" Our data strongly suggest that selected pts with HER2+ tumors may not need chemo"

[Lani]

TBCRC 006: A multicenter phase II study of neoadjuvant lapatinib and trastuzumab in patients with HER2-overexpressing breast cancer.


Sub-category:
HER2+

Category:
Breast Cancer - HER2/ER

Meeting:
2011 ASCO Annual Meeting

Abstract No:
505

Citation:
J Clin Oncol 29: 2011 (suppl; abstr 505)


Attend this session at the
ASCO Annual Meeting!
Session: Breast Cancer - HER2/ER

Type: Oral Abstract Session

Time: Sunday June 5, 9:00 AM to 12:00 PM

Location: McCormick Place Hall B1

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Author(s): J. C. N. Chang, I. A. Mayer, A. Forero-Torres, R. Nanda, M. P. Goetz, A. A. Rodriguez, A. C. Pavlick, T. Wang, S. G. Hilsenbeck, C. Gutierrez, R. Schiff, C. K. Osborne, M. F. Rimawi, on behalf of the Translational Breast Cancer Research Consortium; The Methodist Hospital Research Institute, Houston, TX; Vanderbilt-Ingram Cancer Center, Nashville, TN; University of Alabama at Birmingham, Birmingham, AL; The University of Chicago, Chicago, IL; Mayo Clinic College of Medicine, Rochester, MN; Baylor College of Medicine, Houston, TX


Abstract Disclosures


Abstract:

Background: We reported that inhibition of the HER2 pathway with lapatinib (L) and trastuzumab (T) to block all homo- and hetero-dimer signaling leads to rapid eradication of HER2-amplified human xenografts in mice. In this clinical trial, we sought to translate these findings to patients (pts) using the L+T regimen without chemotherapy. Methods: Women with HER2+ breast cancers (>3cm or >2cm with palpable lymph nodes) were eligible. Pts received weekly T (4 mg/kg loading then 2mg/kg) and daily L 1,000 mg for 12 weeks. ER+ pts also received letrozole (plus goserelin if premenopausal), to block ER/HER crosstalk. Biopsies were obtained at baseline and weeks 2, 8, and 12 (surgery). This stratified study (ER+, ER-) was designed to detect an increase in pathologic response rate (pRR; defined as pathologic complete response in the breast (pCR) plus residual disease that is <1 cm (npCR)) from 10% with T alone to 35% in each stratum, using a Simon optimal two stage design, with one-sided alpha=5% and power=85%. Both strata met criteria to continue to full accrual (at least 21 per stratum). Results: We enrolled 66 eligible pts; 64 were evaluable for response (Table). Median tumor size was 6 cm (range 1.5-30 cm). Adverse events (AEs) were overall modest: mainly grade 1-2 (GI: 64%, skin: 45%). Grade 3 metabolic, GI, and liver (18%, 12 pts) and grade 4 liver toxicity (1 pt) were also observed. Two pts had treatment related serious AEs (GI, liver). Efficacy results below are for the first 57 pts who had surgery as of 1/4/2011. Results from all pts will be presented at the meeting. Overall pRR was 53% (ER+: 55%, ER-: 47%). More importantly, the overall pCR rate was 28% (ER+: 21%, ER-: 42%). Conclusions: L+T for 12 weeks led to a high pCR rate in pts with large HER2+ tumors without chemotherapy. Pts with npCR might be converted to pCR with longer therapy, a hypothesis to be tested in a follow up study. Our data strongly suggest that selected pts with HER2+ tumors may not need chemotherapy.


N %
Menopausal status
Pre 32 48
Peri 4 6
Post 30 46
Age
≤50 35 53
>50 31 47
Race
White 48 73
Black 14 21
Other 4 6
Ethnicity
Hispanic 22 33
Not Hispanic 43 65
Tumor size
≤5 cm 24 39
>5 cm 38 61
Median 6 cm
ER
+ 41 62
- 25 38

[Hopeful]

Here is a link to an article that discusses this abstract:

http://www.redorbit.com/news/health/2050703/certain_breast_cancer_patients_may_benefit_from_co mbined_her2_targeted/index.html?source=r_health#

I did not have chemotherapy for my stage 1 bc in 2006; my onc offered me a course of Herceptin and AI's. In my most recent visit with him this week, he told me that he is still offering that protocol to his patients who decline chemotherapy. Don't know if he will be looking to add Tykerb to that regimen in the future based on Osborne's work.

Hopeful

[Jean]

Hopeful,
Thank you for the posting the article.
Great news ...now ...let's hope the subgroup that can have treatment without chemo will be discovered soon.
This is exciting news...I am sure that AA will be happy to hear that finally there are studies on pts. who can be treated w/o chemo.

News days are coming.
jean

[Becky]

Until they discover the biomarkers for the women this works for, I think the only way to try out this "no chemo" method is to have treatment prior to surgery (neoadjuvant) and see if the Herceptin/Tykerb melts your tumor (regards of size) away. Then you can have surgery and continue on Herceptin and/or Tykerb afterwards (plus rads if lumpectomy).

Its great news that this will be a future option for sure.

[AlaskaAngel]

I do hope so!

I hope they can use the info from this study eventually to go so far as to figure out IF there is a broad basis for HER bc and a more natural universal metabolic mechanism to control it, rather than using chemotherapy -- with a better understanding of the aging process and the hormonal metabolic influences.

