ASCO 2016 - Anti-PD1/PDL1 combined with BRAFi in BRAF+ patients

Combining BRAF inhibitors with other treatments can sometimes lead to very unfortunate side effects, but remember what Weber noted (The words in red in the next section are his.): Atezolizumab (Tecentriq) combined with Vemurafenib

Vemurafenib Plus Atezolizumab in BRAF-Mutant Melanoma—Trial Design

Patients with untreated BRAFV600-mutant unresectable or metastatic melanoma (N = 17)  
Cohorts: 1- atezo and vemurafenib together   2- vemurafenib X 56 days followed by atezo
3- vemurafenib X 28 days  followed by Atezo.  Atezolizumab (an anti PD-L1 anti-body) was given IV q 3 wk at 20 or 15 mg/kg and Vemurafenib was BID at 960 mg during run in, then decreased to 720mg bid.
Confirmed overall response rate:  Cohort 1 - 33%, Cohort 2 - 75 %, Cohort 3 - 100%.  Overall 76% response rate.  Median of 12.2 months.  AE's were manageable with no grade 4.  Additive activity with excellent level of response.  You will hear much more about this combo in the future.

Now there is this from ASCO:

Responses in patients with BRAF V600-mutant metastatic melanoma receiving anti-PD1/PDL1 therapy alone or combined with BRAF inhibitors.  ASCO 2016. # 9546.  J Clin Oncol 34, 2016.  Barcena, Trinh, McIntyre, et al.

Background: Whether anti-PD1/PDL1 (anti-PD) therapy alone, or anti-PD combined with BRAF inhibitors (BRAFi) represents the best treatment for patients (pts) with BRAF V600-mutant metastatic melanoma (BMMM) remains unclear. Combination therapy has been attempted in practice to improve disease control in BMMM pts. We report our single-institution experience using anti-PD therapy both alone and in combination with BRAFi in BMMM. Methods: At MD Anderson Cancer Center, 457 metastatic melanoma pts (excluding uveal melanomas) received anti-PD therapy between November 2009 and December 2015. Among the 113 pts (25%) with BMMM, 34 (30%) pts were BRAFi-naïve and 79 (70%) were previously treated with BRAFi. These pts were separated into 4 cohorts based on exposure to BRAFi prior to anti-PD therapy (BRAFi naïve vs. treated) and whether anti-PD therapy was administered alone or in combination with BRAFi. Data were collected and analyzed for rates and duration of responses (RECIST v1.1) or disease stabilization. Results: See table. Conclusions: Our retrospective study showed anti-PD therapy alone had robust antitumor activity in pts with BMMM, regardless of prior BRAFi exposure.BRAFi-naïve pts appeared to achieve higher response rates with the combination of BRAFi and anti-PD therapy than with anti-PD therapy alone; however, the number of pts was small. BRAFi-treated pts derived less benefit from combined BRAFi and anti-PD therapy than from anti-PD alone.

	N (pts)	CRs+PRs N (%)	Median Response Duration mos (range)	SDs N (%)	Median Disease Control Duration mos (range)
BRAFi-naïve/anti-PD alone	14	5 (36)	25 (3+-34+)	7 (50)	5 (2+-7+)
BRAFi-naïve/anti-PD+BRAFi	20	10 (50)	9 (3-29+)	8 (40)	5 (2-10+)
BRAFi-treated/anti-PD alone	38	12 (32)	15 (7+-34+)	18 (47)	8 (3-18+)
BRAFi-treated/anti-PD+BRAFi	41	5 (12)	8 (7+-15+)	26 (63)	7 (2-16+)

All my best - c