Slamon et al trial results: TH very effective and equivalent to TCH in Stage IV her2+

[Lani]

Multicenter Phase III Randomized Trial Comparing Docetaxel and Trastuzumab With Docetaxel, Carboplatin, and Trastuzumab As First-Line Chemotherapy for Patients With HER2-Gene-Amplified Metastatic Breast Cancer (BCIRG 007 Study): Two Highly Active Therapeutic Regimens

1. Vicente Valero,
2. John Forbes,
3. Mark D. Pegram,
4. Tadeusz Pienkowski,
5. Wolfgang Eiermann,
6. Gunter von Minckwitz,
7. Henri Roche,
8. Miguel Martin,
9. John Crown,
10. John R. Mackey,
11. Pierre Fumoleau,
12. Janusz Rolski,
13. Zrinka Mrsic-Krmpotic,
14. Agnieszka Jagiello-Gruszfeld,
15. Alessandro Riva,
16. Marc Buyse,
17. Henry Taupin,
18. Guido Sauter,
19. Michael F. Press and
20. Dennis J. Slamon

+ Author Affiliations

1.
From The University of Texas M. D. Anderson Cancer Center, Houston, TX; Australia New Zealand Breast Cancer Trials Group, University of Newcastle, Calvary Mater Hospital, Newcastle, NSW, Australia; University of California, Los Angeles; University of Southern California, Los Angeles, CA; Marie Sklodowska-Curie Memorial Cancer Center, Warsaw and Krakow; Niepubliczny Zaklad Opieki Zdrowotnej Onko-Med, Olsztyn, Poland; Red Cross Women's Hospital, Munich; University Women's Hospital, Frankfurt, Germany; Institut Claudius Regaud, Toulouse; Cancer International Research Group, Paris; Centre Georges Francois Leclerc, Dijon, France; Hospital Gregorio Marañon and Grupo Español de Investigación en Cáncer de Mama, Madrid, Spain; St. Vincent's University Hospital, Irish Clinical Oncology Research Group, Dublin, Ireland; University of Alberta Cross Cancer Institute, Edmonton, Alberta, Canada; University Hospital for Tumors, Zagreb, Croatia; International Drug Development Institute, Louvain-la-Neuve; I-BioStat Center for Statistics, Hasselt University, Hasselt, Belgium; and Institute of Pathology, University of Basel, Basel, Switzerland.

1. Corresponding author: Vicente Valero, MD, Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: vvalero@mdanderson.org.

Abstract

Purpose Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC.

Patients and Methods Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m2) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m2). Trastuzumab was given at 4 mg/kg loading dose followed by a 2 mg/kg dose once per week during chemotherapy, and then 6 mg/kg once every 3 weeks until progression.

Results Patient characteristics were balanced between groups. There was no significant difference between TH and TCH in terms of the primary end point, time to progression (medians of 11.1 and 10.4 months, respectively; hazard ratio, 0.914; 95% CI, 0.694 to 1.203; P = .57), response rate (72% for both groups), or overall survival (medians of 37.1 and 37.4 months, respectively; P = .99). Rates of grades 3 or 4 adverse effects for TH and TCH, respectively, were neutropenic-related complications, 29% and 23%; thrombocytopenia, 2% and 15%; anemia, 5% and 11%; sensory neuropathy, 3% and 0.8%; fatigue, 5% and 12%; peripheral edema, 3.8% and 1.5%; and diarrhea, 2% and 10%. Two patients given TCH died of sepsis, and one patient given TH experienced sudden cardiac death. Absolute left ventricular ejection fraction decline > 15% was seen in 5.5% of patients on the TH arm and 6.7% of patients on the TCH arm.

Conclusion Adding carboplatin did not enhance TH antitumor activity.TH (docetaxel, 100 mg/m2) and TCH (docetaxel, 75 mg/m2) demonstrated efficacy with acceptable toxicity in women with HER2-amplified MBC.
Footnotes

*

Written on behalf of the Breast Cancer International Research Group BCIRG 007 trial investigators.
*

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
*

Clinical trial information can be found for the following: NCT00047255.

[KDR]

(medians of 37.1 and 37.4 months, respectively; P = .99).

Thanks for posting. Are these the number of months we metastatic patients can expect to live, generally speaking?

[bmorr7]

Hi,

Our oncologist is recommending the TCH regimen. Does this study imply that the TH regimen would be preferred over TCH for Her-2 positive stage 1 breast cancer?

Thanks,

Ben

[Andrea Barnett Budin]

I only know TH -- and supplements -- have worked for me.

I wouldn't want to add more toxicity w/C.

