Adjuvant and Neoadjuvant Therapy in Melanoma

R. Amaria, MD

Assistant Professor, Melanoma Medical Oncology

1/31/2015

• Adjuvant therapy: additional cancer treatment given after surgery is complete to lower the risk of the cancer returning

• Neoadjuvant therapy: treatment given as a first step to shrink a tumor before surgery is performed

Adjuvant Therapy for Stage III Disease

Surgery Adjuvant therapy

Ideal Adjuvant Therapy

• Effective in destroying microscopic deposits of melanoma that could potentially be present after surgery

• Has limited or easily manageable toxicity

FDA Approved Medical Adjuvant Therapy

• Interferon-α and Pegylated interferon

Clinical Trials for Adjuvant Therapy

• Vaccines• New immunotherapies-ipilimumab, anti PD-1 antibodies

Patients with Surgically Removed Stage IIIa-IIIc melanoma

Ipilimumab10mg/kg

Placebo

Placebo Ipilimumab

Median time to relapse

17 months 26 months

Median overall survival

Not statistically different

Not statistically different

Significant toxicity rate

2% 49%

Neoadjuvant Therapy for Stage III Disease and Limited Stage IV disease

Surgery Adjuvant therapyNeoadjuvant Therapy

Ideal Neoadjuvant Therapy

• Effective in shrinking down tumor rapidly• Has easily manageable or predictable toxicity profile• Facilitates understanding of mechanisms of

response to therapy

87yo man with stage IIIc BRAF Mutated Melanoma

November 2014 January 2015

BRAF/MEKInhibition

November 2014January 2015

2 cycles of biochemotherapy

60 year old man with locally advanced sinonasal melanoma

Patients with stage IIIB/IIIC or oligometastatic stage IV (<3 lesions), + BRAF mutation

Blood draw and tumor

biopsyPre-treatment

Neoadjuvant BRAF/MEK x 8

weeks

Blood draw and tumor

biopsyat surgery

Restaging CT scans every

3 months with blood draws

Arm AUpfront surgery

Arm BNeoadjuvantBRAFi/MEKI

Surgical resection

Restaging via CTs followed by

surgical resection

Scheduled within 0-4

weeks

On treatment biopsy / blood draw (arm B

only)

Adjuvant BRAF/MEK x

44 weeks

Standard of care adjuvant therapy

(interferon vs. observation)

Follow up

Neoadjuvant Therapy Clinical Trials

Follow up

Patients with

stage IIIB/IIIC or

oligometastatic

stage IV

(≤3 lesions)

Blood draw

and tumor

biopsy

Pre-treatment

Blood draw

and tumor

harvested

at surgery

Restaging

CT scans

every 12

weeks

n=20

n=20

Arm ANeoadjuvant Nivolumab(4 doses)

Surgery

On treatment

biopsy /

blood draw

(prior to

dose 2 and

dose 3)

Adjuvant

Nivolumab x 6

months

Arm BNeoadjuvant Ipilimumab

& Nivolumab(3 doses)

Surgery

Adjuvant

Nivolumab x 6

months

Follow up

Follow up

Neoadjuvant Therapy Clinical Trials

Adjuvant and Neoadjuvant Therapy Summary

• Adjuvant therapy is administered after surgery to lessen the risk of melanoma recurring– Interferon/Pegylated Interferon are FDA

approved options– Clinical trials are ongoing

• Neoadjuvant therapy is given to shrink tumor down before surgery– Multiple clinical trials are ongoing or planned

Thank you for your attention

Questions?