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Mirco Pistelli Clinica di Oncologia Medica A. O. Ospedali ...
Transcript of Mirco Pistelli Clinica di Oncologia Medica A. O. Ospedali ...
NOVITA’ DAGLI STUDI DI TERAPIA ADIUVANTE PER IL
CARCINOMA MAMMARIO HER2+: RILEVANZA CLINICA
Mirco Pistelli Clinica di Oncologia Medica
A. O. Ospedali Riuniti Ancona
Perugia, 6 luglio 2018
Anti-HER2 adjuvant therapy: CHALLENGES WITH EVIDENCE
• Less chemotherapy (de-escalation)
• Duration of Trastuzumab: longer versus shorter
• Addition of other agents (escalation)
• ER+ HER2+
Impact of adjuvant trastuzumab on long-term outcome in early-stage HER2-positive breast cancer
1986-1992
2004-2008
Cossetti RJ et al JCO 2015
7178 pazienti- stadio I-III
Adjuvant Trastuzumab Trials: >13,000 Patients 2005 Was a Good Year
Anti-HER2 adjuvant therapy: CHALLENGES WITH EVIDENCE
• Less chemotherapy (de-escalation)
• Duration of Trastuzumab: longer versus shorter
• Addition of other agents (escalation)
• ER+ HER2+
Less chemotherapy: anthracyclines, yes or not?
Less chemotherapy: anthracyclines, yes or not?
Less chemotherapy: anthracyclines, yes or not?
Less chemotherapy: anthracyclines, yes or not?
Less chemotherapy: anthracyclines, yes or not?
Tolaney et al, NEJM 2015 & ASCO 2017
Less chemotherapy: anthracyclines, yes or not?
Less chemotherapy: anthracyclines, yes or not?
Tolaney et al, NEJM 2015 & ASCO 2017
Less chemotherapy: anthracyclines, yes or not?
Tolaney et al, NEJM 2015 & ASCO 2017
Less chemotherapy: anthracyclines, yes or not?
Tolaney et al, NEJM 2015 & ASCO 2017
Less chemotherapy: anthracyclines, yes or not?
Tolaney et al, NEJM 2015 & ASCO 2017
Adjuvant chemotherapy: yes or not?
Adjuvant chemotherapy is standard of care
Anti-HER2 adjuvant therapy: CHALLENGES WITH EVIDENCE
• Less chemotherapy (de-escalation)
• Duration of Trastuzumab: longer versus shorter
• Addition of other agents (escalation)
• ER+ HER2+
Just one year ago…
Just 7 months ago…
Just 1 month ago…
6 vs 12 months (DFS)
9 weeks vs 12 months (DFS)
HORG=481 pz
p=ns p=ns
PHARE=3380 pz
p=0.01
PERSEPHONE=4089 pz
Short-HER=1253 pz
p=ns
SOLD=2176 pz
p=ns
Short-HER=1253 pz PHARE=3380 pz PERSEPHONE=4089 pz
Subgroup analysis (DFS)
Slide 31
Presented By Martine Piccart-Gebhart at 2018 ASCO Annual Meeting
Anti-HER2 adjuvant therapy: CHALLENGES WITH EVIDENCE
• Less chemotherapy (de-escalation)
• Duration of Trastuzumab: longer versus shorter
• Addition of other agents (escalation)
• ER+ HER2+
Addition of other agents: Lapatinib
Martine Piccart, JCO 2016
Addition of other agents: Lapatinib
DFS L+T vs T=+2% (4y) p=ns OS L+T vs T=+1% (4y) p=ns
Addition of other agents: Neratinib
Martin M, Lancet Oncology 2017
Addition of other agents: Neratinib
DFS N+T vs T=+2.5% (5y) p=0.008
Martin M, Lancet Oncology 2017
Martin M, Lancet Oncology 2017
Addition of other agents: Neratinib
DFS N+T vs T=+4.4% (5y) p=0.002 DFS N+T vs T=+0.1% (5y) p=ns
Addition of other agents: Pertuzumab
(expected 89.2%)
Addition of other agents: Pertuzumab
* statistically signicant
ALTTO (N=8381) ExteNET (N=2840) APHINITY (N=4805)
T >2 cm 4199 (50.1%) 1401 (49.3%) 2879 (59.9%)
N+ (%) 4323 (51.6%) 2169 (76.4%) 3007 (62.6%)
DFS (control group) 86% (4y) 87.7% (5y) 90.6% (4y)
OS (control group) 94% (4y) nr nr
HR 0.84 0.73 0.81
in favour of «more» (ALL) +2% +2.5%* +1.7%*
in favour of «more» (ER+) +2% +4.4% * +1.4%
in favour of «more» (ER-) +3% +0.1% +2.3%
in favour of «more» (N0) nr Nr +0.5%
in favour of «more» (N+) nr nr** +3.2%*
** HR=0.67 (0.46-0.96) N>4
Addition of other agents: does it really benefit?
• Lapatinib: not approved for adjuvant treatment
• Neratinib: approved by FDA, rejected by EMA
• Pertuzumab: approved by FDA and EMA, waiting for AIFA.
Addition of other agents: where are we now?
Anti-HER2 adjuvant therapy: CHALLENGES WITH EVIDENCE
• Less chemotherapy (de-escalation)
• Duration of Trastuzumab: longer versus shorter
• Addition of other agents (escalation)
• ER+ HER2+
• We may (and probably are) over-treating a subgroup of ER+ HER2+ BC in the (neo-) adjuvant setting.
• Inhibition of HER2 without inhibition of ER may increase ER signaling allowing ER to act as an escape mechanism. This could contribute to the lower pCR seen in ER+HER2+ BC. Crosstalk could explain worse outcome in the ExteNET.
• There may be a subset of ER+HER2+ BC where ER inhibition is critical and more important than chemotherapy.
Why is this important?
• The use of Trastuzumab-based chemotherapy has dramatically improved outcome for patients with early stage HER2+ BC; patients in more recent trials have lower recurrence rates than in earlier trials.
• For the present, chemotherapy is a key component and standard of care for the treatment of early stage HER2+ BC.
• Further follow-up from APT trial demonstrates very favorable outcome with low rates of distant recurrence; thus can be considered for stage I HER2+ BC.
• A short duration of adjuvant Trastuzumab (< 12-mo) should be considered (especially if cardiac risk factors) and patients who cannot complete 12-mo can be reassured.
• Addition of pertuzumab to adjuvant regimens improves DFS but restricted to high risk patients (especially N+). However, don’t forget to select N+ HER2+ BC for neo-adjuvant treatment (pCR= ↑OS).
• ER+ HER2+ BC are heterogeneous and further therapeutic de-escalation could be evalueted.
Thoughts to take home