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)

Date

28 Sep 2019

Session

Proffered Paper - Breast cancer, metastatic

Presenters

Leisha Emens

Citation

Annals of Oncology (2019) 30 (suppl_5): v104-v142. 10.1093/annonc/mdz242

Authors

L.A. Emens1, F.J. Esteva2, M. Beresford3, C. Saura4, M. De Laurentiis5, S. Kim6, S. Im7, Y. Wang8, A. Mani9, J. Shah9, H. Liu9, S. de Haas10, M. Patre11, S. Loi12

Author affiliations

  • 1 Medicine/hematology-oncology, UPMC Hillman Cancer Center, 15232 - Pittsburgh/US
  • 2 Medical Oncology, Perlmutter Cancer Center at NYU Langone Medical Center, 10016 - New York/US
  • 3 Oncology And Haematology, Royal United Hospitals Bath NHS Foundation Trust, BA1 3NG - Bath/GB
  • 4 Medicine And Surgery, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 5 Surgical Oncology, IRCCS Istituto Nazionale Tumori Fondazione Pascale, 80131 - Naples/IT
  • 6 Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-931 - Seoul/KR
  • 7 Internal Medicine, SNUH-Seoul National University Hospital, 03080 - Seoul/KR
  • 8 Product Development, Roche (China) Holding Ltd, 201203 - Shanghai/CN
  • 9 Product Development Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 10 Oncology Biomarker Development, F. Hoffmann-La Roche, 4051 - Basel/CH
  • 11 Product Development Oncology, F. Hoffmann-La Roche, 4051 - Basel/CH
  • 12 Translational Breast Cancer Genomics Lab, Division Of Research, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
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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

ITT 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 OSNENENENENENE
Stratified 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 <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.

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