CHECKMATE 067 update

Last weekend, we also got the 3 year- update on CHECKMATE 067

the Ipi vs Nivo vs Ipi+Nivo study- the one that we don't like as underpowered to show a difference between Ipi+Nivo vs Nivo as THAT of course would have been the real question:

After 3 years, patients alive

34% with Ipi
52% with Nivo
58% with Ipi +Nivo

Compared to the 2 year OS of (was presented at AACR by J. Larkin in spring 2017):

45% with Ipi
59% with Nivo
64% with Ipi+ Nivo

So you indeed see the flattening of the curve- remember: infliction point is around 3 years (that's when the curve bends towards the tail, so patients who reach this will in all likelihood STAY alive)

Important to note: patients WITH BRAF, so BRAF pos did BETTER than BRAF wild-type patients, in particular on the Ipi plus Nivo combo (that's especially for the likes of HAS in France!!!) and this is the highest survival rate we've seen in advanced Melanoma. EVER.

3-year rates of overall survival of BRAF pos:

37% Ipi
56% Nivo

BUT this tops it all:
68% Ipi+ Nivo

Report about it
http://www.medscape.com/viewarticle/885516…

Full NEJM paper:

http://www.nejm.org/doi/full/10.1056/NEJMoa1709684

Earlier papers about Checkmate 067:

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1504030

BRIM 8

BRIM8: A phase III, randomized, double-blind, placebo-controlled study of vemurafenib adjuvant therapy in patients with surgically resected, cutaneous BRAF-mutant melanoma at high risk for recurrence (NCT01667419).

Important results for a patients with a high risk of recurrence- so that is Stage 3- whose tumours carry the BRAF mutation.

Standard of care- wide resection and lymph node removal, sometimes Interferone.

Cohort 1

Stage IIC, IIIA, IIIB and 

Cohort 2

IIIC

who wants placebo on a trial today?

DFS primary endpoint

Cohort 1
median 24 placebo
40 Vemurafenib

Cohort 2
placebo 7.7
Vem 13.3

'Number of events were needed- WHAT?!'



At 1 year:

placebo 78.9%
Vem 58%

but 46.3 vs 47.45 at 2 years

BUT in Stage IIC-IIIB

Distant free survival

pic here 

sigh- pooled analysis even if specified.....only looks good because of the early stage patients (IIC- IIIB)

Side effects-

57% Grade 3-4 toxicity and one death

Overall- as seen previously in Stage 4, also pyrexia

Conclusion: provides OS benefit for IIC-IIIB but not IIIC where it only prolongates time till progression.

Background: Approximately 50% of melanomas carry a mutation in the BRAF gene. The oral BRAF inhibitor vemurafenib (VEM) has demonstrated meaningful clinical benefit in BRAFV600 mutation-positive, locally advanced/unresectable or metastatic melanoma. For patients (pts) with resected melanoma, interferon alfa-2b represents the only widely approved adjuvant therapy; however, its use is limited by a modest improvement in disease recurrence and a high incidence of severe adverse effects that lead to treatment discontinuation in up to a third of pts. BRIM8 is a phase III, international, multicenter, double-blind, randomized, placebo-controlled study designed to evaluate the safety and efficacy of VEM in pts with resected cutaneous melanoma at high risk (>50%) for recurrence (stage IIC and III disease). Methods: Pts aged ≥18 yrs with histologically confirmed stage IIC or III BRAFV600mutation-positive (by cobas testing) melanoma of cutaneous origin that has been completely resected are eligible. Pts without clinical or radiologic evidence of regional lymph node involvement must undergo sentinel lymph node biopsy, and those with evidence of regional or sentinel lymph node involvement must undergo complete regional lymphadenectomy. Pts with a history of systemic therapy for treatment or prevention of melanoma (including interferon alfa-2b) are ineligible. Two cohorts (C) will enroll ~ 725 pts: C1—500 pts with completely resected stage IIC, IIIA (one or more nodal metastasis >1 mm in diameter, per Rotterdam classification), or IIIB cutaneous melanoma; C2—225 pts with stage IIIC cutaneous melanoma. Pts will be randomized 1:1 to receive VEM (960 mg bid) or placebo for 52 weeks with randomization stratified by pathologic stage and region (C1) and by region (C2). Primary efficacy outcome measure is investigator-assessed disease-free survival. Secondary efficacy outcome measures include overall and distant metastasis-free survival. Safety, pharmacokinetic, and pt-reported outcomes will also be assessed. As of 13 Jan 2014, 179/196 sites are active and 154 pts have been randomized (C1: 89; C2: 65). Clinical trial information: NCT01667419.

Presidential Symposium 3

And the session that we all have been waiting for is about to start: adjuvant therapies in Melanoma- so for patients with Stage 3 Melanoma!

QuickStart workshop Friday 9.00- 10-00

QuickStart to Melanoma at ESMO for Melanoma advocates!

Program and registration here

MPNE principles

We are getting ready, also for the MPNE booth! The printed version of the MPNE principles arrived today! 

How not to miss anything

We have annotated interesting sessions for Melanoma and all things advocacy on our team-up calendar here. Make sure you don't miss the most important sessions! 

p.s. if you think...'this doesn't look too busy'....you are looking at the week before the congress....

It is time again!

This year's ESMO congress will take place in Madrid from 8th- 12th September.

We are expecting a number of important Melanoma updates, so please make sure you follow this blog and our MPNE forums!