Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer.

Abstract

BACKGROUND:

Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes.

METHODS:

Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy.

RESULTS:

Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months [0-56.6], 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; [95%CI 0.36-2.90], p = 0.98) and iDFS (HR = 0.83; [95%CI 0.31-2.23], p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% [95%CI 78.0-96.4] and 89.9% [95%CI 81.8-98.7] in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it.

CONCLUSIONS:

NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed.

• Authors: Suzette Delaloge, Sylvain Dureau, Véronique D'Hondt, Isabelle Desmoulins, Pierre-Etienne Heudel, Francois P Duhoux, Christelle Levy, Florence Lerebours, Marie A Mouret-Reynier, Florence Dalenc, Jean-Sébastien Frenel, Christelle Jouannaud, Laurence Venat-Bouvet, Suzanne Nguyen, Cécile Callens, David Gentien, Audrey Rapinat, Helene Manduzio, Anne Vincent-Salomon, Jérôme Lemonnier, Paul Cottu, French Breast cancer Intergroup Unicancer-UCBG
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 166 Pg. 300-308 (05 2022) ISSN: 1879-0852 [Electronic] England
• PMID: 35337692 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Piperazines
• Pyridines
• Receptors, Estrogen
• Letrozole
• Receptor, ErbB-2
• palbociclib

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (drug therapy, pathology)
• Female
• Humans
• Letrozole
• Neoadjuvant Therapy (adverse effects)
• Piperazines
• Pyridines
• Receptor, ErbB-2
• Receptors, Estrogen
• Survival Analysis