AlaskaAngel

[Basilic]

I am on this trial. I started in mid-January and will be finishing off in 4 weeks. So far results have been great and side effects have been minimal to non-existent. When I began treatment, I had a >7 cm tumor and also had IBC. By the 2nd infusion, my tumor had shrunk to 1/2 its original size and the redness had substantially reduced. By week 12, the tumor could only be detected by mammogram and ultrasound and was merely 0.8 cm. The IBC identifyers (peau d'orange, adema, redness) are gone as well.

I'll be having surgery some time in the first week of July and hopefully the cancer will have cleared. I'll still have to do standard adjuvent chemo and more Herceptin after.

[Hopeful]

Those are some pretty dramatic results, Basilic! Thanks for sharing. Best of luck to you with your treatment plan.

Hopeful

[Basilic]

Hopefully all the others in the trial are responding as well. If so, this could eventually make a radical change in neoadjuvent and possibly adjuvent treatment for future her2 positive BC patients.

Wouldn't it be something if doctor's could then say, "if you have to have cancer than her2 is the one you want?" That's what they told me when I had DCIS (0) in 2004 in the other breast. At the time it was to small to be considered for her2 testing, but I was also ER/PR negative then as well.

[harrie]

Interesting article. My surgical oncologist, back in 2006, implied it may not necessarily be a bad idea to have the surgery, herceptin and AI and forgo the chemo. I did end up having the chemo also.
I wonder if it was ever considered to extract components of the tumor and see how it responds to the treatment as part of the evaluation for tx.
It's been so long since I ever visited the site, I had to "retrieve password". I was getting a little disgusted with all the scammers infiltrating.

[michka]

Happy to see you on the board Harrie and most of all that you are well! Michka

[harrie]

Hi Michka, thank you for the welcome. It is nice to hear from you again also.

[Basilic]

Update - Neoadjuvant treatment of Herceptin and Tykerb

I completed my Herceptin/Tykerb treatment at the end of June and had my surgery July 3rd. The cancer was not completely cleared as I had hoped but all that remained of that very large tumor (>7 cm) were two small nodules less than .8 cm each. I had 27 lymph nodes removed and only 4 of those still had cancer. It's difficult to depict how many lymph nodes were originally malignant from the MRI, but more than likely I had a lot more than 4 when I started. The important thing is that I had good clear margins. I start AC on August 16.

Overall, my reponse was great compared to where I started from.

Stage IIIb/with IBC
grade 3 tumor
negative ER/PR
> 7 cm
Her2++ (I think ratio was 11.8)

[suzan w]

When I had chemo in 2005, it was 'required' before herceptin treatments. My onc. questioned the need for chemo for me because of my statistics, and at that time she had to prescribe the herceptin "off label" because it was not yet approved for early stage BC. Times are changing rapidly thanks to research and test studies. I am so grateful to all of the participants in these studies, and the $$ for research that is making all of these remarkable advances in treatment. In 2005 when I was dx'd the first onc. told me basically that Her2 +++was a 'death sentence'. And just recently I read that early stage BC, Her2+++, treated with herceptin may be the first type of breast cancer that doctors can say is 'cured'. Never give up!!!

['lizbeth]

Love this study!

It truly shows the effectiveness of the Tykerb Herceptin combination. Now there are more options to put with it.

I can't wait to see studies come out with other targeted therapies.

Is there a study yet with TDM1 and Tykerb? Or Pertuzumaub, Herceptin and Tykerb?

I have been waiting for studies with neoadjuvant treatments with targeted therapies. I can't wait until the day when chemo, surgery and radiation fade into medical history . . . !

[AMOC1973]

Hi Basilic. I am also on the study. Im at Baylor. Started late July. I get my 4th dose of Herceptin next Tuesday. I'm receiving the tykerb/herceptin combo for 6 months. Did you receive the combo for 3 or 6 months? Your results are phenomenal. I hope I experience the same. My tumor has decreased in size to almost half so far. It was 6cm when measured by hand...I rather go by my MRI and say I started at 5cm :) I know I have one positive node. I'll finish the study end of December...then surgery, chemo, rads.

[Basilic]

I was wondering if I would run into anyone else on this study. I am also at BCM. I was selected for 24 weeks and unlike chemo, it got easier as time went along. I bought a big bottle of Imodium thinking I would be taking it on a regular basis but by the end of 6 months I had used less than a dozen.

The measurements from the MRI were 2cm larger than what was measured by hand.

[AMOC1973]

So far I've only had to use the Immodium once. I started probiotics twice a day...not sure if that's the reason I haven't experienced too much of GI side effects. Sounds like You had excellent results. And thats before chemo. Im not looking forward to chemo at all. But i wanna get this crap over with.
I've seemed to have the worst side effects from the femera & lupron. started getting hot flashes & they are awful. Can't sleep. Have tried neurontin (didn't work), Effexor (made me depressed). Just started clonidine 2 days ago....no help yet.
It's insane that 2 months ago I was feeling old cuz I was turning 39. What an idiot!!!

[Basilic]

I used the immodium more at the beginning because the study coordinator told me that I should take it as soon as I saw need. But then I wouldn't go for a couple days so decided to wait and see if I repeated loose stools before jumping on the imodium and then found I usually didn't need to take it.

I was ER/PR negative so didn't need hormone inhibitors. Right now I have trouble falling to sleep due to the prednisone they give me in a cocktail with antinausea meds before tarting the chemo.