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!