medscape article

[sarah]

Here's part of a medscape article:

Retreatment With Trastuzumab-based Therapy After Disease Progression following Lapatinib in HER2-positive Metastatic Breast Cancer

S. Gori; F. Montemurro; S. Spazzapan; G. Metro; J. Foglietta; G. Bisagni; A. Ferzi; R. R. Silva; T. Gamucci; M. Clavarezza; L. Stocchi; A. Fabi; F. Cognetti; E. Torrisi; D. Crivellari
Authors and Disclosures
Posted: 06/04/2012; Ann Oncol. 2012;23(6):1436-1441. © 2012 Oxford University Press

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• Abstract and Introduction
• Patients and Methods
• Results
• Discussion

• References

Abstract and Introduction

Abstract

Background: Preclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2)-positive breast cancer cells.
Patients and methods: Between January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression.
Results: Visceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease ≥6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5–10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2–5.6) and overall survival (OS) 19.4 months (95% CI 14.0–25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021).
Conclusion: Retreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS.
Introduction

The development of trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of human epidermal growth factor receptor 2 (HER2), has represented a major breakthrough in the treatment of HER2-positive breast cancer. Randomized trials have shown that trastuzumab-based therapies prolong survival of these patients both in the metastatic and adjuvant setting.[1–4]
In HER2-positive metastatic breast cancer, HER2 remains an effective therapeutic target even in the presence of disease progression due to trastuzumab treatment. Three phase III randomized trials have been conducted in HER2-positive metastatic breast cancer patients who have progressed after trastuzumab-based therapy. In two studies, trastuzumab beyond progression given in combination with capecitabine or with lapatinib (the dual HER1/HER2 tyrosine kinase) resulted more effective than capecitabine alone or single-agent lapatinib, respectively.[5, 6] The third study has shown that lapatinib plus capecitabine significantly improves the time to progression compared with capecitabine monotherapy,[7] and in 2007, this combination was approved for the treatment of HER2-positive metastatic breast cancer pretreated with an anthracycline, a taxane and trastuzumab.[8] Nonetheless, it is necessary to know how to treat patients after disease progression on lapatinib and capecitabine.
Preclinical evidence could support the reuse of trastuzumab after treatment with lapatinib. The development of acquired resistance to trastuzumab might also be due to receptor degradation and down-regulation.[9, 10] Lapatinib, inducing stabilization and accumulation of inactive HER2 receptor at the cytoplasmic membrane, could potentially resensitize HER2-positive tumor cells to the action of trastuzumab.[11]
This study reports on the clinical outcome of HER2-positive metastatic breast cancer patients who were rechallenged with trastuzumab following disease progression on lapatinib.


article is: Retreatment With Trastuzumab-based Therapy After Disease Progression Following Lapatinib in HER2-positive Metastatic Breast Cancer

[LuckyLinda]

I spoke to my oncologist about possibly participating in a vaccine trial at Johns Hopkins (Trastuzumab, Cyclophosphamide, and Vaccine Therapy in Treating Patient With High-Risk or Metastatic Breast Cancer NCT00847171), but he seems to think I am not a candidate because I do not have metastasis-----yet. Since I am HER2+ and I had micrometastasis in 2/10 nodes (one of which escaped the membrane), I know that I am at high risk for mets. I would like to do all I can to avoid going from stage IIB to stage IV. I finished 6 ycles of TCH, and I am on Herceptin for a full year (last treatment 12/28/12) and will be starting radiation soon. Does anyone know of any studies for those of us who don't yet have "advanced" cancer. I live in Virginia Beach, so Johns Hopkins would not be out of the question, nor would Washington, D.C. I feel like I am just sitting around waiting for the cells to metastasize to my brain or spine! Thanks.

[Vicki revised]

Linda:
Your post concerns me. It sounds like you feel no control over your disease. There are hundreds of trials being conducted for different stages. I encourage you to check out links on this board as well as other reputable websites such as Komen, ACS, NIH, Mayo, etc.

[LuckyLinda]

I absolutely feel that way. Ultimately, I am relying on the expertise of my doctors and on their guidance in how best to treat my disease. I have no medical background, so I don't feel equipped to take charge of my own treatment. I can't order my own tests, I can't force the radiology department to get me in sooner, and I don't get to dictate which drugs would be most effective to treat my cancer. I couldn't even persuade my gynecologist's office to see me when I found a lump in my breast. It took a week and a complaint to the office manager, to get in. And it was October--National Breast Cancer Awareness month. I'm just trying to go with the flow, stay as positive as possible, and discuss my treatment options with my doctor in as intelligent a manner as I can. And I really like my oncologist and trust that he is doing what is best for me. But I do get frustrated when I read these signatures and realize that so many of the subscribers have been through the very same treatments only to find a year (or five years) down the road that their cancer has metastasized. There are days (like today when I am waiting for my oncologist's secretary to schedule my radiology consult and she leaves a message telling me that they are really busy but will try to "squeeze" me in sometime in the next week) when I get really scared that these "aggressive" cells are going to get away from me before the targetted treatment can stop them. The wheels move so slowly. I hope I am not the only person who gets frustrated and feels like things should move faster.

