like Goldilocks&3bears, 12 months of herceptin seems...not too much, not too little..

[Lani]

just right

Lancet Oncol. 2013 Jun 10. pii: S1470-2045(13)70225-0. doi: 10.1016/S1470-2045(13)70225-0. [Epub ahead of print]
6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial.
Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Tubiana-Mathieu N, Cany L, Catala S, Khayat D, Pauporté I, Kramar A; the PHARE trial investigators.
Source
University Hospital J Minjoz, Besançon, France. Electronic address: xavier.pivot@univ-fcomte.fr.
Abstract
BACKGROUND:
Since 2005, 12 months of adjuvant trastuzumab has been the standard treatment for patients with HER2-positive early-stage breast cancer. However, the optimum duration of treatment has been debated. We did a non-inferiority trial of a shorter exposure of 6 months versus the standard 12 months of trastuzumab for patients with early breast cancer.
METHODS:
We did an open-label, randomised, phase 3 trial in 156 centres in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to 6 months of trastuzumab (administered by intravenous infusions over 30-90 min every 3 weeks; initial loading dose 8 mg/kg; 6 mg/kg thereafter) before randomisation were eligible. Patients were randomly assigned via central randomisation procedure with web-based software to continue trastuzumab for another 6 months (12 months total duration; control group) or to discontinue trastuzumab at 6 months (6 months total duration; experimental group). Randomisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy, oestrogen-receptor status, and centre using a minimisation algorithm. The primary endpoint was disease-free survival, with a prespecified non-inferiority margin of 1·15. Analyses were done in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00381901.
FINDINGS:
1691 patients were randomly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab; 1690 patients in each group were included in the intention-to-treat analyses. After a median follow-up of 42·5 months (IQR 30·1-51·6), 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group. 2-year disease-free survival was 93·8% (95% CI 92·6-94·9) in the 12-month group and 91·1% (89·7-92·4) in the 6-month group (hazard ratio 1·28, 95% CI 1·05-1·56; p=0·29). 119 (93%) of the 128 cardiac events (clinical or based on assessment of left ventricular ejection fraction) occurred while patients were receiving trastuzumab. Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group (96 [5·7%] of 1690 patients vs 32 [1·9%] of 1690 patients, p<0·0001).
INTERPRETATION:
After 3·5 years follow-up, we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab. Despite the higher rates of cardiac events, 12 months of adjuvant trastuzmab should remain the standard of care.
FUNDING:
French National Cancer Institute.
Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID: 23764181

[suzan w]

Good to know! I got it «just right»!!!!! Thanks for posting this, Lani!

[Becky]

But I wonder if more may be better - taking women to the 2 year mark.

For example, I started Herceptin late because it was not available and I got in the "no Herceptin" arm of the trial. My last chemo was Feb 1, 2005. Then in May, 2005, everything changed with the results of the 3 adjuvant Herceptin trials becoming public at the 2005 ASCO meeting in May. I quickly moved and got Herceptin alone starting in June 2005. In August 2005, I had my ovaries removed to be able to take Arimidex. This began in September 2005. There had been a trial (using metastatic women of which I am not) showing that the combo of Arimidex and Herceptin (only) for a year did wonders (plus being 50% ER positive but PR neg bodes better for an AI over Tamoxifen). So, to be on that combo for a year meant I would need a few more doses of Herceptin. And, ironically, if I could obtain 4 more (every three week) doses, not only did it put me at a full year on Arimidex/Herceptin but also brought me just beyond my 2 year mark. My oncologist agreed since the first 2 years is the highest risk of recurrence too. Somehow, my insurance allowed it so I ended up being on Herceptin for 16 months.

Just wondering. I know the Hera trial published 2 years of Herceptin results with the results that even though 2 years is slightly better, it was not statistically significant. And the Hera trial is different than the other trials as in Hera, Herceptin was given after Chemotherapy and not with chemo.

Who knows what the exact right thing is but I am nearing my 9 year mark and I am still here (and did not get Herceptin with my chemo but 4 months after chemo was done and 2 months after radiation was done).

[tricia keegan]

Thanks Lani and I was wondering that too Becky.

[sarah]

Interesting. Up until this study, tests had been showing that shorter was just as good. I'll be curious to learn what the hospital here does. Herceptin wasn't around for non-metatstic people the first time around for me and I asked about it several times but I did get it with the recurrence (metatastic) and had it for 6 years - had been told it would be for life at first. Like Becky, I'm now about 9 out from the recurrence.
Interestingly I saw my onc last week and he said that right now there is nothing available for NED people as a preventative but he seems to feel that this will come down the line sometime. Maybe the vaccine???

[vballmom]

Thanks for posting this. I had a Herceptin holiday due to a lowered EF, but my cardiologist monitoring me said I'm good to stay on. I was hoping to see that shorter was as good, but at least now there is a solid study to keep me even more motivated to stay on it for my year's worth of doses.