HERA update at SA

[Rozebud]

Found this abstract from late last week. Trying to think back to stats, but doesn't the last line on this chart imply the 2 year results are better than the 1 year results?? Or how do we read that? (Go to the actual link to see the chart in readable form.)



http://www.abstracts2view.com/sabcs05/view.php?nu=SABCS05L_371

[11] Trastuzumab (H: Herceptin ) following adjuvant chemotherapy (CT) significantly improves disease-free survival (DFS) in early breast cancer (BC) with HER2 overexpression: the HERA Trial.


Background: The Breast International Group (BIG), in collaboration with Roche, conducted an international, multi-center, randomized, 3-arm trial to compare 1 year of 3 weekly H (8 mg/kg iv day 1; 6 mg/kg iv q 3 weeks thereafter) with observation and 2 years of 3 weekly H with observation in patients with HER2 overexpressing, node-negative (T size > 1 cm) or node-positive BC who had completed at least 4 cycles of an acceptable (neo)adjuvant chemotherapy (CT) regimen. Adjuvant endocrine therapy (mostly tamoxifen) also followed CT for patients with hormone receptor positive disease. Prior to randomization, eligibility criteria included central confirmation of HER2 overexpression (3+) or amplification (FISH+) and a baseline LVEF (echo or MUGA) > 55 % following CT.
Methods: 5090 patients were enrolled from 12/2001 to 4/2005 by 478 institutions from Europe, Canada, South Africa, Israel, the Asia Pacific Region, Japan, and Latin America: median age=49 yrs, node negative=32%, hormone receptor negative=49%, prior anthracyclines (A)=68%, prior A and taxanes=25%.
Results: At a median follow-up of 1 year, 475 events were observed in the database and triggered the first and only interim analysis. The Independent Data Monitoring Committee (IDMC) recommended release of the results for the 1 year H arm (1694 pts; 127 events) versus observation (1693 pts; 220 events), which were presented at ASCO 2005 (see table below). The 2 year H arm also improved DFS compared with observation (p<0.0001). H-treated patients had a higher incidence of NYHA class III-IV CHF (cardiologist confirmed) with LVEF drop at least 10 EF points from baseline to below 50%: 9 (0.5%) with H v. 0 without H. Cardiac deaths were rare: 0 with H v. 1 without H.
Discussion:One year H significantly improves outcome compared with observation. The trial continues to assess 2 years v 1 year of H, and monitor late side effects. Updated results and information on cardiac AEs will be presented.



HERA Study Results - ASCO, May 16, 2005




DFS*

RFS

DDFS**

OS

HR

0.54

0.50

0.51

0.76

95% CI

0.43 - 0.67

0.40 - 0.63

0.40 - 0.66

0.47 - 1.23

p-value

< 0.0001

< 0.0001

< 0.0001

0.26

events

127 v. 220

113 v. 209

98 v. 179

29 v. 37

2-year %

85.8% v. 77.4%

87.2% v. 78.6%

89.7% v. 81.8%

96.0% v. 95.1%



*includes local, regional, distant recurrences, contralateral BC, 2nd malignancies, death without prior event. ** includes distant recurrences, contralateral BC, 2nd malignancies.



Thursday, December 8, 2005 3:00 PM

General Session 2 (1:30 PM-3:30 PM)

This I think is the full links to the trials referred to.

The Lancet made comment on one or both of the trials as to lack of data. I looked for figures I could not find, but am no professional/

Here are links to the two Herceptin trials reported in the New England Journals.

http://content.nejm.org/cgi/content...ournalcode=nejm

http://content.nejm.org/cgi/content...ournalcode=nejm

They can be found free on the New England Journal of Medicine site searching for herceptin date October 20 2005 in case the links do not work.

RB

[Rozebud]

RB - I typed "herceptin October 20 2005" in the search area and no articles came up?

Any chance you could cut and paste them here? Thanks - Rose

[anne]

Hi Rose,

Thank you for posting this. I have been eagerly waiting for these results. But this is v. unclear if 2 yrs are better than 1. I think many women here want to extend the Herceptin and I wonder when the full results will be released.

Anne

[RobinP]

Hi Rosebud,

I too try to make sense of the studies using my nursing background and biostatistic courses. However, trying to make sense of that last 2 year column is difficult. If indeed they are comparing 1 year to 2 year, at this early date, it appears the two year had a slight DFS benifit. However, I thought the interm analysis for 2 years was not ready yet; I thought that would be out by this spring 2006 at the ASCO meetings.

