95% CI)0.75 (0.51-1.10)cTNBC evaluable, n420412cTNBC ITT, n (%)307 (73%)317 (77%)PFS HR (95% CI)0.81 (0.68-0.98)OS HR (95% CI)0.85 (0.67-1.08)cTNBC PD-L1 IC+, n (%)133 (43%)134 (42%)PFS HR (95% CI)0.67 (0.51-0.88)OS HR (95% CI)0.69 (0.47-1.00)Data cutoff: 17 April 2018 (12.9-mo median follow up).cTNBC, centrally confirmed TNBCTC/IC+, PD-L1 ≥1% (VENTANA SP142 assay)a Not formally tested per hierarchical study design. Citation Format: Emens LA, Loi S, Rugo HS, Schneeweiss A, Diéras V, Iwata H, Barrios CH, Nechaeva M, Molinero L, Nguyen Duc A, Funke R, Chui SY, Husain A, Winer EP, Adams S, Schmid P. IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-04.

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