for those following or participating in the E75 her2 vaccine trials at Walter Reed/PA

[Lani]

EDITED DUE TO "LOOPINESS" OF PROPELLERHEAD--

the 2008 version of the results are in and they are not as positive as the 2006 SABCS interim report--So read on with caution if you don't want to know...it's not really that bad, just that its not as good as the previous results and it seems the vaccine-induced immunity
waned with time(HOPEFULLY BOOSTER SHOTS WILL TAKE CARE OF THAT)

It's not all that bad, just that the significance of the difference in recurrence rates decreased as the trial matured further ie, as the vaccine recipients were further and further out from the time of vaccination. Still less patients in the vaccinated group recurred than in the control group (ALTHOUGH the "significance" of the difference in the recurrence results was lost, but not the "significance" in the pattern of recurrence.**

Glass half empty/glass half full--1)the immunity seems to wane with time, so they are now gearing up to give booster shots and hope this will help 2) the were unsure of the most efficacious dose/scheduling and perhaps the results will improve as more get a more efficacious dose 3) these are small numbers with larger trials perhaps more of the variables which caused these results will become clear 4) they are uncertain of the role of HLAB2/3 in this (a requirement to get into the vaccine arm of the trial) but think HLAB2 positivity itself may increase the rate of recurrence. Trial numbers with HLAB3+s are still small, but results initially seem similar.
they hope the results will improve with booster shots, more patients getting better doses, unravelling the relationship with HLA B3/4, b-- as time passes and the results are examined in more detail they will publish additional results.

An interesting finding is that those who recurred after vaccination recurred in sites other than "bone only" where as "bone only" was not an unusual site of recurrence for those receiving the vaccine. AGAIN, WITH additional time and greater numbers these results may change.

1: Clin Cancer Res. 2008 Feb 1;14(3):797-803.
Combined Clinical Trial Results of a HER2/neu (E75) Vaccine for the Prevention of Recurrence in High-Risk Breast Cancer Patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

Peoples GE, Holmes JP, Hueman MT, Mittendorf EA, Amin A, Khoo S, Dehqanzada ZA, Gurney JM, Woll MM, Ryan GB, Storrer CE, Craig D, Ioannides CG, Ponniah S.
Authors' Affiliations: Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas.
PURPOSE: E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients. EXPERIMENTAL DESIGN: E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented. RESULTS: One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted. CONCLUSIONS: E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.
PMID: 18245541 [PubMed - in process]



"Overall, the vaccinated patients were at higher risk for recurrence than the observed patients. More patients in the vaccine group were steroid hormone receptor negative and not on hormonal therapy. HLA-A2 has previously been implicated as a negative prognostic factor in ovarian (30) and prostate cancer (19, 31), and our results here extend this concept to breast cancer.

At our primary analysis, there was a statistically significant difference in recurrence rates between vaccinated and observed patients. However, this statistical finding did not extend out to 26 months due to additional recurrences, including a vaccine patient that recurred at 58 months. We have documented that E75 immunity wanes over time with only 48% of patients maintaining significant residual immunity at 6 months. As a result, a booster program has been initiated. Additionally, these are mixed trials with a total of seven different dose groups. Only one of the eight recurrent vaccinated patients received what is now determined to be the optimal biological dose of the vaccine. Interestingly, a difference in recurrence pattern was observed between the control and vaccine patients. Fifty percent of the observation patients had bone-only recurrences consistent with published rates (32–34), whereas no vaccine patients had bone-only recurrence. This surprising finding is being further investigated. Although there was a higher incidence of visceral metastases among vaccinated patients, the death rate was substantially lower, further suggesting a potential clinical benefit to the vaccine.

Although the E75 peptide has been exclusively tested in HLA-A2+ patients (50% of the population), additional data suggest that E75 binds HLA-A3+ (15% of the population; ref. 21). We extended the E75 vaccine to HLA-A3+ patients, and the toxicity profile, DTH reactions, and recurrence rates were similar to HLA-A2+ patients. This suggests expanded use of the E75 vaccine in HLA-A3+ patients, therefore addressing two-thirds of the general population with a single-peptide vaccine.

These data show that E75 is safe and effective at stimulating a HER2/neu-specific immune response and may prevent recurrence. These intriguing findings should be confirmed in a randomized, controlled phase III trial, enrolling only HLA-A2+ and HLA-A3+ patients."

**not sure this is good as "bone only" recurrence has better prognosis

[Cynthia]

Lani,

You state that, "It seemed more in the vaccinated group recurred than in the control group." I draw a different conclusion from the report.

At 20 months, 5.6% of vaccinated vs. 14.2 % of control group recurred.

At 26 months, 8.3% of vaccinated vs. 14.8% of control group recurred.

I note that these numbers reach statistical significance at 20 months, but not at 26 months, though the trend seems to hold that the recurrence rate among those who received the vaccine is roughly half of the rate of the control group. This was a phase I/II study, and they are about to roll out a phase III nationwide trial very soon, if they haven't done so already.

Full disclosure, I received this vaccine and have not recurred.

Best regards,