Abstract 3618
Background
Advances in therapy, surgery and loco-regional procedures improved survival of patients (pts) with metastatic colorectal cancer (mCRC). Interruptions, defined Drug Holidays (DH), could reduce toxicity in pts with stable disease. We evaluated the association between DH and overall survival (OS).
Methods
754 consecutive pts treated for mCRC, at University Hospital of Udine and IRCCS CRO of Aviano from 1/1/2005 to 15/03/2017, were included. DH was defined as 56 or more consecutive days of interruption, during first line. The association of DH to OS was evaluated through uni- and multivariate Cox regression analyses. OS was estimated with Kaplan-Meier curves.
Results
Overall, 459 (60.9%) pts received continuous treatment while 255 (33.8%) a DH (5.3% missing data). After median follow-up of 68.6 months, median OS was 23.15 months. By univariate analysis, KRAS (HR 1.39; 95%CI 1.17-1.66; p < 0.001) and BRAF mutation (HR 1.39; 95%CI 1.02-1.90; p = 0.035), nodes (HR 1.92; 95%CI 1.49-2.46; p < 0.001) peritoneum (HR 1.72; 95%CI 1.38-2.15; p < 0.001), bone (HR 1.93; 95%CI 1.93; 1.02-3.64; pp = 0.043) and brain (HR 13.51; 95%CI 5.94-30.74; p < 0.001) involvement, ECOG PS (1 vs 0: HR 1.84; 95%CI 1.35-2.50,p<0.001; 2 vs 0: HR 2.87; 95%CI 1.89-4.33, p < 0.001), >1 metastatic sites (HR 1.61;95%CI 1.36-1.91; p < 0.001), DH (HR 0.43; 95%CI 0.36-0.52; p < 0.001), metastasectomy (HR 0.32; 95%CI 0.24-0.44; p < 0.001), left sidedness (HR 0.70; 95%ICI 0.58-0.86; p < 0.001), rectal tumor (HR 0.71; 95%CI 0.58-0.88; p = 0.002) and thermo-ablations (HR 0.34; 95%CI 0.25-0.47; p < 0.001) were associated with OS. In multivariate, BRAF mutation (HR 1.82; 95%CI 1.15-2.87; p = 0.010); ECOG PS 1 (HR 2.08; 95%CI 1.29-3.35; p = 0.003) and 2 (HR 3.57; 95%IC 1.91-6.63; p < 0.001) had worst prognosis. Conversely, DH (HR 0.44; 95%CI 0.35-0.57; p < 0.001), metastasectomy (HR 0.33; 95%CI 0.20-0.55; p < 0.001), thermo-ablations (HR 0.44; 95%CI 0.28-0.70; p = 0.001) and left sidedness (HR 0.72; 95%CI 0.55-0.95; p = 0.018) had better OS. Intriguingly, median OS was 35.3 months for DH and 18 months for continuous therapy.
Conclusions
DH was independently associated with better prognosis. Probably, DH is a proxy of better prognosis that clinicians intercept. Therefore, in accurately selected pts, DH can be safely offered.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Dipartimento di Oncologia, Azienda Sanitaria Universitaria Integrata di Udine.
Funding
Has not received any funding.
Disclosure
F. Puglisi: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Hoffmann-La Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre-Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.
Resources from the same session
5295 - Predictive factors and survival outcomes with stereotactic body radiation therapy in treatment of oligometastases in colorectal cancer
Presenter: Vibhay Pareek
Session: Poster Display session 2
Resources:
Abstract
5887 - Factors of importance in procuring tumoroids from colorectal liver metastasis biopsies for precision medicine.
Presenter: Lars Henrik Jensen
Session: Poster Display session 2
Resources:
Abstract
2196 - FUSAFE individual patient data meta-analysis (MA) to assess the performance of dihydropyrimidine dehydrogenase (DPD) gene polymorphisms for predicting grade 4-5 fluoropyrimidine (FP) toxicity
Presenter: Marie-Christine Etienne-Grimaldi
Session: Poster Display session 2
Resources:
Abstract
2859 - Treatments (tx) after progression to first-line FOLFOXIRI + bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and TRIBE-2 studies by GONO.
Presenter: Daniele Rossini
Session: Poster Display session 2
Resources:
Abstract
3888 - Randomized phase III study of sequential treatment with capecitabine or 5-fluorouracil (FP) plus bevacizumab (BEV) followed by the addition with oxaliplatin (OX) versus initial combination with OX+FP+ BEV in the first-line chemotherapy for metastatic colorectal cancer: The C-cubed study
Presenter: Takeshi Nagasaka
Session: Poster Display session 2
Resources:
Abstract
1065 - Early tumour shrinkage (ETS), depth of response (DpR) and associated survival outcomes in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC) classified according to Köhne prognostic category: retrospective analysis of the panitumumab (Pmab) PRIME study
Presenter: Andrea Sartore-Bianchi
Session: Poster Display session 2
Resources:
Abstract
1702 - Randomized phase II trial of CAPOX with planned oxaliplatin stop-and-go strategy as adjuvant chemotherapy after curative resection of colon cancer (CCOG-1302 study)
Presenter: Hiroyuki Yokoyama
Session: Poster Display session 2
Resources:
Abstract
5104 - A metabolomic recurrence score for risk-stratification of elderly patients (pts) with early colorectal cancer (eCRC)
Presenter: Samantha Di Donato
Session: Poster Display session 2
Resources:
Abstract
5285 - RAS mutant allele fraction in plasma predicts benefit to anti-angiogenic based first line treatment in metastatic colorectal cancer
Presenter: Giulia Martini
Session: Poster Display session 2
Resources:
Abstract
1790 - Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG
Presenter: Stephan Sahm
Session: Poster Display session 2
Resources:
Abstract