I SOTTOGRUPPI FENOTIPICI E I RISULTATI SINORA RAGGIUNTI. Marta Bonotto Department of Oncology, University Hospital of Udine, Italy
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1 I SOTTOGRUPPI FENOTIPICI E I RISULTATI SINORA RAGGIUNTI Marta Bonotto Department of Oncology, University Hospital of Udine, Italy
2 Breast Cancer
3 Metastatic Breast Cancer (MBC)
4 Metastatic Breast Cancer (MBC)
5 Metastatic Breast Cancer (MBC)
6 Metastatic Breast Cancer (MBC): subtypes HR MBC HER2
7 Metastatic Breast Cancer (MBC): subtypes HR + MBC TN HER2 +
8 Metastatic Breast Cancer (MBC): subtypes TN MBC HR + HER2 +
9 Metastatic Breast Cancer (MBC): subtypes Triple negative Luminal A Non Luminal HER2 Luminal HER2 Luminal B
10 Metastatic Breast Cancer (MBC): outcomes OS = PFS + SPP If the progression event is death, then SPP = 0 Broglio KR & Berry DA, J Natl Cancer Inst, 2009
11 Metastatic Breast Cancer (MBC): outcomes Event: death Event: death OS = PFS + SPP If the progression event is death, then SPP = 0 Broglio KR & Berry DA, J Natl Cancer Inst, 2009
12 Metastatic Breast Cancer (MBC): outcomes Events: death progression (imaging, biochemical examination, clinical visit) Event: death Event: death OS = PFS + SPP If the progression event is death, then SPP = 0 Broglio KR & Berry DA, J Natl Cancer Inst, 2009
13 Metastatic Breast Cancer (MBC): outcomes PFS1 PPS1 PFS2 PPS2 PFS n PPS n OS
14 OS estimation according to subtypes: REAL WORLD Luminal A Luminal B HER2 positive Triple negative Bonotto M. Oncologist 2014
15 Metastatic Breast Cancer (MBC): subtypes MBC HR + HER2 + Proliferation index? TN
16 OS estimation according to subtypes: REAL WORLD Luminal A Luminal B HER2 positive Triple negative Bonotto M. Oncologist 2014
17 Metastatic Breast Cancer (MBC): subtypes MBC HR + HER2 + Proliferation index?? TN
18 OS estimation according to subtypes: REAL WORLD Bonotto M. Oncologist 2014
19 REAL WORLD SCENARIO OS N Median (mo) Luminal A Luminal B HER2 positive HER2 pos, ER and/or PgR pos HER2 pos, ER and PgR neg Triple Negative No triple negative PFS1 Luminal A Luminal B HER2 positive HER2 pos, ER and/or PgR pos HER2 pos, ER and PgR neg Triple Negative No triple negative PPS1 Luminal A Luminal B HER2 positive HER2 pos, ER and/or PgR pos HER2 pos, ER and PgR neg Triple Negative No triple negative Bonotto M. Oncologist 2014
20 Hypothetical scenarios for expected survival Seidman AD. J Clin Oncol 2018
21 REAL WORLD SCENARIO Bonotto M. Oncologist 2014
22 Phase III pivotal trial for MBC patients HR + Trial Drugs Control Line Primary Endpoint BOLERO-2 Baselga PALOMA-2 Finn PALOMA-3 Turner MONALEESA Hortobagyi MONARCH 2 Sledge MONARCH 3 Goetz CALGB Dickler Results (months) Exe+eve exe 2nd PFS 10.6 vs 4.1 (HR 0.36; 95% CI, ; P <.001) Letro+palbo letro 1st PFS 24.8 vs 14.5 (HR 0.58; 95% CI, ; P <.001) Fulv+palbo fulv 2nd PFS 9.5 vs 4.6 (HR 0.46; 95% CI, ; P <.001) Letro+ribo letro 1st PFS 63% vs 43.3% (18-mo PFS) (HR 0.56; 95% CI, ; P <.001) Fulv+abema fulv 2nd PFS 16.4 vs 9.3 (HR 0.55; 95% CI, ; P <.001) AI+abema AI 1st PFS HR 0.54; 95% CI, 0.41 to 0.72; P <.001) letro+bev letro 1st PFS 20.2 vs 15.6 (HR 0.75; 95% CI, 0.59 to 0.96; P =.016)
