SAMO FoROMe Post-ESMO 2013 Breast Cancer

Transcription

1 SAMO FoROMe Post-ESMO 2013 Breast Cancer Dr. med. Manuela Rabaglio Klinik und Poliklinik für Medizinische Onkologie

2 Breast Cancer Track 300 Abstracts 142 Poster 11 Proffered paper 4 late breaking news 1 best abstract (Presidential section) Debate/Special Sections/Teaching Sections SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 2

3 Outline Adjuvant endocrine treatment Local treatment (surgery/radiotherapy) Bisphosphonate Targeted treatment Miscellaneus SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 3

4 Adjuvant endocrine treatment attom trial: A randomised comparison of continuing adjuvant tamoxifen to 10 years compared to stopping after 5 years in 6953 women with ER positive or ER untested early breast cancer attom confirms the findings of the complementary ATLAS study that, continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in recurrence and breast cancer deaths. The proportional reduction in recurrence was unaffected by age or nodal status. Benefits from continuing tamoxifen treatment beyond year 5 emerge only after 7 years from start of treatment for recurrence and 10 years for mortality. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 4

5 Adjuvant endocrine treatment after 5 years Patient wish and acceptance Side effects Premenopausal women (at diagnosis) Still premenopausal : consider continuing TAM (5 y) Postmenopausal: consider switching to AI (5y) Postmenopausal women After 5 years TAM switch to AI for 5 years After TAM/AI, complete 5 years AI After 5 years AI -? SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 5

6 Radiotherapy/Local Therapy BEST ABSTRACT: Irradiation of the internal mammary and medial supraclavicular lymph nodes in stage I to III breast cancer: 10 years results of the EORTC Radiation Oncology and Breast Cancer Groups phase III trial 22922/ vs. 80.7% OS (HR=0.87 (95%CI: 0.76, 1.00), Logrank p=0.056); 72.1 vs. 69.1% DFS (HR=0.89 (95%CI: 0.80, 1.00), Logrank p=0.044) AMAROS trial: Axillary lymph node dissection versus axillary radiotherapy A detailed analysis of morbidity. Surgical complications were observed in 23% of the patients in the ALND-group versus 9% in the ART-group (P<0.001). SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 6

7 Radiotherapy/Local Therapy In two independent randomized trials young high risk breast cancer patients with luminal A tumors had benefit from postmastectomy radiation therapy (British Columbia Trial and DBCG82b Trial) Intrinsic subtypes define using PAM50 criteria No difference in OS SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 7

8 Radiotherapy/Local Therapy Can breast IMRT improve patient reported outcome measures? Contrary to clinician assessed outcome, breast IMRT did not translate in to improved Patient reported outcome measures (PROMs) in this study. Only a small proportion of patients reported moderate-severe breast changes post radiotherapy with most PROMs improving over time. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 8

9 This House Believes That Axillary Dissection Should be Avoided in Patients With Positive Sentinel Node (Prof M. Gnant) ACOSOG-Z0011 is a great clinical trial The results are not suitable for defining a new standard of care, and must not be abused for surgeons marketing purposes. In principle, ALND remains the standard of care for patients with positive sentinel node However it has become easier to waive additional axillary surgery in borderline cases (age, 2nd procedure, comorbidity, several micromets, ezc) Understanding Z0011 results helps in moving forward the field of breast cancer from numeric issues to the biology of the disease. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 9

10 Radiotherapy/Local Therapy Still open questions: ALND in patient with positive sentinel node Radiation therapy of the axilla Postmastectomy RT Radiation therapy of the internal mammary and supraclavicular IMRT Intraoperative RT Partial breast RT More RT vs less surgery? Role of systemic therapy? SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 10

11 Bisphosphonate (Neoadjuvant/ Adjuvant) NEOZOTAC randomized study comparing the efficacy of TAC with or without ZA 4mg i.v. q 3 weeks in patients (pts) with stage II/III, HER2 neg BC neo-adjuvant Treatment with ZA did not make a difference as regards clinical response nor pcr. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 11

12 Adjuvant therapy in early breast cancer with zoledronic acid (AZURE - BIG 01/04): Final efficacy analysis ZOL reduced disease recurrence in bone and, consistent with other studies, had a favourable effect on both invasive DFS and OS in postmenopausal women (LM > 5 year) However, an excess of events outside bone in all other women resulted in no overall effect of ZOL on disease outcomes in the total study population. An EBCTCG meta-analysis is in progress to guide treatment recommendations. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 12

