LAUSR

Abstract Background T-DM1 is indicated for the treatment of HER2+ metastatic BC previously treated with trastuzumab and a taxane, separately or in combination. Atezo is an anti-PD-L1 antibody that inhibits PD-L1 binding to PD-1 and B7.1 thereby restoring antitumor immunity. In a phase 3 study, the addition of atezo to nab-paclitaxel significantly improved PFS in PD-L1+ pts with metastatic triple negative BC. In KATE2 (NCT02924883), adding atezo to T-DM1 in pts with HER2+ BC did not significantly increase PFS compared to T-DM1+pbo in the ITT population, but PFS was numerically longer in PD-L1+ pts. Here, we present OS and updated safety data from KATE2. Methods Pts with advanced HER2-positive BC that had progressed after treatment with trastuzumab and a taxane were randomized 2:1 to atezo 1200mg or pbo, + T-DM1 3.6mg/kg IV q3w. Pts were grouped by tumor infiltrating PD-L1+ immune cell (IC) status: IC0 vs IC1/2/3 ( Results As of the cutoff date (11 Dec 2018), median follow-up was 19.5mo in the atezo+T-DM1 arm and 18.2mo in the pbo+T-DM1 arm. With 52 OS events reported, median OS was not reached in either arm. In the ITT population, 1-year OS was similar in both arms. In the PD-L1+ subgroup, 1-year OS was greater in the atezo+T-DM1 arm. The safety profile was consistent with the known safety profile of each drug. Grade ≥3 AEs (52.6% vs 44.8%) and serious AEs (36.1% vs 20.9%)—primarily pyrexia—were more frequent in the atezo+T-DM1 arm than in the T-DM1+pbo arm. Conclusions These data suggest a possible OS benefit with atezo+T-DM1 in PD-L1+ pts. However, given the small number of OS events, the short follow-up and lack of statistical power, further study is necessary.Table305OTableITT PopulationPD-L1+ SubgroupPD-L1- Subgroup(IC 1/2/3)(IC 0)Atezo +Pbo +Atezo +Pbo +Atezo +Pbo +T-DM1T-DM1T-DM1T-DM1T-DM1T-DM1(n=133)(n=69)(n=57)(n=27)(n=76)(n=42)Pts with OS event, n (%)32201182112(24.1%)(29.0%)(19.3%)(29.6%)(27.6%)(28.6%)Median OSNENENENENENEStratified HR (95% CI)0.740.550.88(0.42–1.30)(0.22–1.38)(0.43–1.80)1-year survival rate89.1%89.0%94.3%87.9%85.1%89.7%CI, confidence interval; HR, hazard ratio; IC, immune cell infiltrate staining of PD-L1; NE, not estimable; OS, overall survival. Clinical trial identification NCT02924883. Editorial acknowledgement Medical writing assistance was provided by Katherine Stevens-Favorite, PhD and Holly Strausbaugh, PhD of Twist Medical LCC and funded by F. Hoffmann-La Roche. Legal entity responsible for the study F. Hoffmann - La Roche. Funding F. Hoffmann - La Roche. Disclosure L.A. Emens: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyers Squibb; Honoraria (self), Advisory / Consultancy: Celgene; Advisory / Consultancy: eTHeRNA; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Gristone; Honoraria (self), Advisory / Consultancy: Medimmune; Advisory / Consultancy: Molecuvax; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Macrogenics; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Peregrine; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Replimune; Honoraria (self), Advisory / Consultancy: Syndax; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Vaccinex; Research grant / Funding (institution): Aduro; Research grant / Funding (institution), Same dislosure for Corvus, Dept of Defense, EMD Serono, HeritX Inc, Maxcyte, Merck: Breast Cancer Research Foundation; Research grant / Funding (institution), Licensing / Royalties, IND Licensing vaccine