6571 - Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130

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

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.