ESMO SUMMIT LATIN AMERICA 2019

Melanoma Clinical Cases

Ana Cláudia Galdino, MD

March, 2019

CONFLICT OF INTEREST DISCLOSURE

No conflict of interest

CASE 1

Male, 78 years old, ECOG PS 0 No allergies No comorbidities

2014 Diagnosis: Melanoma pT3a pN1b M0 in the right arm Management: Wide excision with safety margins and six-monthly follow up

CASE PRESENTATION CONT’D

2016 Recurrence as cutaneous metastasis Management: Resection only – BRAF WT; and six-monthly follow up

CASE PRESENTATION CONT’D

Oct/2017 Recurrence as brain and peri-pancreatic lymph nodes

CASE PRESENTATION CONT’D

Oct/2017 Recurrence as brain and peri-pancreatic lymph nodes

QUESTION FOR THE PANEL

How would you treat this patient?

a. SRS for brain metastasis, followed by anti-PD-1

b. Ipilimumab and anti-PD-1

c. Anti-PD-1 only

QUESTION FOR THE PANEL

How would you treat this patient?

a. SRS for brain metastasis, followed by anti-PD-1

b. Ipilimumab and anti-PD-1

c. Anti-PD-1 only

CASE PRESENTATION CONT’D

Nov/2017

Feb/2018

Nov/2017 SRS for brain metastasis, followed by anti-PD-1

CASE PRESENTATION CONT’D

Nov/2017

Feb/2018

CASE PRESENTATION CONT’D

Today Anti-PD-1 maintenance therapy

CASE 2

Male, 67 years old, ECOG PS 0 No allergies No comorbidities

Mar/2015 Due to dyspnea, clinical investigation revealed one suspected malignant lesion in

the right lower lobe. No primary tumor was found at that moment. Management: Right lower lobectomy Pathology report: Malignant Melanoma – BRAF V600E mutation Staging: PET/CT and Brain MRI – NED

Diagnosis: Metastatic Melanoma (lung) of unknown primary site – BRAF V600Emutation

Management: Three-monthly follow up

CASE PRESENTATION CONT’D

Jul/2016 PET/CT – No evidence of systemic disease

QUESTION FOR THE PANEL

How would you treat this patient?

a. Surgery + RT for surgical bed

b. BRAF/MEK inhibitors

c. BRAF/MEK inhibitors, followed by SRS for brain metastasis and then BRAF/MEKinhibitors

d. Ipilimumab and anti-PD-1, followed by anti-PD-1 only

QUESTION FOR THE PANEL

How would you treat this patient?

a. Surgery + RT for surgical bed

b. BRAF/MEK inhibitors

c. BRAF/MEK inhibitors, followed by SRS for brain metastasis and thenBRAF/MEK inhibitors

d. Ipilimumab and anti-PD-1, followed by anti-PD-1 only

CASE PRESENTATION CONT’D

Aug/17-21/2016 SRS for brain metastasis

CASE 3

Male, 64 years old, ECOG PS 0 No allergies No comorbidities

Jan/2015 Diagnosis: Melanoma pT4b pN0 M0 in the right leg Management: Wide excision + SNLB – 0/0

QUESTION FOR THE PANEL

How would you treat this patient? pT4b pN0

a. High-Dose Interferon

b. Low-Dose Interferon

c. Placebo-controlled trial for adjuvant therapy with PD1 or BRAF/MEK-I

d. Follow Up

QUESTION FOR THE PANEL

How would you treat this patient? pT4b pN0

a. High-Dose Interferon

b. Low-Dose Interferon

c. Placebo-controlled trial for adjuvant therapy with PD1 or BRAF/MEK-I

d. Follow Up - q 3 months for 2 years, and increasing intervals- CT Scan

CASE PRESENTATION CONT’D

Feb/2018 Recurrence as single site in right inguinal lymph node, between CT’s

QUESTION FOR THE PANEL

How would you treat this patient?

