Authors : Paul cottu, Véronique D'Hondt; Sylvain Dureau; Florence Lerebours; Isabelle Desmoulins; Pierre-Etienne Heudel; François P Duhoux; Christelle Levy; Marie-Ange Mouret-Reynier; Florence Dalenc; Jean-Sébastien Frenel; Christelle Jouannaud; Laurence Venat-Bouvet; Suzanne Nguyen; Jean-Marc Ferrero; Jean-Luc Canon; Julien Grenier; Céline Callens; David Gentien; Jérôme Lemonnier; Anne Vincent-Salomon; Suzette Delaloge
Ann Oncol. 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448.
Experts group or program : French Breast Cancer Intergroup (UCBG)
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
