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Liver & Lung Metastases Stephanie L. Graff, MD, FACP
Associate Director, Breast Cancer Research Program, Sarah Cannon Research Institute
National Breast Lead, Sarah Cannon Cancer Network
VISCERAL CRISIS
“Visceral crisis is defined as severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease. Visceral crisis is not the mere presence of visceral metastases but implies important visceral compromise leading to a clinical indication for a more rapidly efficacious therapy, particularly since another treatment option at progression will probably not be possible.”
–4TH International Consensus Conference for ABC
STATE OF LIVER & LUNG METASTASES
• Solitary lung mets will occur in 10-25% of mBC
• Liver mets occur in over half of mBC
• 5-12% mBC have isolated liver involvement
Local Therapy
LOCAL THERAPY FOR LUNG METS: SURGERY
• Resection of lung mets may be diagnostic • Ideal in patients with multiple good risk features:
solitary met, disease free interval >36 months, HR positive disease – No RCT—these patients may just have a good
outcome regardless – Retrospective case series suggest median survival 40-
100 months
J Natl Cancer Inst. 2010;102(7):456 Eur J Cardiothorac Surg. 2002;22(3):335.
LOCAL THERAPY FOR LUNG METS: RADIATION/LOCAL TECHNIQUES
• Radiofrequency Ablation (RFA):
– Electrode placed directly into tumor, grounded via pads to thigh, voltage is generated to heat tumor to >60 C
– Limited data specific to breast cancer mets
Int J Radiat Oncol Biol Phys. 2010;76(2):326 Int J Radiat Oncol Biol Phys. 2008;72(5):1516 .
LOCAL THERAPY FOR LUNG METS: RADIATION/LOCAL TECHNIQUES
• Stereotactic Body Radiation (SBRT), including Cyberknife®: – External beam radiation in very large doses of
radiation, defined as >6 Gy/fraction, given over few (five or fewer) fractions
– Small trial of 121 patient with 5 or fewer lung mets treated with SBRT had 4 year local control rates of 73%--some of those were breast cancer patients.
Int J Radiat Oncol Biol Phys. 2010;76(2):326 Int J Radiat Oncol Biol Phys. 2008;72(5):1516 .
LOCAL THERAPY OPTIONS FOR LIVER METS: SURGERY
• Liver resection can be diagnostic • Local resection may be appropriate in carefully selected
patients—asymptomatic patients with solitary mets, HR+ disease, long disease free interval – Half of patients thought to be good candidates will have
extensive disease at the time of laparotomy – Central vs. Peripheral disease – Retrospective review of 19 trials, 535 patients: mOS 40 months,
complication rate as high as 40%, mortality rate as high as 6%
Eur J Surg Oncol. 2000;26(3):209 Eur J Cancer. 2011 Oct;47(15):2282-90.
LOCAL THERAPY OPTIONS FOR LIVER METS: RADIATION/LOCAL TECHNIQUES
• Scant data around RFA and others (cryotherapy, TACE, etc)
• Small trial, 45 patients, solitary lesions < 3 cm: 90% had complete ablation, but 20% relapse at 8 months, 3yr OS 44%
.
Radiol Med. 2014;119(5):327
Systemic Therapy Sometimes location *DOES* matter
FALCON—HR+ Fulvestrant vs. aromatase inhibitor
Among the 208 patients with no visceral disease, median PFS with fulvestrant was 22.3 months, vs. 13.8 months (HR 0.59, P <.01). In contrast, among the 254 patients with visceral disease, the respective median PFS durations were 13.8 and 15.9 months (NS)
Tumor Response to Sacituzumab Govitecan
Local Response Evaluation by RECIST1.1
Objective response rate
CR
PR
31% (17/54)
0 17
Clinical benefit rate (CR+PR+SD ≥6 months)
48% (26/54)
• 63% (34/54) of patients with at least one CT response assessment had reduction of target lesions (sum of diameters)
-8 0
-6 0
-4 0
-2 0
0
2 0
4 0
Be
st
Re
sp
on
se
(% c
ha
ng
e i
n t
arg
et
les
ion
fro
m b
as
eli
ne
)
P a r t ia l re s p o n s e
S ta b le d is e a s e
P r o g r e s s io n
6 p ts w ith o u t C T a s s e s s m e n t a re n o t s h o w n
+ C o n tin u in g tre a tm e n t
+
+++
++
++
+
+
Median number of metastatic chemo lines: 2
Median number of prior metastatic lines: 5
Aditya Bardia
Contact: [email protected]
• 52 post-menopausal female with metastatic HR+ breast cancer and visceral mets
• Prior therapy with letrozole, palbociclib, exemestane, everolimus
Pretreatment On treatment
Target lesion size reduced
from 39x24.9 mm to
23.9x10mm
(Overall 37.2% reduction
per RECIST)
0
1
2
3
Pre-Treatment On-Treatment
TP53 (Y103fs)cfDNA
MAF
(%)
Clinical Response to Sacituzumab Govitecan
After 10 cycles
Aditya Bardia
Contact: [email protected]
• 36 pre-menopausal F with metastatic HR+ breast cancer and visceral mets
• Prior therapy with tamoxifen, letrozole+OFS, palbociclib, carboplatin, paclitaxel
Pretreatment On treatment
Target lesion size reduced
from 43.5x39.5 mm to
35.5x29.7mm
(Overall 28.1% reduction
per RECIST)
Pt currently on cycle 30
(May 2018)
Clinical Response to Sacituzumab Govitecan
After 14 cycles
Systemic Therapy Sometimes location *DOES NOT* matter
FDA Pooled Analysis: CDK4/6 Inhibitors in Less Common Subtypes, Gao et al
SOLAR-1 PFS IN PIK3CA MUTANT COHORT
35% reduction in risk of progression/death with alpelisib + fulvestrant in PIK3CA mutant cohort; no difference by visceral/non-visceral mets
Juric D et al SABCS 2018, GS3-8
Systemic Therapy Should metabolism and side effects matter?
Drug Metabolism
Liver safe Liver toxic/metabolized
cyclophosphamide capecitabine
gemcitabine doxorubicin
carboplatin taxanes (paclitaxel, docetaxel)
trastuzumab eribulin
fulvestrant CDK4/6 inhibitors
atezeolizumab everolimus
TDM-1
Management of Side Effects
• Fatigue • Taste changes • RUQ pain • Dyspnea • Post-thoracotomy syndrome • Hemoptysis • Nausea
Questions?
@DrSGraff