13 AZURE - BIG 01/04 SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 13

14 Targeted Treatment: SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 14

15 Targeted Treatment: SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 15

16 Targeted Treatment: Primary results from TH3RESA: a phase 3 study of T-DM1 vs treatment of physician's choice in HER2-positive metastatic breast cancer (MBC): T-DM1 resulted in a statistically significant improvement in PFS, with fewer grade 3 AEs than TPC in pts previously treated with 2 HER2-directed regimens for HER2-positive MBC. OS 14.9 mos for TPC, not reached for T-DM1 Remaining issues are the optimal sequencing of HER2- directed therapies and the best role for T-DM1 (discussant Clifford Hudis) SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 16

17 Targeted Treatment SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 17

18 Targeted Treatment The LEA study failed to demonstrate a statistically significant increase in PFS by adding bevacizumab to ET as first line therapy in metastatic breast cancer OS was also not impacted. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 18

19 Trastuzumab Resistance BOLERO-3 trial: Evaluation of everolimus (EVE) in HER2+ advanced breast cancer (BC) with activated PI3K/mTOR pathway Patient with PI3K/mTOR pathway activation may derive greater benefit from addition of EVE to trastuzumab and vinorelbine. These observations are consistent with the hypothesis that mtor inhibition attenuates trastuzumab resistance resulting from PI3K/mTOR pathway activation. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 19

20 Trastuzumab/Lapatinib Resistance- Role of PI3KCA PI3KCA mutations and correlation with pcr in the NeoALTTO trial (BIG 01-06) (Abstr. 1859) In patients treated with the combination of lapatinib and trastuzumab, the pathologic complete response rate was 55.8% in those lacking PIK3CA mutations but only 28.6% in those with mutant tumors (P =.02) The lower pathologic complete response rate in PI3KCAmutant tumors is observed in all treatment arms and irrespective of estrogen receptor status PIK3CA mutations were found in 23% of patients Thus, assessment of PIK3CA status might be an important tool in identifying patients unlikely to derive substantial benefit from these treatments. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 20

21 Lapatinib: Rash and response rate Pattern of rash, diarrhea, and hepatic toxicities secondary to neoadjuvant lapatinib and their association with age and pathological complete response (pcr) in breast cancer (BC) patients: Analysis from the NeoALTTO trial (Abstr. 1868) Rash is more common in young pts receiving lapatinib In addition, early development of rash is associated with a higher chance of achieving pcr, independent of age, treatment arm and other clinicopathologic features. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 21

22 New strategies PARP inhibition with BMN 673 in ovarian and breast cancer patients with deleterious mutations of BRCA1 and BRCA2 18 Breast: CR 1 (6%) PR 9 (50%) SD > 12 weeks 4 (22%) CBR 14 (78%) BMN 673 is well tolerated with high objective and clinical benefit response rates in heavily pre-treated ovarian and breast cancer pts with deleterious germ line BRCA mutations. A phase 3 trial in metastatic breast cancer is underway. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 22

23 Liquid Biopsy Circulating tumor cells before and during therapy in metastatic breast cancer Liquid Biopsy This large pooled analysis has a previously unreached statistical power and provides level-of-evidence 1 on the independent prognostic value of CTCs before and during treatment in MBC. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 23

24 Intertumoral and intratumoral heterogeneity Histology ER, PgR, HER2 Transcription profiling Genome sequencing Proteomics Luminal A Luminal B HER2+ Basal like Claudin-low Molecular Apocrine 6 TNBC subtypes Basal-like 1 (BL1) Basal-like 2 (BL2) Immunomudulatory (IM) Mesenchymal (M) Mesenchymal stem-like (MSL) Luminal androgen receptor (LAR) SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 24

25 Intratumoral heterogeneity Population based study investigating biopsy verifications of "breast cancer recurrences" and biomarker changes discordance of biomarkers between the primary tumor and the corresponding relapse in 10 40%. Patients with loss of ER or PR in relapse have poorer survival compared to patients with stable positive biomarkers. Indeed, adjuvant therapy may affect the loss of hormonal receptors. Do we need to perform biopsy of recurrent disease? Role of CTC? Role of genome sequencing and proteomics? SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 25

26 Physical activity Pre- and postdiagnostic physical activity levels in relation to breast cancer outcome in postmenopausal breast cancer patients - results of the TEAM-lifestyle study Overall survival was higher in patients who had increased levels of PA, pre- or postdiagnostically, while no statistically significant association was observed for BC recurrence and BC specific survival. SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 26

27 Thank you SAMO FoROMe Post-ESMO 2013/ Dr. Manuela Rabaglio 27