Disclosures None 1 NOT THE REAL QUESTION Did you get it all? Did - PDF document

Winship Cancer Institute of Emory University Is there a role for surgical resection for stage IV melanoma anymore? Debates and Didactics in Hematology ‐ Oncology Sea Island, GA August 9, 2014 Disclosures • None 1

NOT THE REAL QUESTION • Did you get it all? • Did my cancer come back? • Do I need a scan? • Am I cured? Single-agent therapy for melanoma Class Examples Response Rates Notes Alkylating agents Dacarbazine 10-20% Soft tissue, lung Nitrosoureas BCNU, CCNU, 10-20% Brain fotemustine Platinum Cisplatin, 10-20% Biochemotherapy compounds carboplatin Taxanes Paclitaxel, 10-20% docetaxel Imidazotetrazine Temozolomide 10-20% Brain IFN-  , IL-2 Biologics 10-20% Hormonal Tamoxifen 4-6% Dartmouth 2

Combination therapy for melanoma Name/Acronym Agents Response Rates Notes CVD Cisplatin, vinblastine, DTIC 24-45% Soft tissue, lung BOLD Bleomycin, Oncovin, lomustine, 4-40% Recent response rates 4-20% DTIC Dartmouth Cisplatin, BCNU, DTIC, tamoxifen 20-40% Tamoxifen probably does not enhance efficacy IFN-  +IL-2 IFN-  +IL-2 20-40% No clear improved efficacy over IL-2 alone IL-2+TIL IL-2+tumor infiltrating 20-38% Conditioning chemotherapy lymphocytes improves engraftment Bone marrow transplant Varies 20-81% Low CR rates, short duration of responses CVD+IL-2+IFN-  (BIO) alternated Alternating biochemotherapy 33% Similar response rate to CVD every 6 weeks alone Sequential biochemotherapy CVD+BIO immediately following 47-73% CVD->BIO appeared better than BIO->CVD Concurrent biochemotherapy CVD+BIO given together 63% Reduced treatment duration, more convenient, less toxic Canvaxin™ Trial 3

Surgery • Only therapy with predictable 100% response rate • Duration of response is variable • Selection is key Stage IV trial • Morton and colleagues • Surgery vs Best known medical therapy • Failed to accrue • Closed prematurely – Why? • Medical oncologists had preconceived notions about patients undergoing surgery 4

MSLT ‐ 1: Surgery +/ ‐ Systemic Rx Breakdown by “M” Stage Surgery vs Systemic Therapy 5

Interferon Ipilimumab 6

Trametinib (MEK Inhibition) Dabrafenib 7

Vemurafenib Anti ‐ PD 1 Therapy Antitumor Activity of Lambrolizumab. Hamid, et al. NEJM 2014 8

T ‐ Vec Stage IIIB/C Stage IV M1a/b Profiling (the good kind…) Class 1 10 ‐ yr MFS Class 1 = 84% Class 2 = 13% ROC = 0.8778 n=112 Accuracy = 79% p<0.0001 Sensitivity = 85% Class 2 9

Personalized Medicine • There are seven different drugs discussed in this presentation • All have shown some (questionable) benefit in the management of melanoma • It is a unique time in the care of these patients • There is no better time to pursue combination therapy than now Simple question: If you were a 47 year old patient with no significant medical comorbidities and two isolated small bowel metastases, what would you want? That remains the answer. 10

Winship Cancer Institute of Emory University Is there a role for surgical resection for stage IV melanoma anymore? 11