A. Vincent-Salomon (Paris, France)
Institut CurieAuthor Of 2 Presentations
Evaluation of HER2 status: What else needs to be known (ID 296)
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.
Presenter Of 1 Presentation
Evaluation of HER2 status: What else needs to be known (ID 296)
Author Of 1 Presentation
- C. CHALUMEAU (Saint cloud, France)
- J. Pierga (Paris, CE, France)
- G. Pierron (Paris, France)
- S. Ballet (Paris, France)
- S. Nasr (Paris, France)
- A. Vincent-Salomon (Paris, France)
- P. Vuagnat (Saint cloud, France)
- A. Bellesoeur (Paris, France)
- M. Carton (Saint-Cloud, France)
- F. Bidard (Paris, CE, France)
- F. Lerebours (St. Cloud, France)
113P - Efficacy of oral etoposide associated with trastuzumab in HER2-positive metastatic breast cancer: results from the Institut Curie’s database.
Abstract
Background
The TOP2A (encoding topoisomerase II) and HER2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. The topoisomerase-II inhibitor etoposide (oral VP16) has demonstrated clinical activity in metastatic breast cancer (MBC). However, the clinical benefit of trastuzumab combined with oral VP16 (T-VP16) in HER2+ MBC has not been evaluated.
Methods
Patients treated at Institut Curie Hospitals (Paris and Saint Cloud, France) with T-VP16 for HER2+ MBC were retrieved by an in-silico search. A waiver of informed consent was obtained from the local IRB. Clinical and pathological data were collected by trained medical oncologists. The primary study endpoint was progression-free survival (PFS) assessed by the Kaplan Meier method. Secondary endpoints were: overall survival (OS), long response rate (PFS>6 months), clinical benefit (defined as a PFS than 6 months AND longer than the PFS achieved by the previous line of treatment), response rate, and toxicity.
Results
From 2008 to 2016, 43 patients with HER2+ MBC who received T-VP16 were included. The median number of previous chemotherapy lines was 7 (range 1-13). The median PFS and OS were 2.9 months (95% CI [2.4-4.7]) and 11.3 months (95% CI [8.3-25.0]), respectively. Twelve patients (27.9%) had a long response to treatment including nine (20.9%) with clinical benefit. A complete response was obtained for 3 patients. Only 4 patients stopped treatment for toxicity.
Conclusions
The favorable clinical benefit, good tolerance and low cost suggest that T-VP16 is a relevant option for patients with heavily pretreated HER2-positive MBC. TOP2A and HER2 co-amplification data will be presented at the meeting.
Legal entity responsible for the study
Institut Curie.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.