Suzette Delaloge1, Sylvain Dureau2, Véronique D'Hondt3, Isabelle Desmoulins4, Pierre-Etienne Heudel5, Francois P Duhoux6, Christelle Levy7, Florence Lerebours8, Marie A Mouret-Reynier9, Florence Dalenc10, Jean-Sébastien Frenel11, Christelle Jouannaud12, Laurence Venat-Bouvet13, Suzanne Nguyen14, Cécile Callens15, David Gentien15, Audrey Rapinat15, Helene Manduzio16, Anne Vincent-Salomon15, Jérôme Lemonnier16, Paul Cottu17. 1. Department of Cancer Medicine, Gustave Roussy, Villejuif, France. Electronic address: suzette.delaloge@gustaveroussy.fr. 2. Department of Biostatistics, Institut Curie, Paris, France. 3. Department of Medical Oncology, Institut du Cancer Montpellier, Montpellier, France. 4. Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France. 5. Department of Medical Oncology, Centre Leon Berard, Lyon, France. 6. Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 7. Department of Medical Oncology, Centre François Baclesse, Caen, France. 8. Department of Medical Oncology, Curie Institute, Saint Cloud, France. 9. Department of Medical Oncology, Centre Jean Perrin, Clermont Ferrand, France. 10. Department of Medical Oncology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France. 11. Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes, France. 12. Department of Medical Oncology, Institut Godinot, Reims, France. 13. Department of Medical Oncology, CHU Limoges, Limoges, France. 14. Medical Oncology, Centre Hospitalier de Pau, Pau, France. 15. Research Centre, Department of Translational Research, Genomics Platform, Institut Curie, Paris Sciences et Lettres Research University, Paris, France. 16. R&D Unicancer, Paris, France. 17. Department of Medical Oncology, Institut Curie & PSL University, Paris, France.
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.
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: Vera J Suman; Lili Du; Tanya Hoskin; Meenakshi Anurag; Cynthia Ma; Isabelle Bedrosian; Kelly K Hunt; Matthew J Ellis; W Fraser Symmans Journal: Clin Cancer Res Date: 2022-08-02 Impact factor: 13.801