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

Abstract

Background:

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.

Patients and methods:

NeoPAL (UCBG10/4, NCT02400567) is a randomised, parallel, non-comparative phase II study. Patients with ER-positive, HER2-negative, Prosigna®-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/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2)×3 21-day courses followed by docetaxel 100 mg/m2×3 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.

Results:

Overall, 106 patients were randomised [median Prosigna® 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).

Conclusion:

LETPAL combination was associated with poor pathological response but encouraging clinical and biomarker responses in Prosigna®-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.

Clinical Trial Number:

NCT02400567.

• Authors: P Cottu, V D'Hondt, S Dureau, F Lerebours, I Desmoulins, P-E Heudel, F P Duhoux, C Levy, M-A Mouret-Reynier, F Dalenc, J-S Frenel, C Jouannaud, L Venat-Bouvet, S Nguyen, J-M Ferrero, J-L Canon, J Grenier, C Callens, D Gentien, J Lemonnier, A Vincent-Salomon, S Delaloge
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 29 Issue 12 Pg. 2334-2340 (12 01 2018) ISSN: 1569-8041 [Electronic] England
• PMID: 30307466 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Biomarkers, Tumor
• Piperazines
• Protein Kinase Inhibitors
• Pyridines
• Letrozole
• palbociclib

Topics

• Aged
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Biomarkers, Tumor (analysis, genetics)
• Breast (pathology, surgery)
• Breast Neoplasms (mortality, pathology, therapy)
• Disease-Free Survival
• Female
• Gene Expression Profiling
• Humans
• Letrozole (administration & dosage, adverse effects)
• Mastectomy, Segmental
• Middle Aged
• Neoadjuvant Therapy (methods)
• Neoplasm Staging
• Patient Selection
• Piperazines (administration & dosage, adverse effects)
• Prognosis
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pyridines (administration & dosage, adverse effects)