Abstract 127P
Background
In IMpassion050 (NCT03726879), adding atezolizumab (A) to neoadjuvant chemotherapy (CT) and pertuzumab–trastuzumab (PH) did not increase pathological complete response (pCR) vs placebo (Pl), CT and PH in patients (pts) with high-risk, HER2-positive (+) early breast cancer (EBC) in either the intention-to-treat or PD-L1+ populations. Additional BM data are warranted to better inform future immunotherapeutic strategies in HER2+ BC. We report exploratory analyses of the relationship between BMs with pCR, and their dynamics.
Methods
Overall, 454 pts with centrally confirmed HER2+, node+ EBC were randomly assigned to 8 cycles of A and CT with 4 cycles of PH, followed by A plus PH until completion of 1 year of treatment after surgery, or Pl, CT and PH followed by Pl plus PH. Pre-specified HER2, hormone receptor (HR), PD-L1 and PIK3CA mutation status, and tumour-infiltrating lymphocyte (TIL) count were available at baseline; PD-L1 and TILs were available at surgery for pts with residual disease. Rate difference by BM for pCR between arms with 95% confidence intervals (CIs) was calculated using binomial distribution. Predictive factors for pCR were evaluated by calculating the odds ratio (OR) with 95% CI and selecting those with p<0.15 for multivariate analysis.
Results
BM characteristics were well balanced between arms: 89% of tumours were HER2 immunohistochemistry (IHC) 3+; 51%, HR+ (capping at 50%); 48%, PD-L1+; 28%, PIK3CA-mutated; and 37% had a high stromal TIL count (>10%: enriched in the PD-L1+ vs -negative population [56% vs 19%]). No differential treatment effect according to BM subgroup was observed between arms. Association of parameters and pCR are shown in the table. Dynamics of TILs and PD-L1 status will be presented.
Table: 127P
| OR | 95% CI | p-value | |
| N=411 | |||
| Treatment effect (reference: Pl arm) | |||
| A arm | 1.00 | 0.65, 1.54 | 0.9972 |
| HER2 IHC 2+/3+ staining pattern (reference: focal/heterogeneous) | |||
| Homogeneous (≥80% staining) | 2.51 | 1.46, 4.31 | 0.0009 |
| HER2 ISH gene ratio (reference: ≥2 to <4) | |||
| ≥4 | 1.94 | 1.18, 3.20 | 0.0091 |
| HR status (reference: oestrogen and/or progesterone receptor+) | |||
| Oestrogen and progesterone receptor-negative | 2.41 | 1.55, 3.76 | 0.0001 |
| PD-L1 status (reference: tumour-infiltrating immune cells [IC] 0) | |||
| IC 1/2/3 | 1.61 | 1.04, 2.49 | 0.0321 |
| PIK3CA status (reference: mutated) | |||
| No mutation detected | 1.72 | 1.07, 2.77 | 0.0264 |
Conclusions
There was no differential treatment effect detected with the addition of A to CT and PH according to BMs analysed. HER2 IHC staining pattern, gene ratio, and HR, PD-L1 and PIK3CA status were predictive of pCR, in line with prior data.
Clinical trial identification
NCT03726879.
Editorial acknowledgement
Support for third-party editing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
H.A. Zhang: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Funding, Research funding: Roche. C. Lambertini: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. D. Eiger: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. C.H. Barrios: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: MedSIR, Tummi; Financial Interests, Personal, Other, Honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, Eisai, MSD, Lilly, Bayer, AstraZeneca, Zodiac Pharma; Financial Interests, Personal, Other, Travel, accommodations, expenses: Roche/Genentech, Novartis, Pfizer, BMS Brazil, AstraZeneca, MSD Oncology, Lilly; Financial Interests, Institutional, Funding, Research funding: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, Biomarin, Bristol Myers Squibb, Daiichi Sankyo, Abraxis BioScience, AB Science, Asana Biosciences, Medivation, Exelixis, ImClone Systems, LEO Pharma, Millennium, Janssen, Clinica Atlantis, INC Research, Halozyme, Covance, Celgene, inVentiv Health, Shanghai Henlius Biotech, Polyphor, PharmaMar; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Libbs, MSD Oncology, United Medical, Lilly. N. Niikura: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Honoraria: Chugai Pharma, AstraZeneca, Eisai, Novartis, Daiichi Sankyo/UCB Japan, Eli Lilly Japan, MSD, Pfizer Japan, Taiho Pharmaceutical, Kyowa Kirin; Financial Interests, Personal, Funding, Research funding: Chugai Pharma, Nihon Medi-Physics, Daiichi Sankyo, Eisai, Pfizer, Nippon Kayaku, Kyowa Kirin, Takeda, Eli Lilly Japan, Taiho Pharmaceutical, Boehringer Ingelheim, Puma Biotechnology, Mochida Pharmaceutical Co. Ltd. M. Jarzab: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Pfizer; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Lilly, Roche; Financial Interests, Personal, Speaker’s Bureau: Exact Sciences, Roche, Novartis, Pfizer; Financial Interests, Personal, Funding, Research funding: Roche; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer, Lilly, Roche, Novartis. Y. Chang: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Funding, Research funding: Roche. S.L. Huggins-Puhalla: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Advisory Role: AbbVie, Roche/Genentech; Financial Interests, Institutional, Funding, Research funding: AbbVie, Pfizer, AstraZeneca. M. Curran: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. S. Sarkar: Financial Interests, Personal, Full or part-time Employment, Employee: Parexel (F. Hoffmann-La Roche Ltd. external business partner).: Parexel; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. E. Restuccia: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. J. Huober: Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.; Financial Interests, Institutional, Research Grant: Novartis, Lilly; Financial Interests, Personal, Other, Consulting fees: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, AbbVie, Daiichi, Gilead; Financial Interests, Personal, Other, Honoraria: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Eisai, AbbVie, Seagen, Gilead, Daiichi; Financial Interests, Personal, Other, Travel: Roche, Pfizer, Novartis, Celgene, Daiichi, Gilead.