Herceptin for Early HER2 Breast Cancer Extends Overall Survival

[AlaskaDenise]

Note this is for HER2 positive cancers only.....(i.e., fast growing).
http://www.medpagetoday.com/Hematolo...Cancer/tb/4810


<TABLE cellSpacing=0 cellPadding=0 width=623 border=0><TBODY><TR><TD class=large_head2 vAlign=top>Herceptin for Early HER2 Breast Cancer Extends Overall Survival
</TD><TD width=8></TD></TR><TR><TD></TD><TD class=credit vAlign=top>By Crystal Phend, Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
January 05, 2007
</TD><TD width=8> </TD></TR><TR><TD></TD><TD></TD><TD width=8> </TD></TR><TR><TD></TD><TD class=text vAlign=top align=left bgColor=#edebe0>MedPage Today Action Points

• Explain to interested patients that this study is the first to find a survival advantage for Herceptin in the adjuvant setting for HER2-positive early breast cancer.
• Caution patients that longer follow-up will be needed to see if the survival advantage persists.

</TD><TD width=8> </TD></TR><TR><TD></TD><TD class=text>Review
LONDON, Jan. 5 -- For early-stage breast cancer that is HER2-positive, a year of adjuvant Herceptin (trastuzumab) significantly improves overall survival two years later without undue cardiotoxicity, researchers here said.<?XML:NAMESPACE PREFIX = O /><O:P></O:P>


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A year of Herceptin after anthracycline-containing chemotherapy improved overall survival by 2.7% among women in the HERA study, reported Ian Smith, M.D., of the Royal Marsden Hospital, and colleagues, in the Jan. 6 issue of The Lancet.<O:P></O:P>
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"The emergence of this benefit after only two years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer," they wrote.<O:P></O:P>

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They added, "That the risk of cardiotoxicity remains low is encouraging." <O:P></O:P>
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Herceptin, a humanized monoclonal antibody against HER2, has previously been shown in the open-label HERA trial and others to improve disease free survival for women with HER2-positive early breast cancer after standard neoadjuvant or adjuvant chemotherapy.<O:P></O:P>

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While widespread adjuvant use ensued, "this use has been criticized by some because the findings arise from interim analyses, follow-up is short, and significant overall survival benefit has not been shown in any stand alone trial," Dr. Smith and coauthors wrote.<O:P></O:P>

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To see the effect on the secondary endpoint of overall survival advantage in the HERA trial, the researchers analyzed intent-to-treat data from 1,703 women who received Herceptin for one year and 1,698 in the control group.
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All participants had HER2-positive node positive or high-risk node negative breast cancer. Herceptin was given as an 8 mg/kg intravenous loading dose then 6 mg/kg every three weeks.
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After a median follow-up of about two years, 59 women in the treatment group and 90 in the placebo group had died (difference 1.8%, 3.5% versus 5.3%). The unadjusted hazard ratio for death in the Herceptin group compared with placebo was 0.66 (95% CI 0.47 to 0.91, P=0.0115). The absolute overall survival benefit was 2.7% (92.4% versus 89.7%) at three years after randomization.<O:P></O:P>

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Dr. Smith and colleagues said such survival findings after only two years are unusual among breast cancer treatment trials for any therapy.<O:P></O:P>

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"That this survival difference will not be sustained with further follow-up is a possibility," they wrote, though they calculated that the chance of losing significance with longer follow-up was less than 20%.<O:P></O:P>

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There were 218 disease-free survival events with Herceptin compared with 321 in the control group. The unadjusted hazard ratio for the risk of an event with Herceptin versus placebo was 0.64 (95% CI 0.54 to 0.76, P<0.0001).<O:P></O:P>

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This corresponded to an absolute disease-free survival benefit of 6.3% (80.6% versus 74.3%) at three years after randomization.<O:P></O:P>

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In an analysis censored for patients who switched over from the placebo group, the hazard ratio for overall survival benefit was 0.63 (95% CI 0.45 to 0.87, P=0.0051) and 0.63 for disease-free survival (95% CI 0.53 to 0.75, P<0.0001).<O:P></O:P>
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There were also fewer distant metastases among patients in the Herceptin group (9% versus 14%). The time to distant recurrence was significantly longer among the Herceptin group as well (HR 0.60, 95% CI 0.49 to 0.73, P<0.0001) for an absolute benefit of 6.3% at three years after randomization (85.7% versus 79.4%, P<0.0001).<O:P></O:P>

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Since both anthracycline-containing chemotherapy regimens and Herceptin are known to cause cardiotoxicity, women in the study had to have a left ventricular ejection fraction (LVEF) of at least 55% after chemotherapy and radiotherapy.
Those with congestive cardiac failure or other major cardiac problems were also excluded.<O:P></O:P>

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Still, some cardiac problems were seen in the study. The findings were:<O:P></O:P>
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• Severe congestive heart failure occurred among 10 women in the Herceptin group (0.6%) but none in the placebo group (P<0.0001). <O:P></O:P>
• Symptomatic congestive heart failure was likewise significantly more common among Herceptin patients (2% versus 0.1%, P<0.0001).<O:P></O:P>
• Confirmed significant LVEF drop was also more common with Herceptin (3% versus 0.5%, P<0.0001). <O:P></O:P>
• Four percent of patients discontinued Herceptin due to cardiac toxicity. <O:P></O:P>
• No cardiac deaths occurred in the Herceptin group though one did in the placebo group.<O:P></O:P>

