Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal cancer: real-life data from The Netherlands

International Journal of Clinical Oncology, Dec 2017

Background The RECOURSE trial showed clinical efficacy for trifluridine/tipiracil for refractory metastatic colorectal cancer patients. We assessed the feasibility and effectiveness of trifluridine/tipiracil in daily clinical practice in The Netherlands. Methods Medical records of patients from 17 centers treated in the trifluridine/tipiracil compassionate use program were reviewed and checked for RECOURSE eligibility criteria. Baseline characteristics, safety, and survival times were compared, and prespecified baseline characteristics were tested in multivariate analyses for prognostic significance on overall survival (OS). Results A total of 136 patients with a median age of 62 years were analyzed. Forty-three patients (32%) did not meet the RECOURSE eligibility criteria for not having received all prior standard treatments (n = 35, 26%) and/or ECOG performance status (PS) 2 (n = 12, 9%). The most common grade ≥3 toxicities were neutropenia (n = 44, 32%), leukopenia (n = 8, 6%), anemia (n = 7, 5%), and fatigue (n = 7, 5%). Median progression-free survival (PFS) and median OS were 2.1 (95% CI, 1.8–2.3) and 5.4 months (95% CI, 4.0–6.9), respectively. Patients with ECOG PS 2 had a worse median OS (3.2 months) compared to patients with ECOG PS 0–1 (5.9 months). ECOG PS, KRAS-mutation status, white blood cell count, serum lactate dehydrogenase, and alkaline phosphatase were prognostic factors for OS. Conclusions Our data show that treatment with trifluridine/tipiracil in daily clinical practice is feasible and safe. Differences in patient characteristics between our population and the RECOURSE study population should be taken into account in the interpretation of survival data. Our results argue against the use of trifluridine/tipiracil in patients with ECOG PS 2. Funding Johannes J.M. Kwakman received an unrestricted research grant from Servier.

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Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal cancer: real-life data from The Netherlands

International Journal of Clinical Oncology https://doi.org/10.1007/s10147 Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal cancer: real‑life data from The Netherlands 0 Johannes J. M. Kwakman 1 Department of Medical Oncology, Maastricht University Medical Center , P. Debyelaan 25, 6229 HX Maastricht , The Netherlands 2 Department of Medical Oncology, Elisabeth-TweeSteden Hospital , Doctor Deelenlaan 5, 5042 AD Tilburg , The Netherlands 3 Department of Medical Oncology, University Medical Center Utrecht , Heidelberglaan 100, 3584 CX Utrecht , The Netherlands 4 Department of Medical Oncology, Martini Hospital , Van Swietenplein 1, 9728 NT Groningen , The Netherlands 5 Department of Medical Oncology, Catharina Hospital , Michelangelolaan 2, 5623 EJ Eindhoven , The Netherlands 6 Department of Medical Oncology, The Netherlands Cancer Institute , Plesmanlaan 121, 1066 CX Amsterdam , The Netherlands Background The RECOURSE trial showed clinical efficacy for trifluridine/tipiracil for refractory metastatic colorectal cancer patients. We assessed the feasibility and effectiveness of trifluridine/tipiracil in daily clinical practice in The Netherlands. Methods Medical records of patients from 17 centers treated in the trifluridine/tipiracil compassionate use program were reviewed and checked for RECOURSE eligibility criteria. Baseline characteristics, safety, and survival times were compared, and prespecified baseline characteristics were tested in multivariate analyses for prognostic significance on overall survival (OS). Results A total of 136 patients with a median age of 62 years were analyzed. Forty-three patients (32%) did not meet the RECOURSE eligibility criteria for not having received all prior standard treatments (n = 35, 26%) and/or ECOG performance status (PS) 2 (n = 12, 9%). The most common grade ≥3 toxicities were neutropenia (n = 44, 32%), leukopenia (n = 8, 6%), anemia (n = 7, 5%), and fatigue (n = 7, 5%). Median progression-free survival (PFS) and median OS were 2.1 (95% CI, 1.8-2.3) and 5.4 months (95% CI, 4.0-6.9), respectively. Patients with ECOG PS 2 had a worse median OS (3.2 months) compared to patients with ECOG PS 0-1 (5.9 months). ECOG PS, KRAS-mutation status, white blood cell count, serum lactate dehydrogenase, and alkaline phosphatase were prognostic factors for OS. Conclusions Our data show that treatment with trifluridine/tipiracil in daily clinical practice is feasible and safe. Differences in patient characteristics between our population and the RECOURSE study population should be taken into account in the interpretation of survival data. Our results argue against the use of trifluridine/tipiracil in patients with ECOG PS 2. Funding Johannes J.M. Kwakman received an unrestricted research grant from Servier. Trifluridine/tipiracil; TAS-102; Metastatic colorectal cancer; Compassionate use; Feasibility Introduction Recently, trifluridine/tipiracil (TAS-102) has shown efficacy in refractory metastatic colorectal cancer (mCRC). The randomized phase 3 RECOURSE trial showed a significant increase in median overall survival (OS) of 1.8 months compared to placebo in refractory mCRC patients [ 1 ]. Trifluridine is a thymidine analogue that is incorporated into DNA, causing its antitumor effect [ 2 ]. Tipiracil hydrochloride prevents the rapid degradation of trifluridine, which allows for continuous adequate plasma levels of trifluridine [ 3, 4 ]. Extended author information available on the last page of the article Clinical trial results provide the backbone of evidencebased medicine and are incorporated in clinical guidelines. However, a trial population may not always be a representative sample of the total population because of restrictive trial eligibility criteria. For example, in the RECOURSE study only patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 were included. Also, the controlled conditions under which clinical trials are usually performed cannot always be guaranteed in general practice. Hence, the use of observational data of nontrial patients may be helpful to assess the feasibility and effectiveness of novel treatments in daily clinical practice. After publication of the results of RECOURSE [ 1 ], a compassionate use program for trifluridine/tipiracil in refractory mCRC patients was initiated in The Netherlands before market access January 2017. We analyzed the baseline characteristics of these patients with the RECOURSE eligibility criteria and assessed the feasibility and effectiveness of trifluridine/tipiracil treatment in this non-trial population. Finally, these data allowed us to evaluate patient and tumor characteristics for prognostic significance on OS. Methods Patients Physicians who registered patients between December 2015 and January 2017 for the trifluridine/tipiracil compassionate use program in The Netherlands were invited to participate in the study. Participation criter (...truncated)


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Johannes J. M. Kwakman, G. Vink, J. H. Vestjens, L. V. Beerepoot, J. W. de Groot, R. L. Jansen, F. L. Opdam, H. Boot, G. J. Creemers, J. M. van Rooijen, M. Los, A. J. E. Vulink, H. Schut, E. van Meerten, A. Baars, P. Hamberg, E. Kapiteijn, D. W. Sommeijer, C. J. A. Punt, M. Koopman. Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal cancer: real-life data from The Netherlands, International Journal of Clinical Oncology, 2017, pp. 1-8, DOI: 10.1007/s10147-017-1220-0