Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

Abstract

Background: In RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil.

Methods: In this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL).

Results: 793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03-14.72). There was no clinically relevant change from baseline in QoL.

Conclusions: PRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment.

Trial registration number: NCT03306394.

Keywords: colorectal cancer; metastatic; quality of life; safety; trifluridine tipiracil.

Conflict of interest statement

Competing interests: J-BB received consulting fees and lecture fees from Amgen, Bayer, Merck Serono, and Servier and lecture fees from Celgene, Roche, and Sanofi. LW has received honoraria for consulting or advisory roles from Servier and Halozyme, has served on a Speakers Bureau for Amgen and holds patents, royalties or intellectual project from Cervico. TP has received compensation for advisory board for Amgen (paid self), Merck, Roche and Takeda (paid self). CC has received honoraria from Amgen, Bayer, Merck, Roche and Servier and research grants from Merck. J-MP has received advisory role or research grants from Roche, Merck, Amgen, Sanofi, Bayer and Servier. FP has received advisory role or research grants from Sanofi, Ipsen, MSD and Servier. AO received research funding from Servier, Astra Zeneca, Roche, Bayer, Novartis, Gen Pharmacy and PPD and received support to attend congresses from Roche, Novartis, Abdi İbrahim, Koçak, Takeda, Astellas, Bayer, Servier, Onko Koçsel, Jansen, BMS and Pfizer. IC has received honoraria for speaker or advisory role from Servier, Roche, Bayer, Amgen, Astra Zeneca, MSD, Pfizer, Novartis and Lilly. DA, MB, LV, and NM are employees of Servier. EVC has received grants from Amgen, Bayer, BMS, Boehringer, Celgene, Ipsen, Lilly, Merck, MSD, Novartis, Roche and Servier and honoraria from Bayer, BMS, Celgene, Lilly, Novartis and Servier. JT has received honoraria for speaker or advisory role from Servier, Roche, Lilly, Celgene, Shire, Amgen, Sanofi, Merck, Lilly and Sirtex. AF has received compensation for participation to advisory boards and research grants to his institution from Amgen, Bayer, Merck, MSD, Roche, Lilly, Servier and Bristol.

© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.

Figures

Figure 1

Management of (A) haematological and (B) non-haematological adverse events. §Resumption criteria are ≥1.5 × 109/L for neutrophils and ≥75 × 109/L for platelets. *Dose reductions are permitted to a minimum dose of 20 mg/m2/dose twice daily; dose increase is not permitted after dose reduction.

Figure 2

(A) PFS (n=793*) and (B) time to Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or higher (n=793†). *Two patients were censored from the analysis because they received another anticancer therapy after withdrawal from the study drug and no postbaseline efficacy evaluation was performed. †Although baseline ECOG PS data were not collected for 24 patients, data were collected at subsequent visits so these patients were included in the analysis. PFS, progression-free survival.

Figure 3

Change from baseline across cycles in the EORTC QLQ-C30 Global Health Status score. Data are mean±SD. Patient numbers refer to patients with evaluable questionnaires/total number of patients still on treatment. EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire.