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
3139 - Efficacy and safety of FOLFIRI/Aflibercept (FA) in elderly population with mCRC after failure of oxaliplatin-based chemotherapy.
Presenter: Nieves Martinez Lago
Session: Poster Display session 2
Resources:
Abstract
3446 - Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)
Presenter: Pasquale Lombardi
Session: Poster Display session 2
Resources:
Abstract
3969 - Comparable survival outcome between Thai patients with sporadic young adult and adult onset colorectal cancer
Presenter: Kanjana Sukhokanjanachusak
Session: Poster Display session 2
Resources:
Abstract
4455 - Impact of primary tumor side on 3-year survival outcomes of first-line (1L) FOLFOX-4 ± cetuximab in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 3 TAILOR trial
Presenter: Shukui Qin
Session: Poster Display session 2
Resources:
Abstract
4481 - Undetectable RAS mutant clones in plasma: possible implication for therapy and prognosis in the patient with RAS mutant metastatic colorectal cancer?
Presenter: Mohamed Bouchahda
Session: Poster Display session 2
Resources:
Abstract
5074 - Dihydropyrimidine dehydrogenase (DPD) determination prior the administration of medicines containing fluorouracil: a single Spanish hospital experience.
Presenter: Maria Dolores Mediano Rambla
Session: Poster Display session 2
Resources:
Abstract
5242 - Differences in survival between right and left-sided colorrectal cancer (CRC) in every stage, a CARESS-CCR Group Study.
Presenter: Julia Alcaide-Garcia
Session: Poster Display session 2
Resources:
Abstract
1123 - Quality of Life (QoL) in patients with aflibercept (AFL) and FOLFIRI for metastatic colorectal cancer (mCRC) – Interim analysis with focus on mutational status of the non-interventional study QoLiTrap (AIO-LQ-0113)
Presenter: Roger von Moos
Session: Poster Display session 2
Resources:
Abstract
1212 - The cost of adverse event management in patients with RAS wild-type metastatic colorectal cancer treated with first-line cetuximab and panitumumab: an Italian healthcare payer perspective
Presenter: Karl Patterson
Session: Poster Display session 2
Resources:
Abstract
1619 - Meta-analysis of KRAS Mutation as prognostic factor in patients (pts.) with resection of colorectal (CRC) liver metastases: Tumor burden and Sideness analysis.
Presenter: Maria Romina Luca
Session: Poster Display session 2
Resources:
Abstract