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06-07-2015, 07:54 PM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Nadia Harbeck-- ADAPT trial using 12 wks of TDM1 NEOADJUVANT+/- antiestrogen followed
by usual chemo+ 1 yr herceptin markedly increases pCR rate in her2+ er+s, a group usually with many fewer pCRs thab her2+er-s.
http://meetinglibrary.asco.org/content/111835?media=vm
Efficacy of 12-weeks of neoadjuvant TDM1 with or without endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer: WSG-ADAPT HER2+/HR+ phase II trial.
Subcategory:
HER2+
Category:
Breast Cancer—HER2/ER
Meeting:
2015 ASCO Annual Meeting
Session Type and Session Title:
Oral Abstract Session, Breast Cancer—HER2/ER
Abstract Number:
506
Citation:
J Clin Oncol 33, 2015 (suppl; abstr 506)
Author(s):
Nadia Harbeck, ...
Abstract:
Background: Evidence suggests differential efficacy of standard neoadjuvant chemo- + targeted therapy in HER2+ early breast cancer (eBC) according to hormone-receptor (HR) status. ADAPT HER2+/HR+ aims to identify responders to dual targeted therapy, which has not been widely explored. Methods: 380 patients (pts) receive 12 weeks of neoadjuvant therapy. Arms A/B: T-DM1 (3.6 mg/kg q3w) ± endocrine therapy (ET) (pre-: tamoxifen; postmenopausal: aromatase inhibitor); Arm C (control): q3w trastuzumab + ET. After surgery, pts are to receive 4xEC – 12xpaclitaxel weekly (investigators’ discretion) and complete 1y trastuzumab. Trial tests pCR (yPN0 and ypT0/is) in Arms A and B compared to control (C). Biomarkers are measured at baseline and after 3 weeks. Results: Pre-planned interim analysis (n = 130) aimed to identify an early-response biomarker (e.g. Ki-67 drop) and to validate trial assumptions. Median age was 49 years; 55% were pre-menopausal; 40% had cT1 tumors, 51% cT2; 68% had cN0, 27% cN1; 75% had G3. Median baseline Ki67 was 30%. In all arms, 95-100% received all 4 therapy cycles. 15 SAEs occurred in 12 pts (A:4; B:6; C:2), majority are CTC grades 2 (9) or 3 (4); all pts completely recovered without sequelae. Overall pCR rate was 30.8%: A: 40.5%, B: 45.8%, C: 6.7%. The difference between either arm A or B vs. C was significant (p < 0.001), but not A vs. B. Exploratory analysis suggests benefit of adding ET to T-DM1 in pre- (pCR: 28.6% for T-DM1 single agent vs. 47.6% with ET) but not in postmenopausal pts (pCR: 64.3% vs. 50%). Ki-67 quantification in the 3-week biopsy was not possible in 43.1%, mostly due to low tumor cell counts ( < 500); of the remaining tumors, 21.6% (16/74) had Ki-67 ≤ 10% after first cycle. Final data set is required to substantiate these findings which may also be impacted by the different ET options (Tam vs. AI). Conclusions: The interim analysis demonstrates for the first time clinically meaningful pCR rates ( > 40%) after only 12 weeks of T-DM1 ± ET without systemic chemotherapy in HER2+/HR+ eBC. Ongoing biomarker analyses include PI3K mutations and intrinsic subtypes. In 1/2015, registration phase was completed at 449 pts. Clinical trial information: NCT01745965 |
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06-09-2015, 12:42 PM
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#2
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Senior Member
Join Date: May 2011
Location: Denver, CO
Posts: 1,427
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Re: Nadia Harbeck-- ADAPT trial using 12 wks of TDM1 NEOADJUVANT+/- antiestrogen foll
Well, I'd love to see the video but the one-day guest pass was not enough to allow me to view it. The cost to get it is $495--a bit rich for my blood. I'll go back and study the abstract.
__________________
Amy
_____________________________
4/19/11 Diagnosed invasive ductal carcinoma in left breast; 2.3 cm tumor, 1 axillary lymph node, weakly ER+, HER2+++
4/29/11 CT scan shows suspicious lesions on liver and lungs
5/17/11 liver biopsy
5/24/11 liver met confirmed--Stage IV at diagnosis
5/27/11 Begin weekly Taxol & Herceptin for 3 months (standard of care at the time of my DX)
7/18/11 Switch to weekly Abraxane & Herceptin due to Taxol allergy
8/29/11 CT scan shows no new lesions & old lesions shrinking
9/27/11 Finish Abraxane. Start Herceptin every 3 weeks. Begin taking Arimidex
10/17/11--Brain MRI--No Brain mets
12/5/11 PET scan--Almost NED
5/15/12 PET scan shows progression-breast/chest/spine (one vertebra)
5/22/12 Stop taking Arimidex; stay on Herceptin
6/11/12 Started Tykerb and Herceptin on clinical trial (w/no chemo)
9/24/12 CT scan--No new mets. Everything stable.
