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Old 11-01-2011, 09:35 AM   #1
Lani
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Thumbs up for Stage IVs-- proof herceptin still beneficial even after resistance 2 lapatinib

develops"

Ann Oncol. 2011 Oct 29. [Epub ahead of print]
Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer.
Gori S, Montemurro F, Spazzapan S, Metro G, Foglietta J, Bisagni G, Ferzi A, Silva RR, Gamucci T, Clavarezza M, Stocchi L, Fabi A, Cognetti F, Torrisi E, Crivellari D.
Source
Department of Medical Oncology, S. Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia.
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.

PMID: 22039084
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Old 11-01-2011, 07:19 PM   #2
Rich66
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Re: for Stage IVs-- proof herceptin still beneficial even after resistance 2 lapatini

I wonder if there is a crosstalk mechanism involved that could be exploited..i.e. bounce between Herceptin and Tykerb. Thoughts?
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Old 11-02-2011, 05:09 AM   #3
kykeon22
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Re: for Stage IVs-- proof herceptin still beneficial even after resistance 2 lapatini

Unfortunately I have no thoughts, but the news is amazingly stunning. Great thing. XD
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She has been dignosed in February 2008 BC state IV, left breast multiple nodes size 5 cm, mets lungs and liver. Er+ Pr+ Her neu +++.
3/2008 - 10/2010 Herceptin + Aramidex NED
10/2010 recurrence lung met, pleural effusion, toracentesis
11/2010- Tyverb + Navalbine NED
08/2011 CA-15-3 = 90 scan
08/2011 Scan revealed reccurrence lung met, tiny metastasis on the pleura and pleural effusion.
4 pills tyverb, mytoxantrone once ever three weeks, and Aromasin.
Tykerb and taxol, sever allergic reaction
Tykerb taxotere
Herceptin, perjeta, gemcitabina
C- diff, bad diarrea
Halevan and tamoxifen, tm down from 1200 to 130

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Old 11-02-2011, 05:27 PM   #4
CoolBreeze
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Re: for Stage IVs-- proof herceptin still beneficial even after resistance 2 lapatini

I will start herceptin again next week. I wonder if I should ask for Tykerb to be added to the regimen? I dread the SEs, considering I have to work far from a bathroom.
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08/17/09 Dx'd.
Multifocal/multicentric IDC, largest 3.4 cm, associated ADH, LCIS, DCIS
HER2+ ER+/PR- Grade 3, Node Negative

10/20/2009: Right mastectomy, reconstruction with TE
12/02/2009: Six rounds TCH, switched to Taxol halfway through due to neuropathy
03/31/2010: Finished chemo
05/01/2010: Began tamoxifen, the worst drug ever
11/18/2010: Reconstruction completed
12/02/2010: Finished herceptin
05/21/2011: Liver Mets. Quit Tamoxifen
06/22/2011: Navelbine/Zometa/Herceptin
10/03/2011: Liver Resection, left lobe. Microwave ablation, right lobe - going for cure!
11/26/2011: C-Diff Superbug Infection, "worst case doctor had seen in 20 years"
03/28/2012: Progression in ablated section of the liver - no more cure. Started Abraxane, continue herceptin/zometa
10/10/2012: Progression continues, started Halaven, along with herceptin and zometa.
01/15/2013: Progression continues, started Gemzar and Perjeta, an unusual combo, continuing with herceptin and zometa
03/13/2013: Quit Gemzar, body just won't handle it. Staying on herceptin, zometa and perjeta.
04/03/2013: CT shows 50% regression in tumor, so am starting back on Gemzar with dose reduction, staying with perjeta/herceptin/zometa. Can't argue with success!
05/09/2013: Discussing SBRT with Radiology due to inability of bone marrow to recover from chemo.
06/07/2013: Fiducial placement for SBRT
07/03/2013: Chemo discontinued, on Perjeta, Herceptin and Zometa alone
07/25/2013: SBRT (gamma knife) begins
08/01/2013: SBRT completed
08/15/2013: STABLE! continuing with Perjeta, Herceptin, Zometa
06/18/2014: ***** NED!!!!***** continuing with Perjeta, Herceptin, Zometa
01/29/2014: Still NED. continuing with Perjeta, Herceptin. Zometa lowered to every 3 months instead of monthly.
11/08/2015: Progression throughout abdomen and lungs. Started TDM-1, aka Kadcyla. Other meds discontinued. Remission was nice while it lasted.

5/27/18: Stable. Kadcyla put me right back in the barn. I have two teeny spots on my lungs that are metabolically inactive, and liver is clean.

I’m beating this MFer. I was 51 when this started and had two kids, 22 and 12. Now I’m 60. My oldest got married and trying to start s family. My youngesg graduates from Caltech this June. My stepdaughter gave me grandkids. Life is fantastic.
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