a. FNA – order BRAF to attempt neoadjuvant BRAF/MEK-I

b. FNA – to attempt neoadjuvant Ipi/Nivo

c. Nodal dissection and Adjuvant Therapy with anti PD1 (regardless of BRAF status)

d. Nodal dissection and Adjuvant Therapy with BRAF/MEK inhibitors if BRAF-mutated

QUESTION FOR THE PANEL

How would you treat this patient?

a. FNA – order BRAF to attempt neoadjuvant BRAF/MEK-I

b. FNA - to atempt neoadjuvant Ipi/Nivo

c. Nodal dissection and Adjuvant Therapy with anti PD1 (regardless of BRAFstatus)

d. Nodal dissection and Adjuvant Therapy with BRAF/MEK inhibitors if BRAF-mutated

CASE PRESENTATION CONT’D

Mar/2018 Nivolumab 3mg/kg q2w for three cycles and started with cough and fatigue SpO2

92% at rest

QUESTION FOR THE PANEL

Mar/2018

Diagnosis: Pneumonitis grade 2

Management: Nivolumab was interrupted and prednisone was started at 1mg/kg/dtaper during the next 30 days.

CASE PRESENTATION CONT’D

Abr/2018 Nivolumab 3mg/kg q2w is discontinued and prednisone 60mg PO is started

QUESTION FOR THE PANEL

How would you treat this patient?

a) Discontinue anti PD1 as adjuvant therapy

b) Resume Adjuvant Therapy with anti-PD1

c) Switch adjuvant therapy to BRAF/MEK - inhibitors

QUESTION FOR THE PANEL

How would you treat this patient?

a) Discontinue anti PD1 as adjuvant therapy

b) Resume Adjuvant Therapy with anti-PD1

c) Switch adjuvant therapy to BRAF/MEK - inhibitors

CASE 4

Female, 46 years old, ECOG PS 0 No allergies Comorbidities: hypothyroidism, bariatric surgery, hypertension

Jul/2018 Due to in the right axilla pain, she noted enlarged axillary lymph nodes. Normal

strength, but significant tingling USG revealed suspicious lymphadenopathy Incisional biopsy: Malignant Melanoma BRAF ordered Initial images identify only axillary lymph nodes with close contact with the right

brachial plexus

Diagnosis: Unresectable metastatic Melanoma (nodes) of unknown primary sitecTx cN3 M0 – BRAF ongoing

CASE PRESENTATION CONT’D

Jul/2018

QUESTION FOR THE PANEL

How would you treat this patient?

a. Wait for BRAF status (2 weeks, at least) and start neoadjuvant therapy withBRAF/MEK inhibitors

b. Neoadjuvant therapy with anti-PD1

c. Neoadjuvant therapy with Ipilimumab and Nivolumab

QUESTION FOR THE PANEL

How would you treat this patient?

a. Wait for BRAF status (2 weeks, ate least) and start neoadjuvant therapy withBRAF/MEK inhibitors

b. Neoadjuvant therapy with anti-PD1

c. Neoadjuvant therapy with Ipilimumab and Nivolumab

CASE PRESENTATION CONT’D

Aug2018 to Sep/2018 Ipilimumabe 3 + Nivolumabe 1 q3w for four cycles

CASE PRESENTATION CONT’D

Sep/2018 to date Nivolumabe 1 q3w for maintenance

QUESTION FOR THE PANEL

How would you treat this patient? - BRAF WT

a. Keep systemic therapy only (nivolumab, up to 2 years)

b. Surgery and discontinue systemic therapy

c. Surgery and adjuvant nivolumab, up to 2 years

QUESTION FOR THE PANEL

How would you treat this patient? - BRAF WT

a. Keep systemic therapy only (nivolumab, up to 2 years)

b. Surgery and discontinue systemic therapy

c. Surgery and adjuvant Nivolumabe, up to 2 years