Sequential nivo then ipi = ORR of 41%. Ipi followed by nivo = ORR of 20%!!!! FDA! Are you listening???????

 As Weber alluded to in the webinar included in my last post...the synopsis thus far, of the CheckMate 064 trial with sequential Ipi followed by Nivo vs Nivo followed by Ipi was put out today at the 2015 European Cancer Congress.

BOTTOM LINE:  Folks who got nivo first followed by ipi had slightly more side effects (roughly 50 vs 43%) but they also had objective response rates of 41.2% vs only 20% in the ipi first group!!!!!!!!!!!!!!!!  Here's a link to an OncLive report:  Nivolumab before ipilimumab has greater efficacy, similar AEs

My thoughts:  Boy, do we ever owe the ratties in this one!  Not to mention, all the folks who took ipi first (with its higher side effect profile, response rate of 10-15%) instead of anti-PD1 (with its much lower side effect profile and response rate of 40-45%) because the FDA in all their wisdom said so!!!  So all those folks on some boards and one ridiculous onc in particular....telling folks, "Oh, don't worry your pretty little head about it....the effects will be additive...no matter the order."  Really, sir?  NOT!!!  No, I am not in a good mood.  I am not a happy girl.  I am rather brokenhearted.  I am so sorry for all of those who had to suffer and reap fewer benefits than the lucky few of us who got a go at it the other way round.  I realize that these results are not all gloom and doom.  The arm that got the ipi followed by nivo, still beat plain ipi response rates with the 20% they attained. One other thing to keep in mind that this data indicates thus far....is that the ipi/nivo COMBO, provides still better responses (58% vs 40%).  But....the way the FDA works, trials work, and pharma works...has me very upset at the moment.  However, the love and admiration I feel for the ratties is something I do not have the words to express.  God bless you everyone.  We are forever in your debt.  Much love and thanks, les

owed an objective response rate at 25 weeks of 41.2% among patients who received nivolumab first versus 20.0% in those who started treatment with ipilimumab. The unconfirmed response rates were 47.7% with nivolumab first and 22.6% with ipilimumab first. At 25 weeks, 38.2% of patients had progressed in the nivolumab-first arm versus 60% with ipilimumab-first group.
- See more at: http://www.onclive.com/conference-coverage/ecc-2015/nivolumab-before-ipilimumab-has-greater-efficacy-similar-aes#sthash.xCTrkmYZ.dpuf

showed an objective response rate at 25 weeks of 41.2% among patients who received nivolumab first versus 20.0% in those who started treatment with ipilimumab. The unconfirmed response rates were 47.7% with nivolumab first and 22.6% with ipilimumab first. At 25 weeks, 38.2% of patients had progressed in the nivolumab-first arm versus 60% with ipilimumab-first group.
- See more at: http://www.onclive.com/conference-coverage/ecc-2015/nivolumab-before-ipilimumab-has-greater-efficacy-similar-aes#sthash.xCTrkmYZ.dpuf

showed an objective response rate at 25 weeks of 41.2% among patients who received nivolumab first versus 20.0% in those who started treatment with ipilimumab. The unconfirmed response rates were 47.7% with nivolumab first and 22.6% with ipilimumab first. At 25 weeks, 38.2% of patients had progressed in the nivolumab-first arm versus 60% with ipilimumab-first group.
- See more at: http://www.onclive.com/conference-coverage/ecc-2015/nivolumab-before-ipilimumab-has-greater-efficacy-similar-aes#sthash.xCTrkmYZ.dpuf

Here's the abstract itself:

showed an objective response rate at 25 weeks of 41.2% among patients who received nivolumab first versus 20.0% in those who started treatment with ipilimumab. The unconfirmed response rates were 47.7% with nivolumab first and 22.6% with ipilimumab first. At 25 weeks, 38.2% of patients had progressed in the nivolumab-first arm versus 60% with ipilimumab-first group.
- See more at: http://www.onclive.com/conference-coverage/ecc-2015/nivolumab-before-ipilimumab-has-greater-efficacy-similar-aes#sthash.xCTrkmYZ.dpuf

 Abstract from European Cancer Congress 2015

An open-label, randomized, phase 2 study of nivolumab (NIVO) given sequentially with ipilimumab (IPI) in patients with advanced melanoma (CheckMate 064)

Speaker: F.S. Hodi (USA) [Hodi, Horak Weber, Ruisi, Slingluff, et al.]

Background: The results of a phase 3 study in advanced melanoma showed improved progression-free survival with the combination of NIVO at 1mg/kg and IPI at 3mg/kg vs. IPI alone, with an objective response rate (ORR) of 58% and grade 3/4 treatment-related adverse events (AEs) in 55% of patients (pts). The current phase 2 study evaluated the efficacy and safety of NIVO followed by IPI vs IPI followed by NIVO in advanced melanoma.

Materials and Methods: Eligible pts had unresectable stage III or IV melanoma, were treatment-naïve or had received one prior systemic therapy, had an ECOG performance status of 0 or 1, and were enrolled regardless of BRAF mutational status. Pts from 9 US sites (N=140) were randomized 1:1 to receive sequential induction treatment with NIVO 3mg/kg IV Q2W x 6 doses followed by IPI 3mg/kg IV Q3W x 4 doses (cohort A; N=68) or IPI 3mg/kg IV Q3W x 4 doses followed by NIVO 3mg/kg IV Q2W x 6 doses (cohort B; N=70). Following induction treatment, both cohorts received NIVO 3mg/kg IV Q2W until progression or unacceptable toxicity. The primary objective was to evaluate treatment-related grade 3–5 AEs during the induction periods.

Results: During the induction periods, treatment-related grade 3–5 AEs occurred in 50.0% and 42.9% of pts in cohorts A and B, respectively [Table]. Across study periods, the incidence of treatment-related grade 3/4 AEs was higher in cohort A. There were no study drug-related deaths in either cohort. By modified RECIST v1.1 (requiring confirmation at week 33), ORR at week 25 was 41.2% in cohort A vs. 20.0% in cohort B, with a lower progression rate in cohort A.

Conclusions: The results demonstrate improved efficacy outcomes with NIVO followed by IPI vs. IPI followed by NIVO in advanced melanoma, with a similar incidence of treatment-related AEs during the induction periods. The nature of AEs was similar to that previously observed with either agent, alone and in combination, whereas the frequency of AEs was consistent with previous reports for NIVO plus IPI. Further data from this study may inform the choice of treatment regimens in advanced melanoma.

Efficacy	Week 13		Week 25
	Cohort A (N=68)	Cohort B (N=70)	Cohort A (N=68)	Cohort B (N=70)
Complete response	0	0	0	0
Partial response, n (%)	24 (35.3)	7 (10.0)	28 (41.2)	14 (20.0)
Confirmed ORR, % (95%CI)*	−	−	41.2 (29.4,53.8)	20.0 (11.4,31.3)
Progression rate, % (95%CI)**	38.2 (26.7,50.8)	61.4 (49.0,72.8)	38.2 (26.7,50.8)	60.0 (47.6,71.5)