I. Desmoulins (Dijon, Ce, France)
Centre Georges-François Leclerc (Dijon)Author Of 1 Presentation
63O - Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: survival results of the UNICANCER-NeoPAL study (ID 239)
Abstract
Background
The NeoPAL trial compared letrozole-palbociclib (LETPAL) combination to standard chemotherapy (CT) as neoadjuvant treatment in patients with high-risk LBC. Both LETPAL and CT were associated with poor pathological response, and equivalent clinical responses, while LETPAL let to encouraging biomarker responses in Prosigna®-defined high-risk LBC. We now evaluate the survival outcomes of both groups.
Methods
NeoPAL (UCBG104, NCT02400567) is a randomized, parallel, non-comparative phase II study. Postmenopausal women with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III BC, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks (LETPAL), or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) x3 21-day courses followed by docetaxel 100 mg/m2 x3 21-day courses (CT). Secondary endpoints included progression-free survival (PFS) and invasive-disease free survival (iDFS), all measured from the date of randomization. Exploratory objectives aimed at evaluating the impact of PEPI score and residual cancer burden (RCB) on survival outcomes in both arms.
Results
53 pts were randomized in each arm. 23 of the 53 pts in the LETPAL arm received postoperative adjuvant chemotherapy. Median follow-up is 40.4 months [0-56.6]. 11 progressions have been observed, of which 3 were in the LETPAL and 8 in the control arm. Two additional iDFS events were observed in the LETPAL arm (secondary malignancies). 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. 40 months PFS rate is 86.7% (78.0-96.4) and 87.2% (78.1-97.4) in LETPAL and CT arms respectively. PEPI (PEPI II/II vs I: HR 0.80, 95%CI 0.18-3.67) and RCB scores (RCB II/III vs 0/I: HR 1.36; 95%CI 0.17-10.6) did not appear as independent predictors of PFS or iDFS.
Conclusions
Despite its small size, NeoPAL suggests that a neoadjuvant LETPAL strategy, together with selected postoperative administration of chemotherapy, may spare chemotherapy in some pts with LBC while allowing good long-term outcomes.
Clinical trial identification
NCT02400567.
Legal entity responsible for the study
UNICANCER.
Funding
Pfizer, NanoString Technologies.
Disclosure
S. Delaloge: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Orion; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Pierre Fabre. H. Manduzio, J. Lemonnier, P.H. Cottu: Research grant/Funding (institution): Pfizer. All other authors have declared no conflicts of interest.
Author Of 1 Presentation
- A. Schmitt (Dijon, France)
- M. Reda (Dijon, France)
- P. Macaire (Dijon, France)
- H. Bellio (Dijon, France)
- L. Uwer (Vandoeuvre les Nancy, CE, France)
- S. Ilie (Dijon, Se, France)
- V. Lorgis (Dijon, Ce, France)
- A. Hennequin (Dijon, France)
- S. Ladoire (Dijon, Ce, France)
- E. Rederstorff (Dijon, France)
- P. Fumoleau (Paris, Ce, France)
- N. Isambert (Dijon, Ce, France)
- N. Bonnin (Pierre Benite, CE, France)
- B. You (Pierre Benite, France)
- G. Freyer (Pierre Benite, CE, France)
- I. Desmoulins (Dijon, Ce, France)
147P - When a single G-CSF administration is better than longer duration: example in patients treated by eribulin
Abstract
Background
Granulocyte colony-stimulating factors (G-CSF) are commonly given to limit chemotherapy-induced neutropenia. However, for weekly chemotherapy such as eribulin, their administration schedules remain empirical. This pharmacokinetic/pharmacodynamic (PK/PD) study was conducted to establish the effect of different G-CSF regimens on neutropenia’s incidence for patients treated by eribulin, to propose an optimal G-CSF dosing schedule.
Methods
A semi-physiological population PK/PD neutropoiesis model was developed from absolute neutrophil counts (ANC) obtained in 87 cancer patients receiving eribulin for two cyccles. The structural model considered ANC dynamics, neutropenic effect of eribulin and the stimulating effect of G-CSF on neutrophils. Final model parameters were used to calculate the incidence of neutropenia following different G-CSF dosing schedules for 1’000 virtual subjects.
Results
The final model successfully described the ANC time-course for all patients. Simulations showed that a single G-CSF administration 48h after each eribulin injection reduced the risk of severe neutropenia from 29.7% to 5.2%. G-CSF administration after the 2nd eribulin injection was responsible for similar incidence of neutropenia compared to absence of administration.
Conclusions
The PK/PD model well described our population's ANC data. Simulations showed a single G-CSF administration 48 hours after the end of each chemotherapy seems to be the optimal schedule to reduce eribulin-induced neutropenia.
Clinical trial identification
Eudract 2015-001753-32, 2015/01/26.
Legal entity responsible for the study
Centre Georges-François Leclerc.
Funding
Eisai.
Disclosure
G. Freyer: Speaker Bureau/Expert testimony: Eisai. All other authors have declared no conflicts of interest.