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

• Published in: European journal of cancer (1990) Vol. 166; pp. 300 - 308
• Main Authors: Delaloge, Suzette, Dureau, Sylvain, D'Hondt, Véronique, Desmoulins, Isabelle, Heudel, Pierre-Etienne, Duhoux, Francois P., Levy, Christelle, Lerebours, Florence, Mouret-Reynier, Marie A., Dalenc, Florence, Frenel, Jean-Sébastien, Jouannaud, Christelle, Venat-Bouvet, Laurence, Nguyen, Suzanne, Callens, Cécile, Gentien, David, Rapinat, Audrey, Manduzio, Helene, Vincent-Salomon, Anne, Lemonnier, Jérôme, Cottu, Paul
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2022; Elsevier Science Ltd; Elsevier
• Subjects: Anthracycline; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer therapies; CDK4/6 inhibitor; Chemotherapy; Endocrine therapy; ErbB-2 protein; Female; Humans; Invasiveness; Letrozole; Life Sciences; Luminal breast cancer; Neoadjuvant; Neoadjuvant Therapy - adverse effects; Patients; Piperazines; Post-menopause; Progressions; Pyridines; Receptor, ErbB-2; Receptors; Receptors, Estrogen; Survival; Survival Analysis; Neoadjuvant; Chemotherapy; Survival; CDK4/6 inhibitor; Luminal breast cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.01.014

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.
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.
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.
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.
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•First CDK4/6 neoadjuvant randomised trial to report survival outcomes.•NEOPAL trial compared neoadjuvant Letrozole Palbociclib versus chemotherapy.•Pathological complete response rates were identically low (3.8% and 5.9%, respectively).•Progression-free survival (HR = 1.01; [95%CI 0.36–2.90], p = 0.98) did not differ between both arms.•Invasive disease-free survival (HR = 0.83; [95%CI 0.31–2.23], p = 0.71) did not differ between both arms.