Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer

被引：139

作者：

Cottu, P. ^{[1
,2
]}

D'Hondt, V. ^{[3
]}

Dureau, S. ^{[4
]}

Lerebours, F. ^{[5
]}

Desmoulins, I. ^{[6
]}

Heudel, P-E ^{[7
]}

Duhoux, F. P. ^{[8
]}

Levy, C. ^{[9
]}

Mouret-Reynier, M-A ^{[10
]}

Dalenc, F. ^{[11
]}

Frenel, J-S ^{[12
]}

Jouannaud, C. ^{[13
]}

Venat-Bouvet, L. ^{[14
]}

Nguyen, S. ^{[15
]}

Ferrero, J-M ^{[16
]}

Canon, J-L ^{[17
]}

Grenier, J. ^{[18
]}

Callens, C. ^{[2
,19
]}

Gentien, D. ^{[2
,20
]}

Lemonnier, J. ^{[21
]}

Vincent-Salomon, A. ^{[2
,22
]}

Delaloge, S. ^{[23
]}

机构：

[1] Inst Curie, Dept Med Oncol, 26 Rue Ulm, F-75005 Paris, France

[2] Paris Sci & Lettres Univ, Paris, France

[3] Inst Reg Canc Montpellier, Dept Med Oncol, Montpellier, France

[4] Inst Curie, Dept Biometry, St Cloud, France

[5] Inst Curie, Dept Med Oncol, St Cloud, France

[6] Ctr Georges Francois Leclerc, Dept Med Oncol, Dijon, France

[7] Ctr Leon Berard, Dept Med Oncol, Lyon, France

[8] Clin Univ St Luc, Dept Med Oncol, Brussels, Belgium

[9] Ctr Francois Baclesse, Dept Med Oncol, Caen, France

[10] Ctr Jean Perrin, Dept Med Oncol, Clermont Ferrand, France

[11] IUCT Oncopole Toulouse, Inst Claudius Regaud, Dept Med Oncol, Toulouse, France

[12] ICO Inst Cancerol Ouest Rene Gauducheau, Dept Med Oncol, St Herblain, France

[13] Inst Jean Godinot, Dept Med Oncol, Reims, France

[14] Limoges Univ Hosp, Dept Med Oncol, Limoges, France

[15] Ctr Hosp Pau, Dept Med Oncol, Pau, France

[16] Ctr Antoine Lacassagne, Dept Med Oncol, Nice, France

[17] Grand Hop Charleroi, Dept Oncol Hematol, Charleroi, Belgium

[18] Inst St Catherine, Dept Med Oncol, Avignon, France

[19] Inst Curie, Dept Tumor Biol, Pharmacogen, Paris, France

[20] Inst Curie, Translat Res Dept, Genom Platforms, Paris, France

[21] Unicancer, R&D, Paris, France

[22] Inst Curie, Tumour Biol Dept, Paris, France

[23] Gustave Roussy Canc Campus, Dept Med Oncol, Villejuif, France

来源：

ANNALS OF ONCOLOGY | 2018年 / 29卷 / 12期

关键词：

luminal breast cancer; palbociclib; neoadjuvant; PAM50; KINASE; 4/6; INHIBITOR; ENDOCRINE THERAPY; DECISIONS;

D O I：

10.1093/annonc/mdy448

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Palbociclib is a CDK4/6 inhibitor with demonstrated efficacy and safety in combination with endocrine therapy in advanced luminal breast cancer (LBC). We evaluated the respective efficacy and safety of chemotherapy and letrozole-palbociclib (LETPAL) combination as neoadjuvant treatment in patients with high-risk LBC. NeoPAL (UCBG10/4, NCT02400567) is a randomised, parallel, non-comparative phase II study. Patients with ER-positive, HER2-negative, Prosigna(A (R))-defined luminal B, or luminal A and node-positive, stage II-III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks, or to FEC100 (5FU 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2))x3 21-day courses followed by docetaxel 100 mg/m(2)x3 21-day courses. Primary end point was residual cancer burden (RCB 0-I rate). Secondary end points included clinical response, proliferation-based markers, and safety. Overall, 106 patients were randomised [median Prosigna(A (R)) ROR Score 71 (22-93)]. RCB 0-I was observed in four and eight patients in LETPAL [7.7% (95% CI 0.4-14.9)] and chemotherapy [15.7% (95% CI 5.7-25.7)] arms, respectively. Pathological complete response rates were 3.8% and 5.9%. Clinical response (75%) and breast-conserving surgery rates (69%) were similar in both arms. Preoperative Endocrine Prognostic Index 0 scores (breast cancer-specific survival) were observed in 17.6% and 8.0% of patients in LETPAL and chemotherapy arms, respectively. Safety profile was as expected, with 2 versus 17 serious adverse events (including 11 grade 4 serious AEs in the chemotherapy arm). LETPAL combination was associated with poor pathological response but encouraging clinical and biomarker responses in Prosigna(A (R))-defined high-risk LBC. Contemporary chemotherapy regimen was associated with poor pathological and biomarker responses, with a much less favourable safety profile. LETPAL combination might represent an alternative to chemotherapy in early high-risk LBC. NCT02400567.

引用

页码：2334 / 2340

页数：7

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