Abstract 127P
Background
IMpassion050 (NCT03726879) showed no increase in pathological complete response (pCR; ypT0/is ypN0) rates for neoadjuvant A + PH + CT vs. placebo (pbo) + PH + CT in the intention-to-treat (ITT) or PD-L1+ populations in patients (pts) with high-risk HER2+ eBC. Safety was consistent with that of A in other combination studies. We report descriptive long-term efficacy and safety.
Methods
Pts with a primary tumour >2 cm and histologically confirmed positive lymph node status were randomised 1:1 to A/pbo + PH + CT. After surgery, pts continued A/pbo + PH up to 1 yr. Pts with residual disease could switch to A/pbo + trastuzumab emtansine (T-DM1) for 14 cycles. Secondary endpoints: disease-free survival (DFS; time from surgery to disease recurrence or death); event-free survival (EFS; time from randomisation to disease recurrence, tumour progression or death); safety. Stratification: stage at diagnosis; hormone receptor (HR) status; PD-L1 status.
Results
At data cut-off (24 Aug 2023), 411/454 pts (90.5%) remained on-study (A arm: 206/226; pbo arm: 205/228); median follow-up was 44.2 and 43.4 months, respectively. A median of 14 PH cycles was given in both arms. DFS/EFS, including subgroup analyses, are shown in the table. There were 24 deaths (A arm: 11; pbo arm: 13). In the adjuvant phase (A vs. pbo), more pts had adverse events of special interest (AESIs; 59.4% vs. 47.0%); there were no grade 5 AESIs; and the most common AEs (in ≥10% pts in either arm) were radiation skin injury (24.0% vs. 19.4%), arthralgia (20.7% vs. 17.1%) and diarrhoea (20.7% vs. 13.4%). Table: 127P
| DFS (N = 434 [217 per arm]; pts who had surgery) | EFS (N = 454 [226 A, 228 pbo]; ITT population) | |
| 3-yr event-free rate, % (95% confidence interval [CI]) | A: 92.9 (89.5, 96.4) Pbo: 88.5 (84.1, 92.8) | A: 91.4 (87.7, 95.1)Pbo: 89.0 (84.8, 93.2) |
| Hazard ratio (95% CI) | 0.71 (0.38, 1.32)Unstratified | 0.90 (0.50, 1.59)Stratified |
| Covariates, hazard ratio (95% CI) | ||
| Stage at diagnosis | ||
| T2 | 0.38 (0.13, 1.06) | 0.56 (0.24, 1.34) |
| T3–T4 | 1.13 (0.50, 2.56) | 1.33 (0.60, 2.94) |
| HR status | ||
| + | 0.43 (0.17, 1.13) | 0.57 (0.24, 1.36) |
| – | 1.07 (0.46, 2.53) | 1.28 (0.58, 2.82) |
| PD-L1 status | ||
| + | 1.38 (0.51, 3.69) | 1.67 (0.65, 4.32) |
| – | 0.44 (0.19, 1.02) | 0.58 (0.27, 1.22) |
| pCR status | ||
| Non-pCR | 0.71 (0.31, 1.63) | 0.95 (0.45, 1.98) |
| pCR | 0.66 (0.26, 1.70) | 0.76 (0.30, 1.88) |
Conclusions
Although there was no increase in pCR rates, 3-yr DFS/EFS rates were numerically improved with A in the ITT population, including in pts with PD-L1–negative, HR+ or stage T2 disease. Safety was consistent with the known profiles of PH, T-DM1 and A. These results highlight the value of long-term clinical endpoints when investigating early-stage cancer immunotherapies.
Clinical trial identification
NCT03726879.
Editorial acknowledgement
Support for third-party medical writing assistance for this abstract, furnished by Katie Wilson, PhD, of Nucleus Global, an Inizio company.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
J. Huober: Financial Interests, Personal, Speaker’s Bureau: Roche, Lilly, Pfizer, Celgene, MSD Oncology, AstraZeneca, AbbVie, Novartis, Seagen, Daiichi Sankyo/AstraZeneca, Gilead Sciences and Eisai; Financial Interests, Institutional, Research Grant: Novartis, Celgene and Lilly; Financial Interests, Personal, Research Grant: Hexal and Roche; Financial Interests, Personal, Invited Speaker, Travel, accommodation, expenses: Novartis, Roche, Pfizer, Celgene and Daiichi Sankyo; Non-Financial Interests, Personal, Member: German Breast Group; Financial Interests, Personal, Advisory Role: Novartis, Roche, Pfizer, Lilly, Celgene, AstraZeneca, AbbVie, Eisai, MSD Oncology, Hexal and Daiichi Sankyo/AstraZeneca; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. C.H. Barrios: Financial Interests, Personal, Speaker’s Bureau: Novartis, Roche/Genentech, Pfizer, GSK, Sanofi, Boehringer Ingelheim, Eisai, MSD, Lilly, Bayer, AstraZeneca and Zodiac Pharma; Financial Interests, Personal, Stocks/Shares: MedSIR and Tummi; Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GSK, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, Biomarin, Bristol Myers Squibb, Daiichi Sankyo and 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 and PharmaMar; Financial Interests, Personal, Funding, Travel, accommodation, expenses: Roche/Genentech, Novartis, Pfizer, BMS Brazil, AstraZeneca, MSD Oncology and Lilly; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Roche/Genentech, Novartis, GSK, Eisai, Pfizer, AstraZeneca, Libbs, MSD Oncology, United Medical and Lilly; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. N. Niikura: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma, AstraZeneca, Eisai, Novartis, Daiichi Sankyo/UCB Japan, Nippon Kayaku, Lilly Japan, MSD, Pfizer, Nihon Medi-Physics, Taiho Pharmaceutical, Takeda and Kyowa Kirin; Financial Interests, Institutional, Research Grant: Pfizer, Nippon Kayaku and Lilly Japan; Financial Interests, Personal, Research Grant: Chugai Pharma, Nihon Medi-Physics, Daiichi Sankyo, Eisai, Kyowa Kirin, Takeda and Roche; Financial Interests, Personal, Advisory Role: Roche, Pfizer, AstraZeneca, MSD and Daiichi Sankyo; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. M. Jarzab: Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, Pfizer and Exact Sciences; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Funding, Travel, accommodation, expenses: Pfizer, Lilly, Roche and Novartis; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Lilly and Roche; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. Y. Chang: Financial Interests, Personal, Research Grant: Roche; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. S.L. Huggins-Puhalla: Financial Interests, Institutional, Research Grant: AbbVie, Pfizer and AstraZeneca; Financial Interests, Personal, Advisory Role: AbbVie and Roche/Genentech; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. J.L. Pedrini: Financial Interests, Personal, Research Grant: Roche; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. L. Zhukova: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Novartis and Biocad; Financial Interests, Personal, Research Grant: Roche and AstraZeneca; Financial Interests, Personal, Advisory Role: Biocad; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. M. Curran, V. Craine, C. Lambertini, 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, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. D. Eiger: Financial Interests, Personal, Full or part-time Employment, Previous employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Research Grant: Novartis; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. H. Zhang: Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Advisory Role: Roche/Genentech; Non-Financial Interests, Personal, Other, Research funding in the form of third-party medical writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd.