I SOTTOGRUPPI FENOTIPICI E I RISULTATI SINORA RAGGIUNTI Marta Bonotto Department of Oncology, University Hospital of Udine, Italy
Breast Cancer
Metastatic Breast Cancer (MBC)
Metastatic Breast Cancer (MBC)
Metastatic Breast Cancer (MBC)
Metastatic Breast Cancer (MBC): subtypes HR MBC HER2
Metastatic Breast Cancer (MBC): subtypes HR + MBC TN HER2 +
Metastatic Breast Cancer (MBC): subtypes TN MBC HR + HER2 +
Metastatic Breast Cancer (MBC): subtypes Triple negative Luminal A Non Luminal HER2 Luminal HER2 Luminal B
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
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
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
Metastatic Breast Cancer (MBC): outcomes PFS1 PPS1 PFS2 PPS2 PFS n PPS n OS
OS estimation according to subtypes: REAL WORLD Luminal A Luminal B HER2 positive Triple negative Bonotto M. Oncologist 2014
Metastatic Breast Cancer (MBC): subtypes MBC HR + HER2 + Proliferation index? TN
OS estimation according to subtypes: REAL WORLD Luminal A Luminal B HER2 positive Triple negative Bonotto M. Oncologist 2014
Metastatic Breast Cancer (MBC): subtypes MBC HR + HER2 + Proliferation index?? TN
OS estimation according to subtypes: REAL WORLD Bonotto M. Oncologist 2014
REAL WORLD SCENARIO OS N Median (mo) Luminal A 88 45.3 Luminal B 138 29.7 HER2 positive 89 43.5 HER2 pos, ER and/or PgR pos 42 55.3 HER2 pos, ER and PgR neg 44 26 Triple Negative 44 10.2 No triple negative 315 35.7 PFS1 Luminal A 88 15.1 Luminal B 138 9.3 HER2 positive 89 10.0 HER2 pos, ER and/or PgR pos 42 17.5 HER2 pos, ER and PgR neg 44 8.1 Triple Negative 44 3.9 No triple negative 315 10.3 PPS1 Luminal A 88 24 Luminal B 138 18.9 HER2 positive 89 19 HER2 pos, ER and/or PgR pos 42 27.8 HER2 pos, ER and PgR neg 44 14 Triple Negative 44 6.1 No triple negative 315 19 Bonotto M. Oncologist 2014
Hypothetical scenarios for expected survival Seidman AD. J Clin Oncol 2018
REAL WORLD SCENARIO Bonotto M. Oncologist 2014
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 40503 Dickler Results (months) Exe+eve exe 2nd PFS 10.6 vs 4.1 (HR 0.36; 95% CI, 0.27-0.47; P <.001) Letro+palbo letro 1st PFS 24.8 vs 14.5 (HR 0.58; 95% CI, 0.46-0.72; P <.001) Fulv+palbo fulv 2nd PFS 9.5 vs 4.6 (HR 0.46; 95% CI, 0.36-0.59; P <.001) Letro+ribo letro 1st PFS 63% vs 43.3% (18-mo PFS) (HR 0.56; 95% CI, 0.43-0.72; P <.001) Fulv+abema fulv 2nd PFS 16.4 vs 9.3 (HR 0.55; 95% CI, 0.45-0.68; 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)
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 40503 Dickler Results (months) Exe+eve exe 2nd PFS 10.6 vs 4.1 (HR 0.36; 95% CI, 0.27-0.47; P <.001) Letro+palbo letro 1st PFS 24.8 vs 14.5 (HR 0.58; 95% CI, 0.46-0.72; P <.001) Fulv+palbo fulv 2nd PFS 9.5 vs 4.6 (HR 0.46; 95% CI, 0.36-0.59; P <.001) Letro+ribo letro 1st PFS 63% vs 43.3% (18-mo PFS) (HR 0.56; 95% CI, 0.43-0.72; P <.001) Fulv+abema fulv 2nd PFS 16.4 vs 9.3 (HR 0.55; 95% CI, 0.45-0.68; 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)
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, 0.51-0.75; P <.001) Letro+palbo Cape+trast 2nd PFS 9.6 vs 6.4 (HR 0.65; 95% CI, 0.55-0.77; P<.001) cape+lapatinib Cape 2nd TTP 5.4 vs 4.2 (HR 0.72; 95% CI, 0.56-0.92; P =.008) EGF30008 Johnston PERTAIN Arpino Letro+lapatinib Letro 1st PFS 8.2 vs 3.0 (HR 0.71; 95% CI, 0.53-0.96; 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 )
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, 0.51-0.75; P <.001) Letro+palbo Cape+trast 2nd PFS 9.6 vs 6.4 (HR 0.65; 95% CI, 0.55-0.77; P<.001) cape+lapatinib Cape 2nd TTP 5.4 vs 4.2 (HR 0.72; 95% CI, 0.56-0.92; P =.008) EGF30008 Johnston PERTAIN Arpino Letro+lapatinib Letro 1st PFS 8.2 vs 3.0 (HR 0.71; 95% CI, 0.53-0.96; 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 )
progression free survival TN 9.9 9.8 6.4 4.3 3.7 4.3 3 3 3.8 2.3 2.2 2.3 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 PFS4 3 3 2,3 Bonotto M, et al. Oncologist 2015
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
TN: substantial heterogeneity TN
TN: substantial heterogeneity TN
TN: substantial heterogeneity TN
Metastatic Breast Cancer (MBC): subtypes AR? PDL1??? HR MBC HER2 PK3CA?? ki67
marta.bonotto@asuiud.sanita.fvg.it Department of Oncology, University Hospital of Udine, Italy