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Clinical Trial
. 2025 Sep 11;32(9):e240353.
doi: 10.1530/ERC-24-0353. Print 2025 Sep 1.

Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer

Takayuki Ueno  1 , Louis W C Chow  2 , Wonshik Han  3 , Chiun Sheng Huang  4 , G Bruce Mann  5 , Satoshi Morita  6 , Hironori Haga  7 , Elham Fakhrejahani  8 , Takayuki Kobayashi  9 , Hiroko Bando  10 , Kenichi Inoue  11 , Mariko Tokiwa  12 , Hirofumi Suwa  13 , Tomoyuki Aruga  14 , Sachiko Minamiguchi  7 , Yosuke Yamada  7 , Yuko Tanabe  15 , Masahiro Takada  16 , Toshinari Yamashita  17 , Hiroji Iwata  18 , Chi-Feng Chung  19 , Sachiko Takahara  20 , Eriko Tokunaga  21 , Shigeru Imoto  22 , Eun Sook Lee  23 , Yasuaki Sagara  24 , Jee Hyun Kim  25 , Richard H DeBoer  26 , Hyun-Ah Kim  27 , Hung Wen Lai  28 , Ming Feng Hou  29 , Michelle White  30 , Yoshiko Umeyama  31 , Masakazu Toi  8
Affiliations
Clinical Trial

Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer

Takayuki Ueno et al. Endocr Relat Cancer. .

Abstract

The addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor to endocrine therapy augments biological response in breast cancer. This phase III randomized, double-blind study evaluated the efficacy of adding palbociclib to neoadjuvant endocrine therapy (NET) for operable, hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Patients randomly received 16 weeks of endocrine therapy (letrozole for postmenopausal and tamoxifen plus ovarian function suppression for pre-/perimenopausal patients) plus palbociclib or placebo. The co-primary endpoints included preoperative endocrine prognostic index (PEPI) score and EndoPredict (EPclin) risk score according to the gatekeeping procedure. Of 141 randomized patients, 130 completed the treatment with surgical samples evaluable for endpoints in 126 patients. The proportion of patients with a low, moderate, and high PEPI score was 15.2, 50.0, and 34.8% in the palbociclib arm and 13.3, 55.0, and 31.7% in the placebo arm, respectively, with no statistical difference (one-sided P = 0.563). Statistical analysis was not performed on EPclin risk score. No new safety signals were reported. Permanent treatment discontinuation by adverse events was reported for seven (9.7%) and zero patients in the palbociclib and placebo arms, respectively. In conclusion, the addition of palbociclib to NET did not improve the efficacy. ClinicalTrials.gov NCT03969121.

Keywords: CDK4/6; breast cancer; neoadjuvant endocrine therapy; palbociclib; pre-operative endocrine prognostic index (PEPI).

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Conflict of interest statement

Takayuki Ueno received lecture fees from Astra Zeneca, Chugai Pharmaceutical, Eisai Co. Ltd and Novartis Pharma KK. Louis W C Chow received funding or grants from Merck & Co Inc, Novartis Pharmaceuticals Corporation, and OBI Pharma Inc. Wonshik Han reports equity and stock ownership of DCGen Inc, and received advisory fees, funding, grants, and lecture fees from Takeda, Shinpoong, Kwangdong, Agendia, Handok, Hanall, Novartis, Celltrion, Hanlim, Genomic Health, Kyowa Kirin, Pfizer, Roche, Alvogen, and Amgen. Chiun Sheng Huang received advisory fees, funding, grants, and lecture fees from AstraZeneca, Daiichi Sankyo, EirGenix, Lilly, MSD, Novartis, OBI Pharma, Pfizer, Roche, Seagen, Gilead Sciences Inc, and Aston Sci. Satoshi Morita received lecture fees from Astellas Pharma Inc, AstraZeneca Kabushiki Kaisha, Bristol Myers Squibb Co, Chugai Pharmaceutical Co Ltd, Eisai Co Ltd, Eli Lilly Japan KK, MSD KK, Novartis Pharma Japan, Ono Pharmaceutical Co Ltd, Pfizer Japan Inc, and Taiho Pharmaceutical Co Ltd. Hiroko Bando received advisory and lecture fees from AstraZeneca, Chugai Pharmaceutical Co Ltd, Daiichi Sankyo Inc, Eisai Co Ltd, Eli Lilly, Kyowa Kirin Inc, Novartis, and Pfizer Japan Inc. Kenichi Inoue received funding and grants from AstraZeneca, Chugai Pharma, Daiichi Sankyo, MSD, Ono, Pfizer, and Takeda. Tomoyuki Aruga received lecture fees from AstraZeneca, Chugai, Eli Lilly, and Pfizer. Yuko Tanabe received funding and grants from Daiichi Sankyo, MSD, and Taiho. Masahiro Takada received lecture fees, funding, and grants from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Lilly, Medbis, Pfizer, and Yakult. Toshinari Yamashita received lecture fees, funding, and grants from Chugai, Daiichi Sankyo, Eisai, Eli Lilly, AstraZeneca, Taiho, Pfizer, MSD, Novartis Pharma, Kyowa Kirin, Gilead Sciences, Ono, Seagen, and Nippon Kayaku. Hiroji Iwata received funding, grants, and advisory and lecture fees from Amgen, AstraZeneca, Chugai, Daiichi Sankyo, Lilly, MSD, Novarti, Pfizer, and Sanofi. Chi-Feng Chung received advisory fees from AstraZeneca, CANbridge Pharma, Daiichi Sankyo, EirGenix, Lotus, and Roche. Eriko Tokunaga received lecture fees from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Kirin, Nihon Kayaku, and Pfizer. Shigeru Imoto received funding and grants from Chugai, Eisai, and Taiho Pharma. Yasuaki Sagara received lecture fees from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Hakko Kirin, MSD, and Pfizer. Jee Hyun Kim received advisory and lecture fees from Bixink, Daiichi Sankyo, Eisai, Everest Medicines, Lilly Korea, Novartis, Ono Pharma Korea Ltd, Pfizer Korea, Roche Diagnostics, Roche Korea, Sanofi-Aventis, and Yuhan. Richard H DeBoer received lecture and advisory fees, funding, and grants from Amgen Australia, AstraZeneca, Eli Lilly, Gilead Australia, MSD, and Pfizer. Michelle White received advisory fees from Pfizer. Yoshiko Umeyama is an employee of Pfizer R&D Japan and holds stock in Pfizer Inc. Masakazu Toi received funding, grants, advisory, and lecture fees from AFI Technologies, Japan Breast Cancer Research Group, Kyoto Breast Cancer Research Network, Astellas, AstraZeneca, Athenex Oncology, Bertis, BMS, Chugai, Daiichi Sankyo, Devicore Medical Japan, Eisai, Eli Lilly, Exact Sciences, GL Sciences, Kansai Medical Net, Luxonus, MSD, Nippon Kayaku, Novartis, Pfizer, Sanwa Shurui, Shimadzu, Shionogi, Taiho, Takeda, Terumo, and Yakult. A part of the findings was presented at San Antonio Breast Cancer Symposium 2022 under the title ‘Neoadjuvant hormonal therapy plus palbociclib versus hormonal therapy plus placebo in women with operable, hormone sensitive and HER2-negative primary breast cancer’ (38).

Figures

Figure 1
Figure 1
Study flow diagram.
See this image and copyright information in PMC

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