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Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130

Date

28 Sep 2019

Session

Proffered Paper - Breast cancer, metastatic

Presenters

Hope Rugo

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

H.S. Rugo1, S. Loi2, S. Adams3, P. Schmid4, A. Schneeweiss5, C.H. Barrios6, H. Iwata7, V.C. Dieras8, E.P. Winer9, M. Kockx10, D. Peeters11, S.Y. Chui12, J.C. Lin12, A. Nguyen Duc12, G. Viale13, L. Molinero12, L.A. Emens14

Author affiliations

  • 1 Breast Department, University of California San Francisco Comprehensive Cancer Center, 94115 - San Francisco/US
  • 2 Translational Breast Cancer Genomics Lab, Division Of Research, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
  • 3 Medicine, NYU Langone Medical Center, 10016 - New York City/US
  • 4 Centre Of Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University London, EC1M 6BQ - London/GB
  • 5 National Center For Tumor Disease, University Hospital and German Cancer Research Center Heidelberg, 69115 - Heidelberg/DE
  • 6 School Of Medicine, Centro de Pesquisa Clínica, HSL, PUCRS, 90619-900 - Porto Alegre/BR
  • 7 Breast Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 8 Department Of Medical Oncology, Centre Eugène Marquis, 35042 - Rennes/FR
  • 9 Division Of Breast Oncology, Dana-Farber Cancer Institute, 02115 - Boston/US
  • 10 Breast Pathology, HistoGeneX NV, Antwerp/BE
  • 11 Breast Pathology, HistoGeneX NV, 2650 - Antwerp/BE
  • 12 Product Development Oncology, Genentech, Inc,, 94080 - South San Francisco/US
  • 13 Department Of Oncology And Hemato-oncology, University of Milan, European Institute of Oncology IRCCS, 20141 - Milan/IT
  • 14 Medicine/hematology-oncology, University of Pittsburgh Medical Center Hillman Cancer Center, 15232 - Pittsburgh/US
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Background

IMpassion130 is a Ph 3 study evaluating atezolizumab (A) + nab-paclitaxel (nP) vs placebo (P) + nP as 1L treatment for patients (pts) with mTNBC. A+nP significantly improved PFS in PD-L1+ pts (PD-L1 positivity defined as PD-L1–stained immune cells [IC] ≥ 1% of the tumour area by VENTANA PD-L1 SP142 assay). PD-L1+ pts also had clinically meaningful OS benefit with A+nP (25 vs 18 mo; HR 0.71 [95% CI: 0.54, 0.93]; median follow-up, 18 mo; Schmid, ASCO 2019). In this exploratory post-hoc analysis, we evaluated the analytical concordance of SP142 with 2 other PD-L1 IHC assays, and their ability to predict clinical activity.

Methods

Available samples from IMpassion130 were evaluated for PD-L1 status using VENTANA SP142 or SP263 IHC assay (IC ≥ 1%, SP142+ or SP263+) or Dako PD-L1 IHC 22C3 assay (combined proportion score [CPS] ≥ 1, 22C3+) by central laboratory in a biomarker-evaluable population (BEP).

Results

A BEP of 614 pts (68% of ITT) was evaluable for PD-L1 status using the 3 assays. PD-L1+ prevalence was 46% for SP142+, 81% for 22C3+, and 75% for SP263+. The overall percentage agreement (OPA) of SP142 with 22C3 and SP263 was 69% and 63%, respectively. PPAs of 98% for both assays suggest that SP142+ pts are captured by the other two tests, while NPAs were < 45%. The PFS HR (95% CI) was 0.60 (0.47, 0.78) in SP142+ pts, 0.68 (0.56, 0.82) in 22C3+ pts, and 0.64 (0.53, 0.79) in SP263+ pts. The OS HR (95% CI) was 0.74 (0.54, 1.01) in SP142+ pts, 0.78 (0.62, 0.99) in 22C3+ pts, and 0.75 (0.59, 0.96) in SP263+ pts. Subgroup outcomes of SP142+ and SP263+ or 22C3+ indicate that the PFS and OS benefit with A+nP in SP263+/SP142– or 22C3+/SP142– subgroups was smaller than in double-positive subgroups (table).Table:

