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?
