Abstract 3426
Background
Subgroup analyses of randomized, controlled trials (RCTs) using high dose chemotherapy (HD) with autologous stem cell support (autoSCT) reveal a potential benefit of HD in patients with triple negative breast cancer (TNBC) and in tumors harboring features of HRD (Vollebergh et al, 2011). The phase III part of the neo-TN RCT, compared neo-adjuvant HD with conventional treatment (CONV) in BRCA1-like TNBC.
Methods
Patients with cT2-3N0-3M0 TNBC with HRD were randomized between HD or CONV after 3 courses of 2-weekly doxorubicin/cyclophosphamide (ddA60C600). CONV treatment consisted of another 3xddAC, or in case of an unfavorable response on MRI a switch to 3 cycles capecitabine800BID14-7/docetaxel75; after an amendment all patients switched to 3xcarboplatinAUC6/paclitaxel80weekly. The HD regimen consisted of a 4th course ddAC and 2 courses of cyclophosphamide3000d1/carboplatin400d1,2/ thiotepa250d2 both followed by autoSCT. Primary outcome was the Neo-adjuvant Response Index (NRI), secondary outcomes included overall (OS) and recurrence free survival (RFS).
Results
From 2010 to 2016, 122 patients were randomized (intention-to-treat). Median follow-up is 45 months. There was no significant difference in NRI between HD and CONV (mean NRI 0.78 versus 0.72, range 0-1, p = 0.41 Wilcoxon test). An NRI of > 0.7 was strongly associated with good prognosis (RFS of 97% [95%CI 93%-100%] versus 67% [95%CI 55%-82%] at 4 years). See Table for 4-years OS and RFS comparing HD with CONV. There were no treatment related deaths. However, 7 out of 55 patients who actually received HD did not complete HD mainly because of infections or allergic reactions.Table:
187P
HD % (95%CI) | CONV % (95%CI) | HR (95%CI) | p-value | |
---|---|---|---|---|
All (n = 122) | ||||
4-yrs OS 4-yrs RFS | 92 (85-99) 92 (85-99) | 79 (69-91) 78 (68-89) | 0.43 (0.15-1.23) 0.41 (0.15-1.07) | 0.12 0.07 |
Stage III only (n = 35) | ||||
4-yrs OS | 93 (81-100) | 60 (39-93) | 0.14 (0.02-1.14) | 0.07 |
Conclusions
No significant efficacy differences were found between HD and CONV. The NRI is of prognostic value. Whether the HD regimen is promising, especially in very high risk BRCA1-like TNBC [HR = 0.14], requires additional data including a comparison with platinum treatment in all control arm patients.
Clinical trial identification
NCT01057069.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The Dutch Cancer Foundation (KWF) and by the Schumacher Kramer Foundation.
Disclosure
S.C. Linn: Research grant / Funding (self), research support for patients fees in D-Care study: Amgen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Research grant / Funding (self): Genentech; Advisory / Consultancy: IBM; Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (institution), patients fees in TEAM 2b study: Pfizer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Speaker Bureau / Expert testimony, Fee for teaching, paid to institution: Bayer. All other authors have declared no conflicts of interest.
Resources from the same session
5489 - Local immune status in cancer cell nests can be a predictor of survival for rectal cancer with neoadjuvant radiotherapy
Presenter: xijin lin
Session: Poster Display session 2
Resources:
Abstract
1653 - Impact of concomitant medications on disease free survival (DFS) and overall survival (OS) in patients from the PETACC8 study.
Presenter: Clémence Brun
Session: Poster Display session 2
Resources:
Abstract
5206 - Updated results of NORDIC 8, a randomised trial of cetuximab every 2 weeks with FOLFIRI or cetuximab with alternating FOLFIRI/FOLFOX in patients with RAS and BRAF wild type metastatic colorectal cancer.
Presenter: Per Pfeiffer
Session: Poster Display session 2
Resources:
Abstract
2992 - Clinical impact of mucinous and poorly differentiated tumors on the outcome of patients with stage II colon cancer: a TOSCA subgroup analysis
Presenter: Gerardo Rosati
Session: Poster Display session 2
Resources:
Abstract
4753 - Exercise improved adjuvant treatment completion rates and treatment-related toxicities in colorectal cancer: A prospective pilot study
Presenter: Hong Jun Kim
Session: Poster Display session 2
Resources:
Abstract
2735 - Bevacizumab plus Oxaliplatin-Based Chemotherapy as Adjuvant Treatment for Colon Cancer (CC): Updated analysis of stage II disease from the AVANT Phase III Randomized trial by the GERCOR Group
Presenter: Aimery De Gramont
Session: Poster Display session 2
Resources:
Abstract
1843 - Multicenter Validation of the Postoperative Carcinoembryonic Antigen Combined Prognostic Model for Stage Ⅲ Colon Cancer
Presenter: Ji Zhu
Session: Poster Display session 2
Resources:
Abstract
2554 - Impact of the IDEA study on clinical practice for stage III colon cancer patients: a French GERCOR - FFCD - GI UNICANCER national survey.
Presenter: Kaissa Ouali
Session: Poster Display session 2
Resources:
Abstract
3285 - Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer
Presenter: Philip Falk
Session: Poster Display session 2
Resources:
Abstract
3905 - Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer
Presenter: Krittiya Korphaisarn
Session: Poster Display session 2
Resources:
Abstract