Taxotere hit me hard. I didn't care. I wanted to live! I saw myself as being in a process and would walk through fire to get there. For me, Taxotere was hell. But I NEVER regret taking it, because I believe it contributed to me getting to STABLE. That was 1999. And I remain STABLE.

I did do 10 years of Vitamin H (what I affectionately call Herceptin). My onc thought 5 yrs would be enough. But I was not anxious to mess with success. If it isn't broken, why fix it???

I've been off for 5 yrs. Still STABLE...

[Jackie07]

Oncologist. 2013 Jun 28. [Epub ahead of print]
Health-Related Quality of Life With Adjuvant Docetaxel- and Trastuzumab-Based Regimens in Patients with Node-Positive and High-Risk Node-Negative, HER2-Positive Early Breast Cancer: Results from the BCIRG 006 Study.
Au HJ, Eiermann W, Robert NJ, Pienkowski T, Crown J, Martin M, Pawlicki M, Chan A, Mackey J, Glaspy J, Pintér T, Liu MC, Fornander T, Sehdev S, Ferrero JM, Bée V, Santana MJ, Miller DP, Lalla D, Slamon DJ; on behalf of the Translational Research In Oncology BCIRG 006 trial investigators.
Source
Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada;
Abstract
BACKGROUND:
This study aims to describe and compare health-related quality of life (HRQL) in patients with node-positive and high-risk node-negative HER2-positive early breast cancer receiving adjuvant docetaxel and trastuzumab-based or docetaxel-based regimens alone.
METHODS:
Eligible patients (n = 3,222) were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC→T) or one of two trastuzumab-containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year (AC→TH) or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year (TCH). The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and BR-23 were administered at baseline, the start of cycle 4 (mid), and the end of chemotherapy (EOC), as well as at 6, 12, and 24 months after chemotherapy.
RESULTS:
Compliance rates for the EORTC questionnaires were acceptable at 72%-93% of eligible patients out to the 12-month assessment. Systemic side effect (SE) change scores were significantly improved for TCH-treated patients compared with AC→TH and AC→T at EOC, suggesting improved tolerability. Physical functioning (PF) was only slightly worse at midpoint for those receiving TCH, compared with patients who were just starting on taxane in an AC→TH regimen, but was otherwise similar between arms. All treatment arms recovered from the deterioration in SE, PF, and Global Health Scale scores by 1 year and median future perspective change scores continued to improve throughout treatment and follow-up.
CONCLUSION:
HRQL outcomes for adjuvant docetaxel and trastuzumab-based regimens are favorable and support TCH as a more tolerable treatment option.

[Andrea Barnett Budin]

Jackie,

Hi! Trying to muddle my way through your post. Full of jargon that never fails to stymy me. However the last line I can read.

TCH is more tolerable (than TH)???

Am I reading that correctly?

['lizbeth]

The higher amount of Taxotere in the TH was too much for me. My nurse took pity and did a dose reduction to the TCH level for me, and it still didnt feel like this "doable" that everyone says. I'm starting to think everyone has a much more efficient liver than I.

KDR, I'm sorry but you won't be allowed to exit stage left in 10-11 months, we very much like having you as a fellow poster on the board. Remember Christine survived 20 years after having brain mets, and that was before all the additional treatments that are now available. So plan for the best as well as the worst!

Benjamin, honestly if I had to pick a treatment these days I'd enroll the ATEMPT trial and be randomized to TH or TDM1. You can also check out the I-Spy trial. This is, if your wife's BRCA test came back negative.

http://www.clinicaltrials.gov/ct2/show/NCT01853748

I had Taxotere, this study uses the other taxane Paclitaxel, which is similar.

I-SPY link:
http://www.clinicaltrials.gov/ct2/sh...y+stage&rank=8

With as concerned as you are, a clinical trial, which is expected to have effectiveness better than standard of care (TCH) might be a better decision. Keep in mind currently your wife is NED, no evidence of disease which means cancer free. So you can relax a little about making a choice. If you go with the most popular choice TCH - it still is a good decision. But she won't be doing anything to improve standard of care for others, nor will she receive the benefit of cutting edge research. And if the BRCA testing is positive, you must consider TCH and research platinum salts. Just my humble opinion.

Jackie, did you copy the wrong post? That compares ACTH to TCH, not TH to TCH.

[BonnieR]

Ben, this study seems to address Stage 4 metastatic cancer. These things can be very complicated and I suggest you discuss them with your oncologist. Great that you are doing your homework! Go in there armed with questions! You are a blessing to your wife.
Keep the faith

[Andrea Barnett Budin]

Benjamin -- Have you gotten independent 2nd opinion? Not from same office.

And possibly a 3rd opinion?

I found this to be the way to go. Each had something different to add to the mix. Each was brilliant, but saw things slightly differently.

Every hammer thinks you're a nail. Depending on their background, they each believe in their method. For me, the choices and my subsequent questions, led me to door #3. It felt right.

With Rachel being NED, you don't have to rush...

[BonnieR]

Andi makes a good point. You should always have more than one opinion. I got 3 all very different! The middle one did consider not including the Carboplatin because its the "roughest" of the mix but that was not the standard then. So I did all 3
Keep the faith

[bmorr7]

We checked with several onocologists and they all said that TCH is preferred over TH for most patients. They said the study above used a higher dose of "T" in the TH group and a lower dose of "T" in the TCH group and that most clinicians believe that accounts for why the TCH and TH groups did similarly. They said it's best to use the "C" and the lower dose of "T" to keep side effects at bay and still get the same effectiveness. I don't know if all of that is correct but that's what they said.

[Andrea Barnett Budin]

Thanks for that, Ben.

I do know that way back in '98-'99 -- I got more Taxotere than those taking it today. Guess they've learned a thing or two.

I took it for 9 mnths. I think 6 wks on and 2 wks off.

And once, when I wasn't looking, they gave me a 7th wk!!!!!!! "Cause you were doing so well" (shrinkage-wise).

I was ferrying between Long Island and Boca -- carrying my FLOW SHEET with me as I travelled. Once in Boca, explaining how horrid I was feeling, my onc there (now here) said, NO WONDER YOU FEEL THIS WAY! YOU GOT 7 WEEKS OF TAXOTERE! NO ONE CAN TAKE 7 WEEKS!!!

You better believe I called LI onc with lots to say. Nurse said, It was the doctor's decision. I said, Whey're talking about MY body and MY life and I should have been included in the decision-making! And I made it clear that was the way it was going to go from that moment on.

I happen to really really like that onc. That was a major step -- going off protocol as recommended!!!!!!!!

[Jackie07]

Seems to me the BCIRG 006 trial showed TCH (C = Carboplatin)has better 'Health-Related Quality of Life' than the AC -T or AC-TH (C = Cytoxan/Cyclophophamide)combinations.

Lani's post on BCIRG 007 further proved that TH and TCH are literally the same.

I believe oncologists will take into consideration our tumor features. Certain traits/parts of the tumor cells respond to anthracycline and some respond better to the Platinum-based drugs.

[BonnieR]

Ben, it's great that your doctors are on top of things and know the finer points of the study. That is reassuring I remember asking my onc about something I had read and she was able to tell me why it did not apply to my situation or was not advised
Keep the faith

[linn65]

After reading all these posts I finally understood what the first post meant. Then my next thought was I have no idea of the dosage I had of TC and the only reason I know the 400 mg of Herceptin is because I was delaying a treatment until the next week, and I asked because of this board and wondered if I was going to need a "Loading Dose".

Now, I am wondering since we know TH and TCH is kind of the same if you have more T with the TH then it equals the same as the TCH. Whew!! I have no idea what my TH dosage was and of course I am curious, so I am going to have to ask the nurse what it was on my next H...LOL.

Lani and Jackie are genious peeps, so you guys need to dummy it down for the layman person like me.

[Andrea Barnett Budin]

YES!!! I ditto what Linn just posted.

And I too -- allllll these many yrs later -- what to know details.

I DO know that I got a loading dose of H.

H was approved by the FDA, fast-tracked out of clinical trials, SEPTEMEBER 28, 1998. I was dx in Aug of '98.

I knew about HER2 -- and I asked to be tested, when "I" discovered my metastasis!!

When I would ask questions about H, doc would tell me, WE DON'T KNOW. THERE ARE NO STUDIES. "YOU" ARE IN UNCHARTERED WATERS. THEY WILL BE WRITING ABOUT YOU...

My Inner Voice told me to go w/H...

Lani, Jackie -- propeller heads that we love -- please dummy it down for us. We're just muddling through all that lingo -- skipping to CONCLUSION/RESULT... and still feel a bit lost... Thanks all!

[linn65]

Yes, Andi if I could have only hit"like". Just give us the conclusions or end results! I start talking to the doctor in all the jargon....he will say...stay off the Internet! Oops too late. Lol.

[Andrea Barnett Budin]

YES! I LOVE "like"...! Ya think we could institute a LIKE button on the HER2 site?! Wouldn't that be the coolest?!

I have brought PRINT OUTS from the Internet. My docs know not to mess with me. And Paul memorizes them! (Photographic memory...) After we all talk, Paul interprets for me. Actually my fav onc offers intelligible answers for ALL of us to comprehend.

LIKE!

ANDI