LBA20

HR (95% CI)SP142
IC < 1%IC ≥ 1%
22C3CPS < 1n = 111 (18%)n = 6 (1%)PPA 98% NPA 45% OPA 69%
PFS 1.00 (0.66, 1.51)
OS 1.08 (0.67, 1.76)
CPS ≥ 1n = 218 (36%)n = 279 (45%)
PFS 0.81 (0.61, 1.09)PFS 0.60 (0.46, 0.78)
OS 0.92 (0.64, 1.31)OS 0.71 (0.52, 0.98)
SP263IC < 1%n = 147 (24%)n = 7 (1%)PPA 98% NPA 34% OPA 64%
PFS 1.13 (0.79, 1.61)
OS 1.1 (0.72, 1.68)
IC ≥ 1%n = 182 (30%)n = 278 (45%)
PFS 0.68 (0.49, 0.94)PFS 0.61 (0.47, 0.79)
OS 0.87 (0.58, 1.29)OS 0.71 (0.52, 0.97)

NPA, negative percentage agreement; OPA, overall percentage agreement; PPA, positive percentage agreement.

Conclusions

At the evaluated cutoffs, 22C3 and SP263 assays identified more pts with PD-L1+ tumours. The pts in the SP142 PD-L1+ population, which is nested within the 22C3 and SP263 PD-L1+ populations, derived the greatest clinical benefit with A+nP.

Clinical trial identification

NCT02425891.

Editorial acknowledgement

Medical writing assistance was provided by Steffen Biechele, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

H.S. Rugo: Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck; Research grant / Funding (institution): OBI; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: MacroGenics; Travel / Accommodation / Expenses: PUMA; Travel / Accommodation / Expenses: Mylan; Research grant / Funding (self): Immunomedics; Research grant / Funding (self), Travel / Accommodation / Expenses: Daiichi Sankyo; Honoraria (self): Celltrion. S. Loi: Research grant / Funding (institution), Non-remunerated activity/ies, Non-remunerated consultant: Novartis; Research grant / Funding (institution), Non-remunerated activity/ies, Non-remunerated consultant: BMS; Research grant / Funding (institution), Non-remunerated activity/ies, Non-remunerated consultant: Roche/Genentech; Research grant / Funding (institution), Non-remunerated activity/ies, Non-remunerated consultant: Merck; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Eli Lilly; Non-remunerated activity/ies, Non-remunerated consultant: Seattle Genetics; Non-remunerated activity/ies, Non-remunerated consultant: Pfizer; Advisory / Consultancy: Aduro Biotechnology. S. Adams: Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Celgene. P. Schmid: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Oncogenex; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Astellas; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Puma biotechnology. A. Schneeweiss: Honoraria (self), Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partners; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses: Pfizer. C.H. Barrios: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Mylan; Research grant / Funding (institution): Merrimack; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): BioMarin; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Bayer; Advisory / Consultancy: Eisai. H. Iwata: Honoraria (self), Advisory / Consultancy: Chugai; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. V.C. Dieras: Honoraria (self): Roche/Genentech; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self): Novartis; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): AbbVie; Honoraria (self): Odonate. E.P. Winer: Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy: Leap; Honoraria (self): Roche/Genentech; Honoraria (self): Infinite MD; Honoraria (self): Carrick Therapeutics; Honoraria (self): GlaxoSmithKline; Honoraria (self): Jounce; Honoraria (self): Genomic Health; Honoraria (self): Merck; Honoraria (self): Seattle Genetics. M. Kockx: Shareholder / Stockholder / Stock options, Full / Part-time employment: HistoGeneX. D. Peeters: Full / Part-time employment: HistoGeneX. S.Y. Chui: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche Ltd.. J.C. Lin: Full / Part-time employment: F. Hoffmann-La Roche Ltd.. A. Nguyen Duc: Full / Part-time employment: F. Hoffmann-La Roche Ltd.. G. Viale: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche/Genentech. L. Molinero: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche Ltd.. L.A. Emens: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self): Celgene; Advisory / Consultancy, Non-remunerated activity/ies, Non-remunerated consulting/advisory board: eTHeRNA; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self): Gritstone; Honoraria (self): MedImmune; Honoraria (self): Molecuvax; Honoraria (self), Travel / Accommodation / Expenses: Macrogenics; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self): Peregrine; Honoraria (self), Travel / Accommodation / Expenses: Replimune; Honoraria (self): Syndax; Honoraria (self), Travel / Accommodation / Expenses: Vaccinex; Research grant / Funding (institution), Licensing / Royalties: Aduro Biotech; Research grant / Funding (institution): Breast Cancer Research Foundation; Research grant / Funding (institution): Corvus.

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