HER2 Support Group Forums - View Single Post - NeuVax bc vaccine effective in patients with low Her2 levels

dlaxague · 04-16-2008, 09:42 AM

Hi Cynthia,

I've tried to find good information about this study and it's not easy (smile). If it's available on the AACR website, I can't find it.

But one report does say that the "low expressing" cancers had a FISH ratio of <2. By current standards, that's HER2 negative.

>The control arm was also made up of all Her2 positive patients who received no vaccine.

No, I think that the control group had the two ranges of HER2 - "negative" as above, and positive. Just as the vaccine group did. I have an online acquaintance who was also in the trial and received the vaccine and she says she was told that she is HER2 negative.

I wonder what you'd see if you FISH tested all breast cancer. I wonder how many would be more than zero but less that 2. I wonder how many would be zero? Do we know these things? (not a rhetorical question - I am hoping that someone knows the answer).

And again, what's with the report of a 38% mortality rate for the nonvaccinated HER2 negative women? Math is not my strong point so correct me if I'm wrong, but that would be in the neighborhood of 17 deaths of the 44 members of the C-LE (no vaccine low expressor) group, in three years! I must be reading this wrong. Please help me out and correct me.

Debbie, attempting to copy/paste the info from BCN (which I think is the actual abstract rather than a press report of it) below. If that doesn't work I'll try to find a link.

AACR 2008: ABSTRACT #2545: Response to a preventive HER2/neu peptide (E75) vaccine based on HER2/neu status
[American Association for Cancer Research]
Background: HER2/neu is a source of immunogenic peptides and is over-expressed in 30% of early stage breast cancer (BCa) patients. We have conducted clinical trials with the HER2/neu E75-peptide vaccine in node-positive and node-negative BCa patients demonstrating all levels of HER2/neu expression.
Methods: A subset analysis review was performed of 165 BCa patients enrolled in our E75 vaccine trial based on the level of HER2/neu expression. Patients were HLA typed; HLA-A2+/A3+ patients were vaccinated (V); HLA-A2-/A3- patients served as controls (C). HER2/neu over-expressers (OE) were defined as FISH >2.0 and IHC 3+ HER2/neu tumors. Low-expressers (LE) included patients with IHC ranging from 0 to 2+. These 2 groups were assessed by clinicopathologic factors, immunologic response (in vivo DTH reactions and in vitro HLA-A2:IgG dimer assay) to the vaccine, and post-vaccine clinical responses (recurrence and survival).
Results: Of 165 patients assessed; 94 were vaccinated (30 OE = 32%, 64 LE = 68%) and 71 were controls (22 OE = 31%, 49 LE = 69%). HER2/neu over-expressers were similar regarding prognostic and treatment factors, except a statistically larger number of V-OE patients were hormone receptor negative (ER/PR-; p=0.02) and node-negative (p=0.007). Clinicopathologic factors were not significantly different between control and V-LE patients. Immunologic responses were similar as measured by DTH reactions (post DTH V-OE=12.7+1.9 vs. V-LE=15.1+1.8; p=0.6), but V-OE demonstrated a decreased number of E75-specific CD8+ T cells when compared to V-LE post-vaccination (V-OE vs. V-LE Dimer: 0.6+0.06% vs. 0.8+0.07%; p=0.08; V-OE vs. V-LE Max Dimer: 1.5+0.1% 1.9+0.1%; p=0.04). At 30 months median follow-up, disease recurrence rates (RR) were similar between V-OE and C-OE patients (V-OE vs. C-OE RR: 4.3% vs. 5.6%; p=0.7); however there was a 50% reduction in mortality rate (MR) among patients that recurred (V-OE vs. C-OE MR: 25% vs. 50%; p=NS). RR was reduced for vaccinated patients with low HER2/neu expression (V-LE vs. C-LE RR: 6.4% vs. 11.3%; p=0.3). Importantly, MR among those that recurred was 0% vs. 38% (p=0.2) for V-LE and C-LE BCa patients, respectively.
Conclusions: Patients with HER2/neu over-expressing breast cancer (FISH amplified (>2.0) and IHC 3+) respond well to the E75 vaccine immunologically and have a 50% absolute reduction in mortality compared to controls. Unexpectedly, patients with low-expressing (0 - 2+ on IHC) HER2/neu tumors show better response not only immunologically, but clinically with decreased breast cancer recurrence and 0% mortality following E75 peptide vaccination.