[Vicki revised]

I would be livid if I got such a message from any of my medical team! I chose not to use the large hospital based multi-physician group in our town (there are only 2), instead opting for a small clinic because of that very kind of response. For my 2nd opinion I went to UA Birmingham, one of the top bc centers in the US where my original dx was affirmed and learned how highly thought of and respected my small practice oncologist is. That's a story better suited for another thread, but I feel empowered by the team at the clinic, they are fighting this battle WITH me.

Voice your concerns and irritations to your doctor about not feeling empowered and also stay in touch with this group. You will learn SO much on these boards.

God Bless

[LuckyLinda]

Thank you, Vicki. I'm still waiting for the phone to ring and trying not to spend all of my time fixating on cancer. I do get a lot of inspiration from the wonderful, strong, ladies who post here. The "relationship" thing between the doctor's staff and the patient (there's a reason why the term "patient" is assigned) is a tricky one. I don't want to be identified as a pain in the ass. On the other hand, this is my life, my disease, and no one else is as affected by this as I am. It has now been 4 weeks since I finished TCH. I asked about a referral to radiology 4 weeks ago at my last TCH infusion and was told by the nurse practitioner that the oncologist would take care of that at my next appointment. I asked again last Wednesday and he told me that his secretary would schedule that appointment. I'm still waiting. It seems to me that if radiology had been contacted 4 weeks ago, they would not now be trying to "squeeze" me in. I knew I would require radiation. I had already met with the radiation oncologist back in February. My oncologist knew that I would require radiation. I know they deal with desperate patients on a daily basis, many in more critical situations than mine, but, again, I can only worry about my cancer. I apologize for whining. I will keep you informed when I finally have an appointment scheduled. Thank you for listening. ♥

[Becky]

Call back everyday - twice a day. In the morning and again in the afternoon. The greasy wheel does get oiled. Then also look into a consult elsewhere. Ask your current onc office for a copy of your chart - your full chart - now - today. A consult somewhere else will want that.

Usually radiation starts 4-8 weeks after chemo ends so you are still in a good window but they do have to "chart" your chest for radiation and that takes a week or so.

You can do this as you have already admitted that this does not affect anyone like it affects you and that is so true. Your feathers are a bit ruffled now so really ruffle them up now and call now for an appointment where you are at now. If you get no results, call in the afternoon and if no results, demand a copy of your chart to be picked up tomorrow morning. Look for another consult to make an appointment with now and make an appointment.

I was never a rock the boat person either until my onc (at the time) wouldn't give me Herceptin. I did the above and got another onc and got Herceptin. (Then my current onc called and said, "Becky, all you had to do was ask and I would have given you Herceptin". I told him I did a dozen times).

Go for it. We are here for you and cheering you on. This will be on your mind until you have an appointment.

[LuckyLinda]

Thank you for being a cheering squad, Becky. I called the radiologist's office directly this morning to see if the appointment had been scheduled. He did not see an appointment for me, but he promised to contact my oncologist's secretary and call me back today whether an appointment is scheduled or not. I have already had a consult with the radiation oncologist, so I'm not even a new patient. The sooner I start, the sooner I will be able to travel again and leave town for more than a quick overnight getaway. So, I'm keeping my fingers crossed, and I will continue to be a squeaky wheel. I do really like my oncologist. I feel like it is the staff that is letting me down, not him. He did tell me that he would call his contacts at Johns Hopkins to see if there are any studies for which I would qualify. Thanks again for the push.

[Vicki revised]

Any word from the radiologist today? You are fighting for your life and you are NOT being unreasonable in expecting professional conduct by a doctor's staff. This isn't the same thing as calling to get an appt for a sinus infection but the runaround you are getting sounds like it!

[LuckyLinda]

Hi Vicki revised,

I got a call back yesterday from a very nice young lady in the radiologist's office. She explained that they are undergoing an "equipment update" and going back and forth between two offices, so things are a bit busier than usual. But.........she agreed that I needed to be seen soon, and she worked me into the schedule for both a short consult with my doctor (with whom I already had a [I]lengthy[I] consult back in February) and for the CT scan required for the marking. I may have a bit of a wait, but I'm okay with that. I also have an appointment next week with my breast surgeon, who I haven't seen since January, so I'm very relieved. Thank you again for your advice and encouragement. I've never had an aggressive bone in my body, but I think it's time that I grow one.

[sarah]

linda, seek 2nd, 3rd opinions, you must be aggressive with this disease. i had dcis no nodes, etc and asked about herceptin but at that time I was refused and now my disease had progressed and I have invasive cancer. it's in NED (they say) but honestly my cancer has NEVER been seen in tests, only biopsies. so i urge you to find other doctors and to treat this disease aggressively. I do not mean to scare you but only to make you become pro-active but this is a very aggressive and cunning disease. fight it. demand attention and treatment.
love sarah