3618 - Drug holidays and overall survival in patients treated for metastatic colorectal cancer

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.