Sunday, January 24, 2016

Nivo/Opdivo now first line for ALL melanoma patients! BRAF positive or negative! Alone or with ipi!

FDA expands Nivolumab as first line for V600 BRAF positive patients!

In 2014, Nivo was FDA approved for use in advanced melanoma after patients had failed ipi and if BRAF positive, the BRAF inhibitors as well. In November of 2015, it gained additional approval for use as a first line drug for melanoma patients!!  BUT only if you were BRAF V600 wild type!!!!  This, in spite of numerous studies demonstrating that the response to anti-PD1 (Nivo or Pembro, actually) was the same no matter BRAF status! Here's a link with the history of Nivo/Opdivo approvals!

Now!  Check out the link at the very top. FINALLY! In all its wisdom, the FDA has recognized the results of the Checkmate-067 study in which patients treated with the nivo/ipi combo had "a reduced risk of progression by 58% compared with ipi alone in patients with advanced melanoma" while nivo alone "reduced risk of progression by 43% vs ipi" and whose outcomes for Nivo's use as a single agent or in combination with ipi were similar NO MATTER the patient's BRAF status.

Basics of the study:  945 untreated unresectable melanoma patients.  They were treated with:  Nivo 3mg/kg q 2 wks (n=316).  Ipi 3mg/kg every 3 wks (315). Ipi/nivo combo with nivo at 1mg/kg with ipi at 3mg/kg every three wks for 4 doses followed by nivo at 3mg/kg alone q2wks (314).

At 9 months:  Median PFS = 11.5 mo for combo, 6.9 mo for nivo, 2.9 mo for ipi.

PD-L1 positive patients  - PFS of 14 mo for both nivo arms vs 3.9 mo with ipi only.
PD-L1 negative patients - combo was better than single agent - with PFS of 11.2 mo with combo vs 5.2 mo with nivo alone and 2.8 mo with ipi alone.

Overall response rate:  50% with combo.  40% for nivo alone.  14% for ipi alone.
Complete response rate:  8.9% for combo. 8.5% for nivo alone.  1.9% for ipi alone.
BRAF mutant melanoma:  For combo median PFS = 11.7 months.  For nivo alone PFS = 5.6 mo.  For ipi PFS = 4 months.
BRAF wild-type:  For combo median PFS = 11.2 months.  For nivo alone PFS = 7.9 mo.  For ipi PFS = 2.8 months.

Most common side effects were the usual players:  diarrhea, colitis, increased lipase and ALT/AST levels....all to a greater extent with the combo.

Then today in the UK  there was this: Opdivo approved for advanced melanoma in England and Wales (although it is still not approved for NSC lung cancer there, yet).

About bloody time!!!!  NOW!!!!  Let's get some more approvals for Stage III/IV NED folks, shall we?????
Big thanks to Eric for finding and sharing!!  He beat B on this one!!!  - c

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