And again, these numbers were not significant.

04-16-2008, 09:42 AM	#8
dlaxague Senior Member Join Date: May 2006 Posts: 221	confusing abstracts and reports Hi Cynthia, I've tried to find good information about this study and it's not easy (smile). If it's available on the AACR website, I can't find it. But one report does say that the "low expressing" cancers had a FISH ratio of <2. By current standards, that's HER2 negative. >The control arm was also made up of all Her2 positive patients who received no vaccine. No, I think that the control group had the two ranges of HER2 - "negative" as above, and positive. Just as the vaccine group did. I have an online acquaintance who was also in the trial and received the vaccine and she says she was told that she is HER2 negative. I wonder what you'd see if you FISH tested all breast cancer. I wonder how many would be more than zero but less that 2. I wonder how many would be zero? Do we know these things? (not a rhetorical question - I am hoping that someone knows the answer). And again, what's with the report of a 38% mortality rate for the nonvaccinated HER2 negative women? Math is not my strong point so correct me if I'm wrong, but that would be in the neighborhood of 17 deaths of the 44 members of the C-LE (no vaccine low expressor) group, in three years! I must be reading this wrong. Please help me out and correct me. Debbie, attempting to copy/paste the info from BCN (which I think is the actual abstract rather than a press report of it) below. If that doesn't work I'll try to find a link. AACR 2008: ABSTRACT #2545: Response to a preventive HER2/neu peptide (E75) vaccine based on HER2/neu status [American Association for Cancer Research] Background: HER2/neu is a source of immunogenic peptides and is over-expressed in 30% of early stage breast cancer (BCa) patients. We have conducted clinical trials with the HER2/neu E75-peptide vaccine in node-positive and node-negative BCa patients demonstrating all levels of HER2/neu expression. Methods: A subset analysis review was performed of 165 BCa patients enrolled in our E75 vaccine trial based on the level of HER2/neu expression. Patients were HLA typed; HLA-A2+/A3+ patients were vaccinated (V); HLA-A2-/A3- patients served as controls (C). HER2/neu over-expressers (OE) were defined as FISH >2.0 and IHC 3+ HER2/neu tumors. Low-expressers (LE) included patients with IHC ranging from 0 to 2+. These 2 groups were assessed by clinicopathologic factors, immunologic response (in vivo DTH reactions and in vitro HLA-A2:IgG dimer assay) to the vaccine, and post-vaccine clinical responses (recurrence and survival). Results: Of 165 patients assessed; 94 were vaccinated (30 OE = 32%, 64 LE = 68%) and 71 were controls (22 OE = 31%, 49 LE = 69%). HER2/neu over-expressers were similar regarding prognostic and treatment factors, except a statistically larger number of V-OE patients were hormone receptor negative (ER/PR-; p=0.02) and node-negative (p=0.007). Clinicopathologic factors were not significantly different between control and V-LE patients. Immunologic responses were similar as measured by DTH reactions (post DTH V-OE=12.7+1.9 vs. V-LE=15.1+1.8; p=0.6), but V-OE demonstrated a decreased number of E75-specific CD8+ T cells when compared to V-LE post-vaccination (V-OE vs. V-LE Dimer: 0.6+0.06% vs. 0.8+0.07%; p=0.08; V-OE vs. V-LE Max Dimer: 1.5+0.1% 1.9+0.1%; p=0.04). At 30 months median follow-up, disease recurrence rates (RR) were similar between V-OE and C-OE patients (V-OE vs. C-OE RR: 4.3% vs. 5.6%; p=0.7); however there was a 50% reduction in mortality rate (MR) among patients that recurred (V-OE vs. C-OE MR: 25% vs. 50%; p=NS). RR was reduced for vaccinated patients with low HER2/neu expression (V-LE vs. C-LE RR: 6.4% vs. 11.3%; p=0.3). Importantly, MR among those that recurred was 0% vs. 38% (p=0.2) for V-LE and C-LE BCa patients, respectively. Conclusions: Patients with HER2/neu over-expressing breast cancer (FISH amplified (>2.0) and IHC 3+) respond well to the E75 vaccine immunologically and have a 50% absolute reduction in mortality compared to controls. Unexpectedly, patients with low-expressing (0 - 2+ on IHC) HER2/neu tumors show better response not only immunologically, but clinically with decreased breast cancer recurrence and 0% mortality following E75 peptide vaccination. And again, these numbers were not significant.