Systemic Therapy Considerations in Inflammatory Breast Cancer

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Ethel Underwood
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1 Systemic Therapy Considerations in Inflammatory Breast Cancer Shani Paluch-Shimon, MBBS, MSc Director, Breast Oncology Unit Shaare Zedek Medical Centre, Jerusalem Israel

2 Disclosures Roche: Speakers bureau, honoraria, consultancy Astra Zeneca: Speakers bureau, honoraria, consultancy Novartis: Speakers bureau, honoraria, consultancy Pfizer: Speakers bureau, honoraria, consultancy

3 IBC 1-6% of all new BC Clinical diagnosis erythema & dermal edema of 1/3 of the breast Dermal lymphatic invasion neither required not sufficient for the Dx = ct4d Usually HR-negative, often HER2+ - commonly Basal & HER2 subtype Needs a systemic work up Multi-modality care - MUST

4 Pierga et al, Annals of Oncology 2017

5 Prognosis Overall and event-free survival. (A) Overall survival (n = 107). (B) Overall survival by stage of disease: stage IIIA (n = 48) versus stage IIIB inflammatory breast cancer (IBC; n = 46), P =.0046; stage IIIA versus stage IIIB non-ibc (NIBC; n = 13), P =.018 Low et al,jco, 2004

6 Prognosis by subtype Li et al, Oncotarget, 2017

7 Prognosis by response to NAST & subtype Masuda et al, Annals of Oncology, 2013

8 Dawood, Annals of Oncology, 2014

9 Pre-operative treatment local recurrence distance recurrence

10 Chemotherapy

11 Anthracyclines & Taxanes backbone of chemotherapy Dawood et al, Annals of Oncology, 2010

12 HER2+ IBC

13 Anti-HER2 therapy 1 st generation study - NOAH included IBC 2 nd generation studies - Neo-ALTTO excluded IBC - NeoSphere included IBC

14 NOAH (MO16432): Study design An international, open-label, Phase III study of neoadjuvant adjuvant Herceptin (trastuzumab) in patients with locally advanced or inflammatory HER2-positive breast cancer HER2-positive LABC (IHC 3+ or FISH-positive) HER2-negative LABC (IHC 0/1+) a (n=117) (n=118) (n=99) H + AP q3w x 3 cycles AP q3w x 3 cycles AP q3w x 3 cycles H + P q3w x 4 cycles P q3w x 4 cycles P q3w x 4 cycles H q3w x 4 cycles + CMF q4w x 3 cycles CMF q4w x 3 cycles CMF q4w x 3 cycles H continued q3w to week 52 Surgery followed by radiotherapy b 19 crossed over to H H, Herceptin (trastuzumab) (8 mg/kg loading dose then 6 mg/kg) AP, doxorubicin (60 mg/m 2 ), paclitaxel (150 mg/m 2 ); P, paclitaxel (175 mg/m 2 ) CMF, cyclophosphamide, methotrexate, and fluorouracil; a A separate treatment group of HER2-negative patients received chemotherapy only; b Hormone receptor-positive patients received adjuvant tamoxifen Gianni et al 2010

15 NOAH: Baseline characteristics Stage group, % Patients with HER2-positive disease Herceptin (trastuzumab) + chemotherapy (n=117) Chemotherapy (n=118) T4, non-inflammatory Inflammatory disease N2 or ipsilateral nodes Hormone receptor status, % ER- and/or PR-positive Both negative Age group, % <50 years years Gianni et al 2010

17 NOAH Trial: Preoperative Chemo +/- Trastuzumab for LABC Gianni L, et al; Lancet 2010

18 bpcr, % ± 95% CI pcr, % ± 95% CI NeoSphere: study design and pcr results Patients with operable or locally advanced/ inflammatory HER2-positive BC Chemo-naive & primary tumors >2 cm (N=417) TD (n=107) trastuzumab (8 6 mg/kg) docetaxel ( mg/m 2 ) PTD (n=107) pertuzumab ( mg) trastuzumab (8 6 mg/kg) docetaxel ( mg/m 2 ) PT (n=107) pertuzumab ( mg) trastuzumab (8 6 mg/kg) PD (n=96) pertuzumab ( mg) docetaxel ( mg/m 2 ) Study dosing: q3w x 4 S U R G E R Y p = p = p = TD PTD PT PD HR-positive HR-negative TD PTD PT PD bpcr tpcr HR, hormone receptor; HR-positive = estrogen and/or progesterone receptor-positive; HR-negative = estrogen and progesterone receptor-negative Gianni L, et al. Lancet Oncol 2012; 13:

19 Patient baseline characteristics, ITT population TD (n=107) PTD (n=107) PT (n=107) PD (n=96) Median age, years (range) 50 (32 74) 50 (28 77) 49 (22 80) 49 (27 70) ECOG PS, % HR-positive (ER- and/or PR-positive), % HR-negative (ER- and PR-negative), % Operable, % Locally advanced, % Inflammatory, % ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; PR, progesterone receptor Gianni L, et al. Lancet Oncol 2012; 13:25 32

20 Future Directions Genomic profile of IBC: - Genomic instability - Immune infiltrate - PDL1 over-expression - DNA MMR (Hamm et al Mol Cancer Therapeutics, 2016) Targeting other pathways? - angiogenesis? Bevacizumab - mtor/akt - JAK/STAT - Cell cyle/myc - EGFR Immunotherapy?

21 Guidelines

25 In conclusion Systemic therapy should be guided by subtype and stage: Stage III aim cure: - HER2-negative disease anthracycline-taxane based chemotherapy - HER2+ disease Chemotherapy + dual blockade followed by year of anti- HER2 therapy Stage IV disease aim prolong life and palliate - Tailor treatment to symptoms, subtype Clinical trials!!! This is an orphan disease

26 Thank you

Neo-adjuvant and adjuvant treatment for HER-2+ breast cancer

Neo-adjuvant and adjuvant treatment for HER-2+ breast cancer Angelo Di Leo «Sandro Pitigliani» Medical Oncology Unit Hospital of Prato Istituto Toscano Tumori Prato, Italy NOAH: Phase III, Open-Label Trial