La malattia triplo negativa metastatica: quali trattamenti nella pratica clinica? - Roma, 27 Ottobre 2018 Relatore: Francesca Poggio - Aiom
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
2018 CARCINOMA MAMMARIO: I TRAGUARDI RAGGIUNTI E LE NUOVE SFIDE
La malattia triplo negativa metastatica:
quali trattamenti nella pratica clinica?
Roma, 27 Ottobre 2018
Relatore: Francesca Poggio
Disclosure Information
Relationship Relevant to this Session
Poggio, Francesca:
No relevant relationship to disclose.
Agenda • Introduction • Chemotherapy • PARPi • Immunotherapy • Endocrine therapy • Conclusions
Triple-Negative Breast Cancer (TNBC) • TNBC lacks expression of ER (
Triple-Negative Breast Cancer (TNBC) • Triple negative paradox aggressive clinical course, but high sensitivity to cytotoxic treatment • Patients with metastatic TNBC experience poor outcomes relative to patients with other breast cancer subtypes, with a median OS of ≈ 18 months or less Gobbini EJC 2018. Carey LA et al, Clin Cancer Res 2007.
The Heterogeneity of TNBC Subtype Gene expression profile Possible sensitivity Basal-like 1 high Ki-67; DNA damage response Platinum, PARPi Basal-like 2 GF pathways AntiEGFR Immuno-modulatory Immune genes Immunotherapy Mesenchymal Cell motility PIK3i Mesenchymal stem-like Cell motility; claudin-low Anti-angio Luminal androgen receptor Steroid pathways AR antagonist
Agenda • Introduction • Chemotherapy • PARPi • Immunotherapy • Endocrine therapy • Conclusions
Cardoso F et al, Ann Oncol 2018
Performance of CT in HER2-
Regimen Inv Ass PFS (m) ORR (%) Ref
(Measurable)
Robert,
Capecitabine 6.2 - JCO 2011
Miles,
Paclitaxel 9.1 - EJC 2017
Robert,
Tax/Anthra 8.2 - JCO 2011
Robert,
Cape + Beva 9.2 - JCO 2011
Welt,
Cape + Beva 8.8 - BCRT 2016
Brodowicz,
Cape + Beva (high risk) 8.3 30 BJC 2014
Brodowicz,
Cape + Beva (low risk) 11.5 28 BJC 2014
Miles,
Paclitaxel + Beva 11.2 - EJC 2017
Robert,
Tax/Anthra + Beva 10.3 - JCO 2011
Brodowicz,
Paclit + Beva (high risk) 11.1 46 BJC 2014
Brodowicz,
Paclit + Beva (low risk) 14.4 35 BJC 2014
Welt,
Cape+ Vinor + Beva 9.6 - BCRT 2016
Beva-based CT When the response is an end point
MonoCT with Carboplatin
TNT trial: study design
1:1
Tutt A, SABCS 2016.MonoCT with Carboplatin
TNT in unselected TNBC
mPFS
Carboplatin vs. Docetaxel
3.1 vs 4.4 months
(p=0.40)
ORR
Carboplatin vs. Docetaxel
31.4% vs 34.0%
(p=0.66)
Tutt A et al, Nature Medicine 2018MonoCT with Carboplatin
TNT in mBRCA
mPFS
Germline BRCA vs no germline
Carboplatin: 6.8 vs 2.9 months
Docetaxel: 4.4 vs 4.6 months
(p=0.002)
ORR
Germline BRCA vs no germline
Carboplatin: 68.0% vs 28.1%
Docetaxel: 33.3% vs 34.5%
(p=0.01)
Tutt A et al, Nature Medicine 2018PolyCT with Carboplatin
tnAcity trial
Yardley D et al, Ann Oncol 2018Eribulin beyond first-line in TNBC
• Pooled analysis:
• Study 301
• Eribulin
• TPC
• Study 305
• Eribulin
• Capecitabine
• 1644 patients
• eribulin: 946
• control: 698
• 352 TNBC
Pivot et al. Ann Oncol 2016Antibody drug coniugate
