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Clinical Trial
. 2019 Jun 3;19(1):533.
doi: 10.1186/s12885-019-5753-7.

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

A Carrato  1 , M Benavides  2 , B Massutí  3 , R Ferreiro-Monteagudo  4 , P García Alfonso  5 , E Falcó  6 , M Reboredo  7 , T Cano  8 , J Gallego  9 , J M Viéitez  10 , L Layos  11 , A Salud  12 , E Polo  13 , E Dotor  14 , G Durán-Ogalla  2 , M Rodriguez-Garrote  4 , A Calvo  5 , E Grande  4 , E Aranda  8
Affiliations
Clinical Trial

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

A Carrato et al. BMC Cancer. .

Abstract

Background: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC.

Methods: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features.

Main objective: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest).

Results: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%).

Conclusions: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach.

Trial registration: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.

Keywords: Colorectal cancer; Elderly; First-line; Frail patients; Monotherapy; Regorafenib.

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Conflict of interest statement

Viéitez has received honoraria for advisory activities from Bayer. Grande has received research fundings from Bayer, Astellas, Pfizer and AstraZeneca. Aranda has received honoraria for advisory role from Amgen, Bayer, Celgene, Merck, Roche and Sanofi. Carrato has received honoraria for advisory activities from Bayer, Pfizer, Merck and Shire. The other authors have stated that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Progression free survival and Overall survival
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References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262. - DOI - PubMed
    1. van der Pool AEM, Damhuis RA, Ijzermans JNM, de Wilt JHW, Eggermont AMM, Kranse R, et al. Trends in incidence, treatment and survival of patients with stage IV colorectal cancer: a population-based series. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2012;14(1):56–61. - PubMed
    1. van der Geest LGM, J’t L-B, Koopman M, Verhoef C, MAG E, de JHW W. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis. 2015;32(5):457–465. doi: 10.1007/s10585-015-9719-0. - DOI - PubMed
    1. Fulop T, Larbi A, Witkowski JM, McElhaney J, Loeb M, Mitnitski A, et al. Aging, frailty and age-related diseases. Biogerontology. 2010;11(5):547–563. doi: 10.1007/s10522-010-9287-2. - DOI - PubMed
    1. Lang P-O, Michel J-P, Zekry D. Frailty syndrome: a transitional state in a dynamic process. Gerontology. 2009;55(5):539–549. doi: 10.1159/000211949. - DOI - PubMed

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