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Clinical Trial
. 2024 Mar 9;15(1):2153.
doi: 10.1038/s41467-024-45591-7.

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial

Liang Huang  1   2 , Da Pang  3 , Hongjian Yang  4 , Wei Li  5 , Shusen Wang  6 , Shude Cui  7 , Ning Liao  8 , Yongsheng Wang  9 , Chuan Wang  10 , Yuan-Ching Chang  11 , Hwei-Chung Wang  12 , Seok Yun Kang  13 , Jae Hong Seo  14 , Kunwei Shen  15 , Suphawat Laohawiriyakamol  16 , Zefei Jiang  17 , Haiyan Wang  18 , François Lamour  19   20 , Grace Song  21 , Michelle Curran  19 , Chunzhe Duan  22 , Sanne Lysbet de Haas  19 , Eleonora Restuccia  19 , Zhimin Shao  23   24
Affiliations
Clinical Trial

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial

Liang Huang et al. Nat Commun. .

Abstract

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

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Conflict of interest statement

All authors report receiving research support in the form of third-party writing assistance for this manuscript, provided by F. Hoffmann-La Roche Ltd. L.H., D.P., H.Y., W.L., S.W., S.C., N.L., Y.W., C.W., Y-C.C., H-C.W., S.Y.K., J.H.S., K.S., Z.J., and Z.S. report contracted research from F. Hoffmann-La Roche Ltd. S.L. reports contracted research from F. Hoffmann-La Roche Ltd/Genentech, Inc. via Roche Thailand Ltd. S.W. reports honoraria from F. Hoffmann-La Roche Ltd. H.W., C.D., S.L.dH., and E.R. report ownership interest (stocks, stock options, patent or other intellectual property or other ownership interest excluding diversified mutual funds) in F. Hoffmann-La Roche Ltd. F.L., M.C., S.L.dH., and E.R. report employment with F. Hoffmann-La Roche Ltd. H.W. reports employment with Roche Product Development. C.D. reports employment with Roche (China) Holding Ltd. G.S. reports employment with Hangzhou Tigermed Consulting Co., Ltd.

Figures

Fig. 1
Fig. 1. CONSORT diagram.
FEC 5-fluorouracil, epirubicin, and cyclophosphamide. HER2 human epidermal growth factor receptor 2, tpCR total pathologic complete response.
Fig. 2
Fig. 2. Kaplan–Meier plots of the long-term efficacy endpoints EFS and DFS.
a EFS in the ITT population and b DFS in all patients who underwent surgery. 95% CIs and p values (two-sided) for differences in event rates were from z-tests using the standard errors for the Kaplan–Meier estimates. CI confidence interval, DFS disease-free survival, EFS event-free survival, HR hazard ratio, ITT intention-to-treat.
Fig. 3
Fig. 3. Kaplan–Meier plot of DFS according to tpCR in the ITT population with both treatment arms combined.
CI confidence interval, DFS disease-free survival, ITT intention-to-treat, tpCR total pathologic complete response.
Fig. 4
Fig. 4. Subgroup analysis of DFS in the tpCR population.
CI confidence interval, DFS disease-free survival, tpCR total pathologic complete response.
Fig. 5
Fig. 5. Subgroup analysis of DFS in the population with residual invasive disease.
CI confidence interval, DFS disease-free survival.
Fig. 6
Fig. 6. Biomarker subgroup analysis of tpCR rates in the ITT population.
Boxes represent sample sizes and odds ratios; whiskers represent 95% CI; the vertical dotted line represents the odds ratio for all patients. CI confidence interval, HER2 human epidermal growth factor receptor 2, IHC immunohistochemistry, ITT intention-to-treat; mRNA, messenger RNA, PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PTEN phosphatase and tensin homolog, tpCR total pathologic complete response.
See this image and copyright information in PMC

References

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