Anyway, if you are trying to view the NEJM HERA and NCI adjuvant trails, you ought to order the OCt NEJM issue from their website. I have this journal and the breakdown with statistical charts, kaplan HR scores etc. is much more informative than the internet NEJM abstracts.

[Becky]

It read to me that they were saying the DFS was better with the 2yr Herceptin arm in comparison to the observation group (and not in comparison to the 1 yr arm).


Becky

[RobinP]

No, the observation group would not have done that well with DFS.

[Joe]

Actually, the HERA trials are still ongoing. Read the following exerpt from the study carefully.

Length of study
Recruitment for the HERA Trial began in December 2001 and was completed in 2004. Enrolment will continue until early 2005. The final analysis of study results will take place approximately two years after the final patient has been entered into the study (pre-defined as after the 951st event).

This means that the final analysis will not be available until sometime in 2007. We do have several important contacts with Roche-Switzerland, who have assured us last week in San Antonio that we will be provided with the final and any interim results as they are published.

Regards
Joe

[Rupali]

Trastuzumab significantly improves DFS in HER2-overexpressing, node-negative or node-positive breast cancer

By Claire Sowerbutt

December 09, 2005

Trastuzumab has been found to significantly improve disease-free survival (DFS) in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing, node-negative or node-positive breast cancer. This finding was presented as part of the interim analysis of the HERA study by Richard D. Gelber, PhD, with the Harvard School of Public Health in Boston, Massachusetts, during the 28th Annual San Antonio Breast Cancer Symposium.

HERA is a large, multinational, multicenter, randomized, 3-arm trial designed to assess the comparative efficacies of 1 or 2 years of adjuvant treatment with trastuzumab vs observation in patients with HER2 positive breast cancer. Participants must have undergone surgery and completed a minimum of 4 cycles of an acceptable (neo) adjuvant chemotherapy regimen.

The study enrolled 5000 patients over a 3-year period. The primary efficacy endpoint was DFS, with 1 interim efficacy analysis conducted this April after the required 475 events had been met. Approximately one half of the patients were younger than 50 years of age. Approximately 94% of patients received chemotherapy containing an anthracycline, and 25% received taxane plus anthracycline therapy. Dr. Gelber reported that there was a significant improvement in DFS for patients who received 1 year of trastuzumab compared with thos patients randomized to observation alone. DFS at 2 years was 85.8% for the trastuzumab cohort and 77.4% for the observation arm, equivalent to a 46% reduction in the risk of a disease event (hazard ratio, 0.54; 95% confidence interval: 0.43-0.67; P < .001).

“With respect to the types of events reported, it was primarily distant events that were reduced with trastuzumab, but we still have a problem with central nervous system relapses,” Dr. Gelber explained. Specifically, while distant events were reduced from 9.1% with observation to 5.0% with trastuzumab, the proportion of those events affecting the central nervous system was similar between the 2 groups.

Data were also presented on the annual hazard rates for the first 1.5 years of the study. These analyses show a 14% to 15% risk for recurrence in the observation group compared with a 7%-8% risk for recurrence with trastuzumab. Dr. Gelber explained that, according to their calculations, “even if beyond this point both treatment groups have exactly the same risk of recurrence, and we continue to follow them for at least another 4 years, there’s less than a 20% chance that the statistical significance in the HERA trial would disappear.” He concluded that “in terms of reducing the risk of early events, these results are solid.”

An increase in cardiac events was reported in the trastuzumab treatment arm, although most of these have been clinically manageable. Specifically, 10 patients in the trastuzumab group have suffered from congestive heart failure, compared with no patients in the observation arm (P < .01). However, no cardiac-related deaths have been reported in the trastuzumab group.

Reference

Hera Study Team. Trastuzumab (H: Herceptin) following adjuvant chemotherapy (CT) significantly improves disease-free survival (DFS) in early breast cancer (BC) with HER2 overexpression: the HERA Trial. Program and abstracts of the 28th Annual San Antonio Breast Cancer Symposium; December 8-11, 2005; San Antonio, Texas. Abstract 11.

I am sorry I should have rechecked the links. They must have moved. I will try and remember to do that. Links working 12/12/05 trials.

RB


http://content.nejm.org/cgi/content/...urcetype=HWCIT

http://content.nejm.org/cgi/content/...urcetype=HWCIT

[Rupali]

Hi Joe,

1.5 years of HERA trila are over so we should see some results in 2006 ASCO.

Regards,
Rupali

[Rozebud]

Thanks RP. Thanks Rupali. Thanks Joe.

Robin, I think you're probably right, it's 2 years of follow up on probably both the 1 and 2 year arms combined vs. the control group. Now looking at the Finnish study I'm wondering if less is more, so to speak.