Update on Melanoma Treatment. Tara C Mitchell, MD

Size: px

Start display at page:

Download "Update on Melanoma Treatment. Tara C Mitchell, MD"

Noel Fowler
5 years ago
Views:

1 Update on Melanoma Treatment Tara C Mitchell, MD

2 Overview Immune therapy update Targeted therapy update New concepts in treating melanoma

3 What is the immune system? A complex network of protective cells Includes T cells, B cells, other important cells

4 A complex network of protective cells

5 How does anti-cancer immunity work?

6 Immune checkpoints slow down the immune response

7 New drugs block immune checkpoints Drugs block either PD-1 or CTLA-4 Allow normal T cell activation T cells can now kill tumor cells Anti-tumor effect can be LONG LASTING

8 Immune drugs block checkpoints, control cancer Pembrolizumab Nivolumab (new dosing) Ipilimumab

9 Growing list of approved immune therapy drugs 2011: Ipilimumab approved for melanoma 2014: Pembrolizumab approved 2014: Nivolumab approved 2015: 1 st combo approved (ipi/nivolumab) 2015: 1 st Oncolytic viral therapy approved Many promising treatments in clinical trials

10 Many more possibilities for immune checkpoint blockade

11 PD-1 blockade + Oncolytic viral therapy TVEC is the 1 st approved oncolytic viral therapy 1 Tumor cells Healthy cells 2 T-VEC GM-CSF TDA T-VEC Local effect Immature dendritic cell Mature dendritic cell TDA Systemic effect GM-CSF MHC CD80/ CD86 CD28 TDA TCR Cancer Immunity Cycle T cell 4 3 T cell Preliminary results: safe, effective with pembrolizumab

12 PD-1 blockade + IDO1 inhibitor: Was not effective in melanoma Epacadostat is an oral IDO1 inhibitor Safe when with pembrolizumab Large clinical trial did not show any benefit compared to pembrolizumab alone

13 Adoptive T cell therapy: TIL

14 Very early trials: CAR T cells

15 Can we stop treatment with immune therapy?

16 YES! Durable responses after stopping PD-1 blockade Robert JCO 2017

17 Patient population: Keynote patients achieved a complete response Patients could stop treatment if they: Received at least 6 months of treatment Confirmed complete response (2 scans) All but 4 patients remained in a complete response after stopping treatment (over 90%) Patients can regain a response with restarting

18 Stopping anti-pd-1 therapy Patients with a confirmed complete response can stop therapy with a long lasting response Patients with severe toxicity can also stop therapy and maintain a long lasting response

19 Dual checkpoint blockade: update Ipilimumab plus nivolumab together is also an approved 1 st line treatment option

20 Dual checkpoint blockade: Questions Good option for some patients Significant increase in toxicity Need better tests to see which patients will respond better to combination first versus PD- 1 blockade alone Ipilimumab can be reserved for 2 nd line treatment when PD-1 blockade doesn t work

21 Immune therapy related toxicity Common immune related side effects with PD-1 blockade: Itching/Rash Joint aches and pains Diarrhea Increased liver function tests Decreased thyroid funciton Uncommon events Kidney injury, lung inflammation, pancreatitis, neuropathies Patients are monitored closely for toxicity during treatment

22 Targeted therapy: BRAF activated melanoma Half of melanomas have activating BRAF mutations Leads to continuous activation of the cell cycle Ocular and mucosal melanomas have different mutations (KIT) Curtin NEJM 2005

23 Targeted therapy: BRAF activated melanoma Several approved BRAF targeted therapies: Dabrafenib and Trametenib Vemurafenb and Cobimetinib COMING SOON: Encorafenib and Binimetinib Curtin NEJM 2005

24 Early response to BRAF inhibition Flaherty NEJM 2010

25 Trials in progress: Combining BRAF and MEK inhibition BRAF inhibitors work quickly and in almost all patients with BRAF mutant melanoma Immune therapy works well and the response is long lasting Can we combine the two approaches? YES! Pembrolizumab plus dabrafenib plus trametinib clinical trial Atezolizumab plus vemurafenib plus cobimetinib clinical tria

26 Summary There has been much progress in the treatment options for advanced melanoma Ongoing clinical trials will lead to new advances We need better tests to determine who will benefit most from which treatments!

Evolving Treatment Strategies in the Management of Metastatic Melanoma: Novel Therapies for Improved Patient Outcomes. Disclosures

Evolving Treatment Strategies in the Management of Metastatic Melanoma: Novel Therapies for Improved Patient Outcomes Fall Managed Care Forum November 11, 2016 Matthew Taylor, M.D. Disclosures Consulting/Advisory