New Phase II Trial of Combined Monoclonal Antibodies
 

I'm not surprised as pertuzumab is a HER1,2 & 3 receptor inhibitor. There is a high correlation with HER2 and the others. I think the next step will be to combine that combination with Avastin but I guess time will tell.

Good luck,
Al

Lori,
Had you received any treatments prior to going into this study?
Kim from CT

Exciting stuff
 

Dear Lori,
Thanks for posting this - you may want to also post this under the Clinical Trials area (OOPS, NEVER MIND! I JUST SAW IT THERE, TOO!:). It's exciting to see they are seriously studying these combinations that target more pathways - aiming to shut down all the sneaky avenues. I keep the following article - a poster from the 2004 SABCS as a reminder that there may just be the "miracle" combination out there. I hope this trial will be super successful for you. Thanks for posting, and do keep us updated if you can!

Regards
Chris
[23] Complete disappearance of ER+/HER2+ breast cancer xenografts with the combination of gefitinib, trastuzumab, and pertuzumab to block HER2 cross-talk with ER and restore tamoxifen inhibition.

Arpino G, Weiss H, Wakeling AE, Osborne K, Schiff R.. Baylor College of Medicine, Houston, TX; AstraZeneca, Macclesfield, United Kingdom

Background. Tamoxifen (Tam) stimulates growth of ER+, HER2-overexpressing MCF7/HER2-18 breast tumor xenografts as a mechanism of Tam resistance. Anti-EGFR/HER2 treatment with either the tyrosine kinase inhibitor gefitinib ( Iressa , Gef) or the monoclonal antibody trastuzumab ( Herceptin , H) eliminates the ER-EGFR/HER2 cross-talk and temporarily restores Tam growth inhibition. Although the combination of Gef plus H is better than either agent alone, resistance still develops in 2-3 months and tumor growth resumes. Pertuzumab (P) is a new antibody targeting HER2 that inhibits heterodimerization of HER2 with all other HER family members and reduces HER2 signaling. We evaluated P as a single agent and in various combinations with Tam, Gef, and H in this model of in vivo Tam resistance.
Methods. Mice bearing MCF-7/HER2-18 cell xenografts established in the presence of estrogen (E2) were randomized (n 16) to continued E2 (+E2), E2 withdrawal ( E2), or E2 plus Tam alone or with various combinations of Gef, H, and P. Rates of complete disappearance of palpable tumor (CR), and median time to tumor progression (TTP) were determined and compared in the various treatment groups.
Results. In the +E2 group, P, like Gef and H, only minimally inhibited E2-stimulated tumor growth. In the -E2 group, however, the addition of P increased CRs from 0% ( E2 alone) to 56% ( E2+P) and TTP from 74 days to more than 140 days. In the Tam group, the addition of Gef, H, or P alone temporarily blocked Tam-stimulated growth and stabilized tumor volume (TTP=98 days p<0.001; 105 days, p<0.0001; and 84 days, p<0.0001, respectively). CRs were observed with the combination of Tam plus H (33%) or plus P (28%), but not plus Gef (0%). Since P, H, and Gef inhibit HER2 signaling in slightly different ways, combination therapy was investigated. In mice given Tam, the addition of P with H had a more dramatic effect, with 71% (12/17) of mice achieving a CR. The TTP has not yet been reached although 4 tumors are now progressing at 133 days of treatment. Even more remarkable effects were observed when all 3 growth factor inhibitors were combined with Tam: CR was observed in 90% (18/20) of mice and no tumors have progressed at a median follow up 129 days. Drug toxicity was not evident even with the combination regimens.
Conclusion. Growth factor receptor inhibitors cooperate through distinct, yet complementary, mechanisms to convey a potent HER2 signaling blockade. Combination treatment blocks crosstalk with ER to restore Tam antagonist effect on ER, and together with Tam eradicate MCF7/HER218 tumors. Because growth of these tumors seems to depend mainly on ER and EGFR/HER2 pathways, complete targeted disruption of these pathways can achieve remarkable antitumor activity deserving a clinical trial.


Friday, December 10, 2004 10:00 AM

General Session 4 (9:30 AM-12:00 PM)

Kim,
I was originally diagnosed 8/03 grade 3 DCIS, stage III, and 8/15 lymph nodes with cancer. I had neo-adjuvant treatment consisting of 3 Taxotere and 5 A/C dose dense, followed by left mastecomy & level 1 axillary node dissection, then 4 1/2 weeks of radiation, then 52 weeks of Herceptin which I completed in 5/05. Mets to lungs were diagnosed 12/05 and I received 6 cycles of Xeloda (3,000mg) before starting this trial. For most part my disease was stable on Xeloda but last scans revealed slight progression so my oncologist thought that it was best to move onto something new.

Lori

Dear Lori,
It is interesting to see that you were accepted even with prior treatment and some progression. You must have a great oncologist who encouraged you to try a trial ... it is a very interesting trial and seems so promising; will you please keep us posted on your progress and any paper that your researchers publish or present? I was in the Seattle tumor vaccine group trial; I am wondering if that would preclude my participation in other trials. Well for now, I will sit tight and watch your progress with interest; and if i my mets progress, i can always call the number you posted. Thank you for sharing, I look forward to your future posts!
Love Kim from CT

Just wanted to update you all on my latest ct scans after completing 4 cycles of herceptin & pertuzumab. My tumors in my lungs have reduced between 8% & 9% since my start in the trial on 5/31. There is one patient who has achieved a 27% reduction after 4 cycles. Our sample in this trial is small - 9 total enrolled; 4 have dropped out as their disease has progressed.

My next scans will be at the end of September when I hope to also achieve that 27% reduction as well! To date, I feel great with minimal side effects. Thank God!

Lori AWESOME NEWS!!!
 

I TOO hope you get the 27% (AND MORE). Take care and God bless.

Rhonda

Dear Lori,

Keep up the good work! I hope every ct scan is an improvement. Best of luck to you!

I am hoping and praying for your continued success. Keep up the good work!

Lori-


Thanks for keeping us posted - I am currenly on xeloda/tykerb, but am always looking ahead if I need something else. I wish you continued success with it...

Regards,
Shell

I received the results from my CT scan this past Tuesday 10/3. The scan is after completing 6 cycles of herceptin and pertuzumab given every three weeks. This scan was very disappointing as no further reduction was noted. There was very slight progression (3mm) in one of the larger masses measuring about 4.6 cm.

I will continue on this treatment and we will review again in 6 weeks after my next scan.

I am very discouraged and am starting to lose hope in this battle.

Lori,

I know it's easier said than done but don't ever loose hope in this battle. The results are not what you had hoped but there was only a very slight progression. And, remember you had a significant reduction last time. Perhaps, you have reached a plateau. Hpefully, in six weeks when your CT is repeated the results will show some additional reduction. Keep us posted!

Lori,

Please don't give up hope I am in a simular position as you are.I just had my catscan and it showed 25% increase in my liver mets. So I had to stop the Tykerb clinical trial. So we can't give in to this horrible beast I will go to my doctor on tuesday and see what I have left for treatment options. Please know you have all my prayers to help you through this. Please keep us posted on how you are doing.

Hi Lori, Haven't been there yet, but .3mm is small. My MRI was off by 1.5 cm so this may not mean lot. If the next scan shows things bigger then I'd be thinking about plan B. Hoping all improves. Keep us posted as it is so helpful to know what works. BB

Thank you for your encouragement and support. It is hard to be positive when 7 out of 10 patients enrolled to date have been dropped from the trial due to either disease progression or cardiac toxicity.
I am hoping that the CT scan was off and that I will have better results next time around.

Lori