3/11/13 CT Scan--two small new possible mets and odd looking area in left lung getting larger.
4/2/13--Biopsy of suspicious area in lower left lung. Mets to lung confirmed.
4/30/13 Begin Kadcyla/TDM-1
8/16/13 PET scan "mixed," with some areas of increased uptake, but also some definite improvement, so I'll stay on TDM-1/Kadcyla.
11/11/13 Finally get hormone receptor results from lung biopsy of 4/2/13. My cancer is no longer ER positive.
11/13/13 PET scan mixed results again. We're calling it "stable." Problems breathing on exertion.
2/18/14 PET scan shows a new lesion and newly active lymph node in chest, other progression. Bye bye TDM-1.
2/28/14 Begin Herceptin/Perjeta every 3 weeks.
6/8/14 PET "mixed," with no new lesions, and everything but lower lungs improving. My breathing is better.
8/18/14 PET "mixed" again. Upper lungs & one spine met stable, lower lungs less FDG avid, original tumor more avid, one lymph node in mediastinum more avid.
9/1/14 Begin taking Xeloda one week on, one week off. Will also stay on Herceptin and Perjeta every three weeks.
12/11/14 PET Scan--no new lesions, and everything looks better than it did.
3/20/15 PET Scan--no new lesions, but lower lung lesions larger and a bit more avid.
4/13/15 Increasing Xeloda dose to 10 days on, one week off.
7/1/15 Scan "mixed" again, but suggests continuing progression. Stop Xeloda. Substitute Abraxane every 3 weeks starting 7/13.
10/28/15 PET scan shows dramatic improvement everywhere. All lesions except lower lungs have resolved; lower lungs noticeably improved.
12/18/15 Last Abraxane. Continue on Herceptin and Perjeta alone beginning 1/8/16.
1/27/16 PET scan shows cancer is stable.
5/11/16 PET scan shows uptake in some areas that were resolved on the last two scans.
6/3/16 Begin Kadcyla and Tykerb combination
6/5 - 6/23 Horrible diarrhea from K&T together. Got pneumonia.
7/15/16 Begin Kadcyla only every 3 weeks.
9/6/16 Begin radiation therapy on right lung lesion that caused the pneumonia.
10/3/16 Last of 12 radiation treatments to right lung.
11/4/16 Huffing and puffing, low O2, high heart rate, on tiniest bit of exertion. Diagnosed as radiation pneumonitis. Treated with Prednisone.
11/11/16 PET scan shows significant improvement to radiated part of right lung BUT a bunch of new lung lesions, and the bone met is getting worse.
11/22/16 Begin Eribulin and Herceptin. H every 3 weeks. E two weeks on, one week off.
3/6/17 Scan shows progression in lungs. Bone met a little better.
3/23/17 Lung biopsy. Tumor sampled is ER-, PR+ (5%), HER2+++. Getting Herceptin and Perjeta as a maintenance treatment.
5/31/17 Port placement
6/1/17 Start Navelbine & Tykerb
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06-10-2015, 07:20 AM
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#3
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Member
Join Date: Feb 2014
Posts: 11
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Re: Nadia Harbeck-- ADAPT trial using 12 wks of TDM1 NEOADJUVANT+/- antiestrogen foll
Great to see how effective tamoxifen was in premenopausal. For someone who was worried about its effectiveness in her2+, it is relieving. Thanks for sharing.
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06-10-2015, 02:32 PM
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#4
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Senior Member
Join Date: May 2011
Location: Denver, CO
Posts: 1,427
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Re: Nadia Harbeck-- ADAPT trial using 12 wks of TDM1 NEOADJUVANT+/- antiestrogen foll
Dear ConcernedStu:
The difference in this trial was the TDM-1. Arm A had TDM-1 plus the appropriate endocrine therapy for their menopause status. Arm B just had TDM-1. The control group had Herceptin plus endocrine therapy (and not TDM-1). It did much less well in terms of pathological complete response than both arms of the experimental group.