Sacituzumab Govitecan (IMMU-132)
The phase III trial ASCENT is ongoing…
Bardia et al, J Clin Oncol 2017Agenda • Introduction • Chemotherapy • PARPi • Immunotherapy • Endocrine therapy • Conclusions
BRCA and PARPi
OlimpyAD trial
302 MBC BRCA+:
• 205 olaparib
• 97 standard CT (capecitabine, vinorelbine, eribuline)
≤ 2 previous CT lines
About 75% with ≥ 2 mts sites
Median PFS: 7 vs 4 months
ORR 59.9 vs 28.8%
Robson M et al, N Engl J Med 2017.BRCA and PARPi
EMBRACA trial
431 MBC BRCA+:
• 287 talazoparib
• 144 standard CT
(cape, vino, eri)
≤ 3 previous CT lines
About 70% with visceral mts
Median PFS: 8.6 vs 5.6 months
ORR: 62.6 vs 27.2 %
Litton J et al, N Engl J Med 2018.BRCA and PARPi
PFS results
Poggio F et al, ESMO Open 2018.BRCA and PARPi
TNBC and platinum-naïve
Poggio F et al, ESMO Open 2018.Agenda • Introduction • Chemotherapy • PARPi • Immunotherapy • Endocrine therapy • Conclusions
Immunotherapy
PD-1 blockade: activity as single agent
Drug Phase Subtype PD-L1 N pts ORR
Pembrolizumab Ib TNBC ≥ 1% TC 32 18.5%
(anti-PD-1) PD-L1+ Stroma+
Ib ER+/HER2- ≥ 1% TC 25 12%
PD-L1+ Stroma+
II TNBC ≥1 CPS
1°line, PD-L1+ 52 23.1%
>1 line 170 4.7%
Atezolizumab Ia TNBC ≥5% IC 115 10%
(anti-PD-L1)
Avelumab Ib All ≥1% TC 168 3.0%
(anti-PD-L1) ≥5% TC
≥10%IC
TNBC 58 5.2%
ER+/HER2- 72 2.8%
Nanda R et al, J Clin Oncol 2016; Rugo H et al, SABCS 2015; Adams S et al, ASCO 2017; Schmid P et al, AACR 2017; Dirix YL et al, Breast Cancer Res and Treat 2017.Immunotherapy
Combination with chemotherapy: results
Drugs Phase Subtype Line of N pts ORR
treatment
Atezolizumab + Ib mTNBC 24 42%
nab-Paclitaxel 1 9 67%
2 8 25%
≥3 7 29%
Pembrolizumab + Ib/II mTNBC 39 33.3%
Eribuline 1L 17 41.2%
2-3L 22 27.3%
Adams et al, ASCO 2016; Tolaney S et al, SABCS 2016Immunotherapy
IMpassion130: trial design
Schmid P, NEJM 2018IMpassion130: PFS results
ITT population
PD-L1 positive
Schmid P, NEJM 2018IMpassion130: OS results
ITT population
PD-L1 positive
Schmid P, NEJM 2018Immunotherapy Ongoing phase III trials
Agenda • Introduction • Chemotherapy • PARPi • Immunotherapy • Endocrine therapy • Conclusions
Endocrine therapy
Clinical evidence
Author N Drug CBR (%)
Gucalp 452 Bicalutamide 19
Traina 118 Enzalutamide 35
Bonnefoi 30 Abiraterone 20
Gucalp A, Clin Cancer Res 2013; Traina TA J Clin Oncol 2018; Bonnefoi H, Ann Oncol 2016.Endocrine therapy Ongoing studies
Agenda • Introduction • Chemotherapy • PARPi • Immunotherapy • Endocrine therapy • Conclusions
Conclusions
• Current standard treatment options for unselected TNBC
remains chemotherapeutic approaches
• In mTNBC, a platinum regimen may be considered,
especially in BRCA-associated
• Results of OLIMPYAD and EMBRACA lead to add single agent
PARPi in the therapeutic repertoire of BRCA-associated
breast cancers
• Combination of PD-L1 blockade and chemotherapy new
standard for metastatic TNBC patients? Further research is
needed to better select patients who are likely to benefitYou can also read
