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
1109 - First Canadian Interim Analysis from the Phase IIIb CompLEEment-1 Ribociclib + Letrozole HR+ HER2- Advanced Breast Cancer Trial
Presenter: Cristiano Ferrario
Session: Poster Display session 2
Resources:
Abstract
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract