Dr. Daud reviews ASCO 2016 - immunology updates for melanoma

Here is a link (not sure if you will be able to access it or not...you may have to log in via email, etc) to a review of ASCO 2016 presentations by Dr. Adil Daud, of San Francisco:  Primeoncology.org - 2016 Immunology oncology melanoma updates - Daud

As I mentioned when I did my review of ASCO abstracts in May and June, there was not much 'NEW' news....just confirmation of what previous studies were showing.  This review does not demonstrate much more than what we already know...but there are a few cool slides...for what it's worth:

Keynote - 001:  3 year overall survival (OS) in patients with advanced melanoma treated with Pembrolizumab (Keytruda)

• Most common immune related side effects in order of incidence were:  hypothyroidism, pneumonitis, colitis.
• No difference in OS between the 3 dosing arms (Pembro at 2mg/kg q 3wk, vs 10mg/kg q 3wk, vs 10mg/kg q 2 wks).
• Progression free survival (PFS) is better in the ipi naive patients.

Demonstrates complete responders and when they stopped taking pembro.

Median time to response = 3 months.

Median time to complete response = 13 months but some did not achieve complete response until 33 months.

If you've had a complete response, (and remember - these folks have STOPPED the med) your chance of a durable response is 97%.

 Keynote - 006:  Pembro vs Ipi

• OS with ipi @ 26 mo = 43%
• OS with pembro @ 26 mo = 55%
• PFS with ipi @ 26 mo = 14%
• PFS with pembro @ 26 mo = 30%
• However, if you are a responder to EITHER - the duration of response was about the same at 2 years.

Keynote - 006:  Pembro vs Ipi, efficacy by PD-L1 expression

• Treatment naive patients do best
• IF - you are PDL1 negative - you do better on ipi than if you're not (ie positive) in regard to PFS and OS.
• However, overall - anti-PD1 drugs still do better than ipi no matter if the patient if positive or negative for PD-L1.

Checkmate - 067:  Phase III ipi/nivo in treatment naive, advanced melanoma patients 

• 3 arms:  ipi/nivo or nivo alone or ipi alone
• ipi/nivo combo was best with ORR of 57%, followed by nivo at 44%, and ipi at 19%.
• BRAF mutant (BRAF positive) patients had a 67% ORR to the combo.  (NOTE:  Previously BRAF status had not been a proven factor in response rate.)

If you're PDL1 positive, nivo is as effective as the ipi/nivo combo when these numbers were examined statistically.

Checkmate - 064:  OS from randomized sequential nivo followed by ipi vs ipi followed by nivo.

I've had a cow and a rant...you name it...about this before:  2015: Sequential nivo then ipi = ORR of 41%. Ipi followed by nivo = ORR of 20%!!!! FDA! Are you listening???????
I really do hope that the FDA (and Dr. Flaherty) are paying attention!!! But...here you go:

Keynote - 029:  Pembro plus ipi - with ipi at only 1 mg/kg

• Bottom line - Just as effective as ipi/nivo combo where ipi is at 3 mg/kg, with fewer side effects. 

Masterkey 265:  Talimogene Laherparepvec (T-VEC) with pembro for unresectable Stage IIIB and IV melanoma patients

• T-VEC was given in injectable tumor and pembro was started via IV 5 weeks later.
• There were 21 patients.
• 6 patients had a complete response (all tumors were gone). 
• 8 patients had a partial response
• 70% of all injected LESIONS had a complete response
• 92% of injected lesions had a reduction
• 65% of NONinjected skin lesions got smaller
• 53% of NONinjected VISCERAL lesions got smaller

Dr. Daud's final points:  

Much love and appreciation to all the ratties!!! - c