23 Phase III pivotal trial for MBC patients HR + Trial Drugs Control Line Primary Endpoint BOLERO-2 Baselga PALOMA-2 Finn PALOMA-3 Turner MONALEESA Hortobagyi MONARCH 2 Sledge MONARCH 3 Goetz CALGB Dickler Results (months) Exe+eve exe 2nd PFS 10.6 vs 4.1 (HR 0.36; 95% CI, ; P <.001) Letro+palbo letro 1st PFS 24.8 vs 14.5 (HR 0.58; 95% CI, ; P <.001) Fulv+palbo fulv 2nd PFS 9.5 vs 4.6 (HR 0.46; 95% CI, ; P <.001) Letro+ribo letro 1st PFS 63% vs 43.3% (18-mo PFS) (HR 0.56; 95% CI, ; P <.001) Fulv+abema fulv 2nd PFS 16.4 vs 9.3 (HR 0.55; 95% CI, ; P <.001) AI+abema AI 1st PFS HR 0.54; 95% CI, 0.41 to 0.72; P <.001) letro+bev letro 1st PFS 20.2 vs 15.6 (HR 0.75; 95% CI, 0.59 to 0.96; P =.016)
24 Phase III pivotal trial for MBC patients HER2 + Trial Drugs Control Line Primary Endpoint CLEOPATRA Swain EMILIA Verma EGF30008 Geyer Results (months) Doce+trast+pert Doce+trast 1st PFS 18.5 vs 12.8 (HR 0.62; 95% CI, ; P <.001) Letro+palbo Cape+trast 2nd PFS 9.6 vs 6.4 (HR 0.65; 95% CI, ; P<.001) cape+lapatinib Cape 2nd TTP 5.4 vs 4.2 (HR 0.72; 95% CI, ; P =.008) EGF30008 Johnston PERTAIN Arpino Letro+lapatinib Letro 1st PFS 8.2 vs 3.0 (HR 0.71; 95% CI, ; P =.019) Ai+trast+pert Ai+trast 1st PFS 18.9 vs 15.8 (HR 0.65; 95% CI, 0.48 to 0.89;P =.007 )
25 Phase III pivotal trial for MBC patients HER2 + Trial Drugs Control Line Primary Endpoint CLEOPATRA Swain EMILIA Verma EGF30008 Geyer Results (months) Doce+trast+pert Doce+trast 1st PFS 18.5 vs 12.8 (HR 0.62; 95% CI, ; P <.001) Letro+palbo Cape+trast 2nd PFS 9.6 vs 6.4 (HR 0.65; 95% CI, ; P<.001) cape+lapatinib Cape 2nd TTP 5.4 vs 4.2 (HR 0.72; 95% CI, ; P =.008) EGF30008 Johnston PERTAIN Arpino Letro+lapatinib Letro 1st PFS 8.2 vs 3.0 (HR 0.71; 95% CI, ; P =.019) Ai+trast+pert Ai+trast 1st PFS 18.9 vs 15.8 (HR 0.65; 95% CI, 0.48 to 0.89;P =.007 )
26 progression free survival TN HR positive HER2 positive Triple Negative PFS1 9,93 9,89 3,8 PFS2 4,3 6,4 2,3 PFS3 3,7 4,3 2,2 PFS ,3 Bonotto M, et al. Oncologist 2015
27 TN: substantial heterogeneity TN Luminal Androgen Receptor (LAR) 16% Basal-like 1 (BL1) 25% Basal-like 2 (BL2) Mesenchimal stem-like (MSL) 13% Mesenchymal like (M) 21% Immunomodulatory (IM) 25% Bareche Y. Ann Oncol 2018
28 TN: substantial heterogeneity TN
29 TN: substantial heterogeneity TN
30 TN: substantial heterogeneity TN
31 Metastatic Breast Cancer (MBC): subtypes AR? PDL1??? HR MBC HER2 PK3CA?? ki67
32 Department of Oncology, University Hospital of Udine, Italy
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