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Overall, there were significantly more grade 3 or 4 adverse events in the Herceptin group with 11% versus 6% experiencing at least one (P<0.0001). Serious adverse events were also more common (9% versus 7%, respectively, P=0.0103). A nonsignificant increase was also seen for fatal adverse events (0.5% versus 0.2%, P=0.1601) though none seemed to have been caused by Herceptin.
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In an accompanying editorial, Daniel Hind, Ph.D., of the University of Sheffield in England, and colleagues, noted the data show that the addition of Herceptin reduced the absolute risk of death by 1.8% over two years and, at that stage, one extra woman will be alive for every 55 treated. "However, an eighth of women randomized to Herceptin died or relapsed over an average of two years."<O:P></O:P>

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They cautioned that there are still important questions remaining about longer-term benefit and, particularly, adverse cardiac effects.<O:P></O:P>

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"While there is cause for concern, perspective is needed: over two years, the risk of cardiac damage seems trivial compared with that of breast cancer recurrence," Dr. Hind and colleagues wrote. "Unless catastrophic long-term side-effects emerge for trastuzumab, HERA is good news for women with HER2-positive early breast cancer and adequate cardiac function."<O:P></O:P>
<O:P></O:P><TABLE cellSpacing=0 bgColor=#a0d7f6 border=1 hspace="1"><TBODY><TR><TD>The trial was sponsored and funded by Roche. Many of the researchers in the trial declared conflicts of interests with Roche. Other conflicts among the authors were for Sanofi Aventis, Bristol-Myers Squibb, AstraZeneca, Novartis, Pfizer, Lilly, Amgen, Genetech, and GlaxoSmithKline. Dr. Hind and the editorial authors declared no conflicts of interest.</TD></TR></TBODY></TABLE><O:P></O:P>
Primary source: The Lancet
Source reference:
Smith I, et al "Two-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomized controlled trial" Lancet 2007; 369: 29-36.

Additional source: The Lancet
Source reference:
Hind D, et al "Questions about adjuvant trastuzumab still remain" Lancet 2007; 369: 3-5. </TD></TR></TBODY></TABLE>

[Jonesie]

Re: Herceptin for Early HER2 Breast Cancer Extends Overall Survival

A neighbor of mine, 28 years old, just had cancer of the brain return after 3 years.
She is on radiation treatment daily for the next 6 weeks.
Is this something of benefit to her, or is there another treatment that may benefit her...in addition to the radiation?
She is tired, feels cold, and nauseated now.
She is a very pretty and nice young lady. She works in the medical profession.
Everyone here is very upset now.
Thanks

[AlaskaDenise]

Re: Herceptin for Early HER2 Breast Cancer Extends Overall Survival

Hereptin in not new, so I'd assume her oncologist would be using it if necessary.

From all I've read the Herceptin, it applies to breast cancer. It can however mentasticize to the brain, in which case it might apply - but I think the oncologist would know if it could be used.

Hope your friend does okay.

.

[Mingus]

Re: Herceptin for Early HER2 Breast Cancer Extends Overall Survival

The abstract of the clinical study from "The Lancet"

1: Lancet. 2007 Jan 6;369(9555):29-36. <SCRIPT language=JavaScript1.2><!--var PopUpMenu2_LocalConfig_jsmenu3Config = [ ["ShowCloseIcon","yes"], ["Help","window.open('/entrez/query/static/popup.html','Links_Help','resizable=no,scrollbars= yes,toolbar=no,location=no,directories=no,status=n o,menubar=no,copyhistory=no,alwaysRaised=no,depend =no,width=400,height=500');"], ["TitleText"," Links "]]var jsmenu3Config = [ ["UseLocalConfig","jsmenu3Config","",""]]//--></SCRIPT><SCRIPT language=JavaScript1.2><!--var Menu17208639 = [ ["UseLocalConfig","jsmenu3Config","",""], ["LinkOut","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubmed_AbstractPlus&cmd=Retrieve& db=pubmed&list_uids=17208639&dopt=ExternalLink'"," ",""]]//--></SCRIPT> Links
<DD class=abstract id=abstract17208639>2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial.

• Smith I,
• Procter M,
• Gelber RD,
• Guillaume S,
• Feyereislova A,
• Dowsett M,
• Goldhirsch A,
• Untch M,
• Mariani G,
• Baselga J,
• Kaufmann M,
• Cameron D,
• Bell R,
• Bergh J,
• Coleman R,
• Wardley A,
• Harbeck N,
• Lopez RI,
• Mallmann P,
• Gelmon K,
• Wilcken N,
• Wist E,
• Sanchez Rovira P,
• Piccart-Gebhart MJ;
• HERA study team.

Royal Marsden Hospital, London, UK. ian.smith@rmh.nhs.uk
BACKGROUND: Trastuzumab--a humanised monoclonal antibody against HER2--has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer. We investigated the drug's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study. METHODS: HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23.5 months (range 0-48 months). The primary endpoint of the trial was disease-free survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005-002385-11. FINDINGS: 97 (5.7%) patients randomised to observation alone and 58 (3.4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0.66 (95% CI 0.47-0.91; p=0.0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 (0.54-0.76; p<0.0001). INTERPRETATION: Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years. The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.
PMID: 17208639 [PubMed - in process]
</DD>