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ESMO SUMMIT RUSSIA 2019Clinical case of treatment of metastatic triple negative breast cancerElena Glazkova
N.N. Blokhin’s National Medical Research Center of Oncology (Moscow)
10 june 2019 Kazan
CONFLICT OF INTEREST DISCLOSURE
Travel grants – Biocad, Pfizer
Patient E., 26 y.o. Jan 2015 – left breast skin redness, breast volume
enlargement, pain Mammography + US: skin edema, diffuse infiltration of
breast tissue without nodes, 13x12 mm and 13 mm left axillar lymph nodes, multiple left supraclavicular lymph nodes 8,5 mm.
Histology: infiltrative adenocarcinoma NST, G3, ER – 0, PR – 0, HER2 – 0, Ki67 – 85%
BRCA1/2 – wild type ECOG – 0 Premenopausal Hepatitis B, no viral load
NEOADJUVANT TREATMENTPatient E, 26 y.o.
29.04.15 - 5.08.15:Doxorubicin 40 mg/m2 – day 1Cisplatin 50 mg/m2 – day 1Paclitaxel 160 mg/m2 – day 1G-CSF (filgrastim) 5 mkg/kg – day 2-6
q2w, №8
Mammography + US (12.08.2015): partial response – residual skin edema, axillar lymph nodes disappeared, one supraclavicular lymph node – 5 mm (looks hyperplastic)
SURGICAL TREATMENT Patient E., 26 y.o.
27.08.15 – radical left mastectomyHistology: in breast tissue residual disease (60 mm) – invasive breast adenocarcinoma with grade 3 pathomorphological regression, 11/13 lymph nodes with invasive breast adenocarcinoma, grade 3 pathomorphological regression
RADIATION THERAPY Patient E., 26 y.o.• 26.10.15 started radiation therapy to the left chest wall and regional lymph
nodes• Neck lymph nodes enlargement is defined at start of radiation• Cytology confimed adenocarcinoma• 27.11.15 – 09.02.16 – chemotherapy concurrent with radiation:
Vinorelbine 25 mg/m2 d1,8 (4 cycles)• 09.12.2015 finished Radiation therapy (SRD 45 Gy +SIB (for left neck and
supraclavicular area) for 60 Gy.Toxicity: pulmonitis (after 4 cycles chemo), started prednisolone 1 mg/kg
• US (16.02.16) – regression neck lymph node – 3 mm• Chemotherapy stopped, treatment of pulmonitis (Feb-March)
QUESTIONS
• Reasons for concurrent chemoradiation in this case?• Surgical treatment for neck lymph node?• Other chemotherapeutical agents?
MAY 2016 Patient E., 27 y.o.
• US (10.05.16) – 2 left supraclavicular lymph nodes 10 &12 mm• Backpain• Scintigraphy of skeleton – suspicion L2 metastatic lesion• X-ray – L2 lytic lesion
WHAT CHEMOTHERAPEUTIC REGIMEN CHOOSE?Patient E., 27 y.o.
• Eribuline• Capecitabine• Ixabepilone + capecitabine• Gemcitabine + platinum salts• Immunotherapy
WHAT SAID ABC4 EXPERTS?
Cardoso F, Ann Oncol, 2018
WHAT ABOUT IMMUNOTERAPY?
Patient E., 27 y.o.
• May 2016 – started capecitabine (2000 mg/m2 d 1-14) + bisphosphonates
• Palliative radiation L1-4 SRD 20 Gy, SIB L2 SRD 9 Gy
US (11.07.16) – left supraclavicular lymph node 17 mm (before 10 &12 mm)
• Continuous capecitabine therapy + zoledronic acid• 18.08.16 – L2 vertebroplasty
US (29.08.16) – at left supraclavicular area creeping infiltration (15 mm) with nodes 5x5 & 8x6 mm, at lateral neck area nodes 7x4 mm – disease progression
Patient E., 27 y.o.
• September 2016 – starts 3rd line chemotherapy – eribuline• US after 2 cycles – partial response• 3rd line duration – 8 cycles• US 23.12.16 – disease progression, moderate neck pain• X-ray L2 – stable disease• December 2016 – started 4 line chemotherapy – cyclophosphamide
50 mg p.o. daily + methotrexate 5 mg p.o. twice week
FEBRUARY 2017Patient E., 28 y.o.
• US - at left supraclavicular and neck area creeping infiltration with multiple nodes 14x7 mm, 8x5 mm
• Severe neck pain• L2 lesion – stable disease• Started 5th line chemotherapy:gemcitabine 1000 mg/m2 d 1,8 + cisplatin 75 mg/m2 d1
• US after 2 cycles – disease stabilization • L2 lesion – partial regression• Neck pain regression• February – June 2017 6 cycles of chemo (disease
stabilization)
Toxicity: Nausea G2 - 3Vomiting G1No hematologic toxicity
WHAT IS THE BEST CHOICE IN THIS SITUATION?Patient E., 28 y.o.
• Continue chemotherapy• Change chemotherapy• Local treatment• Active surveillance
NECK CT SCAN 23.06.17Patient E., 28 y.o.
Patient E., 28 y.o.
• Since June 2017 – continued gemcitabine monotherapy• US after 2 cycles of chemo – disease progression, moderate pain• 2 cycles gemcitabine + cisplatin• US – disease stabilization. No effect on pain
Toxicity: Nausea G2 - 3Vomiting G1Neurotoxicity G2No hematologic toxicity
ANTIANDROGEN TREATMENT FOR BREAST CANCER CBR: 19% (5 of 26 pts with SD > 6 mos; no CR or PR)
Median 3 cycles of therapy (range: 2-57+); 2 pts remained on treatment after 57+ and 11+ cycles
Gucalp A, et al. Clin Cancer Res. 2013;19:5505-5512.
N = 26 (PFS events = 23)Median PFS: 12 wks (95% CI: 11-22)
Wks From Treatment Start0 12 24 36 48 60 72 84 204 216 228 240
100
80
60
40
20
0
DECEMBER 2017Patient E., 28 y.o.
• IHC reaction for AR positive (+++) in 98% of tumour cells• December 2017 started bicalutamide treatment, regress of pain• December 2017 – neurologic symptoms• Brain MRI – cystic tumor in left frontal lobe with area of contrast
enrichment• MRI control at January – tumor enlargement (18x15 mm) – brain
metastasis
JANUARY 2018Patient E., 29 y.o.
• Stereotactic radiation therapy for brain metastasis
• Continued bicalutamide treatment for 3 months
• February 2018 – lymph node enlargement, ulceration, severe pain
• ECOG1
WHAT IS THE BEST CHOISE IN THIS SITUATION?Patient E., 29 y.o.
• Continue bicalutamide treatment• Best supportive care• Chemotherapy• Clinical trials
FEBRUARY 2018Patient E., 29 y.o.
• Started 6 line chemotherapy – docetaxel• Treatment continued for 4 cycles with disease stabilization, pain
control• Toxicity – fatigue G2-3, arthralgia G2, myalgia G2, neurotoxicity G2• MSI- testing – MSI-H DNA phenotype• May 2018 – started nivolumab treatment 240 mg q2w
JUNE 2018Patient E., 29 y.o.
• After 2 nivolumab cycles – dispnoea G3, fever• X-ray – pulmonitis• ECOG3• Immediately started treatment with prednisolone 2 mg/kg• US – multiple liver metastases (up to 10 sm)• Symptomatic treatment• Patient died in June 2018
Treatment of metastatic TN BC for 32 month
THANK FOR YOUR ATTENTION!