Although there was not a significant difference between Arm A and Arm B, within Arm B there was a difference between the pre-menopausal (Tamoxifen) and post-menopausal (AI) subgroups.
__________________
Amy
_____________________________
4/19/11 Diagnosed invasive ductal carcinoma in left breast; 2.3 cm tumor, 1 axillary lymph node, weakly ER+, HER2+++
4/29/11 CT scan shows suspicious lesions on liver and lungs
5/17/11 liver biopsy
5/24/11 liver met confirmed--Stage IV at diagnosis
5/27/11 Begin weekly Taxol & Herceptin for 3 months (standard of care at the time of my DX)
7/18/11 Switch to weekly Abraxane & Herceptin due to Taxol allergy
8/29/11 CT scan shows no new lesions & old lesions shrinking
9/27/11 Finish Abraxane. Start Herceptin every 3 weeks. Begin taking Arimidex
10/17/11--Brain MRI--No Brain mets
12/5/11 PET scan--Almost NED
5/15/12 PET scan shows progression-breast/chest/spine (one vertebra)
5/22/12 Stop taking Arimidex; stay on Herceptin
6/11/12 Started Tykerb and Herceptin on clinical trial (w/no chemo)
9/24/12 CT scan--No new mets. Everything stable.
3/11/13 CT Scan--two small new possible mets and odd looking area in left lung getting larger.
4/2/13--Biopsy of suspicious area in lower left lung. Mets to lung confirmed.
4/30/13 Begin Kadcyla/TDM-1
8/16/13 PET scan "mixed," with some areas of increased uptake, but also some definite improvement, so I'll stay on TDM-1/Kadcyla.
11/11/13 Finally get hormone receptor results from lung biopsy of 4/2/13. My cancer is no longer ER positive.
11/13/13 PET scan mixed results again. We're calling it "stable." Problems breathing on exertion.
2/18/14 PET scan shows a new lesion and newly active lymph node in chest, other progression. Bye bye TDM-1.
2/28/14 Begin Herceptin/Perjeta every 3 weeks.
6/8/14 PET "mixed," with no new lesions, and everything but lower lungs improving. My breathing is better.
8/18/14 PET "mixed" again. Upper lungs & one spine met stable, lower lungs less FDG avid, original tumor more avid, one lymph node in mediastinum more avid.
9/1/14 Begin taking Xeloda one week on, one week off. Will also stay on Herceptin and Perjeta every three weeks.
12/11/14 PET Scan--no new lesions, and everything looks better than it did.
3/20/15 PET Scan--no new lesions, but lower lung lesions larger and a bit more avid.
4/13/15 Increasing Xeloda dose to 10 days on, one week off.
7/1/15 Scan "mixed" again, but suggests continuing progression. Stop Xeloda. Substitute Abraxane every 3 weeks starting 7/13.
10/28/15 PET scan shows dramatic improvement everywhere. All lesions except lower lungs have resolved; lower lungs noticeably improved.
12/18/15 Last Abraxane. Continue on Herceptin and Perjeta alone beginning 1/8/16.
1/27/16 PET scan shows cancer is stable.
5/11/16 PET scan shows uptake in some areas that were resolved on the last two scans.
6/3/16 Begin Kadcyla and Tykerb combination
6/5 - 6/23 Horrible diarrhea from K&T together. Got pneumonia.
7/15/16 Begin Kadcyla only every 3 weeks.
9/6/16 Begin radiation therapy on right lung lesion that caused the pneumonia.
10/3/16 Last of 12 radiation treatments to right lung.
11/4/16 Huffing and puffing, low O2, high heart rate, on tiniest bit of exertion. Diagnosed as radiation pneumonitis. Treated with Prednisone.
11/11/16 PET scan shows significant improvement to radiated part of right lung BUT a bunch of new lung lesions, and the bone met is getting worse.
11/22/16 Begin Eribulin and Herceptin. H every 3 weeks. E two weeks on, one week off.
3/6/17 Scan shows progression in lungs. Bone met a little better.
3/23/17 Lung biopsy. Tumor sampled is ER-, PR+ (5%), HER2+++. Getting Herceptin and Perjeta as a maintenance treatment.
5/31/17 Port placement
6/1/17 Start Navelbine & Tykerb
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06-11-2015, 12:59 PM
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#5
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: Nadia Harbeck-- ADAPT trial using 12 wks of TDM1 NEOADJUVANT+/- antiestrogen foll
I had NO idea of the cost to view (it was included free in my meeting registration fee)
they usually become free to view 3-6 months after the meeting, so hang in there...
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