Introduction: The RECOURSE trial demonstrated a modest benefit in overall survival (OS) for trifluridine/tipiracil (FTD/TPI) versus placebo in pretreated metastatic colorectal cancer (mCRC) patients. Unfortunately, quality of life (QoL) was not assessed. We evaluated QoL and survival of patients treated with FTD/TPI in daily practice. Patients and Methods: QUALITAS is a substudy of the Prospective Dutch CRC cohort (PLCRC). From 150 mCRC patients treated with FTD/TPI, QoL (EORTC QLQ-C30 and QLQ-CR29) was assessed monthly from study entry, and linked to clinical data of the Netherlands Cancer Registry. Joint models were constructed combining mixed effects models with Cox PH models. Primary endpoint was difference in QoL over time (which was deemed clinically relevant if ≥10 points). Secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), and OS. We analyzed the association between QLQ-C30 Summary Score (QoL-SS) at FTD/TPI initiation (baseline) and survival. Results: There was no clinically relevant change in QoL-SS from baseline to 10 months post-baseline (i.e. the cut-off point after which 90% of patients had discontinued FTD/TPI treatment): -5.3 [95% CI -8.7;-1.5]. Patients who were treated with FTD/TPI for ≥ 3 months (n = 85) reported 6.3 [1.6;11.1] points higher baseline QoL, compared to patients treated < 3 months (n = 65, “poor responders”). In the latter, time to a clinically relevant QoL deterioration was < 2 months. Median PFS, TTF and OS were 2.9 [2.7;3.1], 3.1 [2.9;3.2] and 7.7 [6.6;8.8] months, respectively. Worse baseline QoL-SS was independently associated with shorter OS (HR 0.45 [0.32;0.63]), PFS (0.63 [0.48;0.83]), and TTF (0.64 [0.47;0.86]). Conclusion: The maintenance of QoL during FTD/TPI treatment in daily practice supports its use. The QoL deterioration in “poor responders” is likely due to disease progression. The strong association between worse baseline QoL and shorter survival suggests that clinicians should take QoL into account when determining prognosis and treatment strategy for individual patients.
Bibliographical noteFunding Information:
This study was funded by a grant from Servier Netherlands Farma B.V.
GRV reports research grants/funding paid to her institution by Servier, BMS, Bayer, Merck, PGDx, and Sirtex. GRV reports travel/accommodation fees from Servier. CJAP reports his advisory role for Nordic Pharma. MK reports personal travel/accommodation fees from Congress Care-Dutch oncology society (NVMO). MK reports research grants/funding paid to her institution by Amgen, Bayer, BMS, Merck-Serono, Nordic Pharma, Roche, Servier, Sirtex, and Sanofi-Aventis. MK reports honoraria paid to her institution by BMS, Nordic Pharma, and Servier. MK reports the following nonfinancial interests: an advisory role for ZON-MW, membership of the scientific board of the Dutch Cancer Society (KWF), chairmanship of the Dutch Colorectal Cancer Group (DCCG), principal investigator (PI) of the Prospective Dutch CRC Cohort (PLCRC), involvement in several clinical trials as PI or co-investigator in colorectal cancer. AMM reports advisory fees from Novartis paid to her institution. JdV has served as a consultant for Amgen, AstraZeneca, MSD, Pierre Fabre, and Servier, and has received institutional research funding from Servier (all outside the submitted work). All remaining authors have declared no conflicts of interest.
The authors would like to thank all participating patients and the staff of the 26 participating hospitals. The authors also thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry as well as IKNL staff for scientific advice. We gratefully acknowledge Maaike Koelink (PLCRC) for her contribution to the data collection, and Britt Tuerlings MSc (PROFILES) for her support during the data collection and data cleaning stages. We are indebted to René Eijkemans PhD for his help in predicting survival for varying baseline Summary Scores taking into account non–proportionality. This study was supported by the Dutch Colorectal Cancer Group (DCCG).