2609 - Overall survival (OS) in KATE2, a phase 2 study of programmed death ligand 1 (PD-L1) inhibitor atezolizumab (atezo)+trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC)

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 1200 mg or pbo, + T-DM1 3.6 mg/kg IV q3w. Pts were grouped by tumor infiltrating PD-L1+ immune cell (IC) status: IC0 vs IC1/2/3 (<1% vs ≥ 1%, respectively) using VENTANA SP142. The preplanned OS analysis in the ITT population was a secondary endpoint with 30% power to detect an effect. OS in PD-L1 subgroups was analyzed post-hoc.

Results

As of the cutoff date (11 Dec 2018), median follow-up was 19.5 mo in the atezo+T-DM1 arm and 18.2 mo 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.Table:

305O

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 <25k: Aduro. F.J. Esteva: Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis. C. Saura: Research grant / Funding (institution): Roche-Genentech; Research grant / Funding (institution): Macrogenics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Piqur therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Puma biotechnology; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Synthon biopharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Genomyc Health; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. M. De Laurentiis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. S. Kim: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sanofi-Genzyme; Research grant / Funding (institution): Dongkook Inc. S. Im: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Roche; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Novartis. Y. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche (China) Holding Ltd. A. Mani: Full / Part-time employment: Roche/Genentech; Shareholder / Stockholder / Stock options: Roche/Genentech. J. Shah: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. H. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. S. de Haas: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. M. Patre: Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment, Methods of treating her2 - positive metastatic breast cancer A61K47/6855: F. Hoffman-La Roche. S. Loi: Research grant / Funding (institution), Non-remunerated activity/ies: Novartis; Research grant / Funding (institution), Non-remunerated activity/ies: Bristol Meyers Squibb; Research grant / Funding (institution), Non-remunerated activity/ies: Roche-Genentech; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution), Non-remunerated activity/ies: Pfizer; Non-remunerated activity/ies: Seattle Genentics; Non-remunerated activity/ies: Merck; Research grant / Funding (institution): Eli Lilly. All other authors have declared no conflicts of interest.