Confirmed safety and efficacy of trifluridine/tipiracil in patients with metastatic colorectal cancer
The PRECONNECT study was initiated to offer a large cohort of patients with metastatic colorectal cancer (mCRC) early access to trifluridine/tipiracil (FTD/TPI). Final results of this trial demonstrate that the safety profile of FTD/TPI is acceptable and consistent with what has been reported in the RECOURSE trial. Interestingly, both median progression-free survival (PFS) and the time to ECOG performance status deterioration increased with a longer duration of treatment with FTD/TPI.
To date, trifluridine/tipiracil (FTD/TPI) is registered in over 93 countries for the management of patients with pre-treated metastatic colorectal cancer (mCRC). In the pivotal RECOURSE study, FTD/TPI previously demonstrated a significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo. PRECONNECT is an international, multicentre, open-label, phase IIIb trial running in sixteen countries, designed to provide eligible adults with mCRC early access to FTD/TPI. In addition, the study aims at a further characterisation of the safety and efficacy of FTD/TPI in daily clinical practice. The primary endpoint of this study was safety, while secondary endpoints included PFS and quality of life.
PRECONNECT study design
Patients aged ≥18 years with histologically confirmed mCRC who were refractory to, or ineligible for, standard chemotherapy and with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, were treated with oral FTD/TPI 35 mg/m2 twice-daily on days 1-5 and 8-12 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, physician decision, withdrawal of consent, pregnancy, major protocol deviation, or when FTD/TPI became commercially available. Of the 914 patients in the per protocol population, 632 (69%) completed 0-3 cycles, 219 (24%) completed 4-7 cycles and 63 (7%) completed at least eight cycles of FTD/TPI. Median relative dose intensities were 92.8%, 86.2% and 83.3%, respectively. Interestingly, compared to patients who completed only 0–3 cycles of FTD/TPI, those who completed 4-7 and ≥8 cycles were significantly more likely to have a baseline ECOG PS of 0 (p= 0.0004), were less likely to have a RAS mutation (p= 0.0378) and had a longer time (≥18 months) from first metastasis to first FTD/TPI intake (p=0.0014).
Safety and efficacy of FTD/TPI
Overall, the safety of FTD/TPI was in line with previous reports without any new signals. Treatment-emergent adverse events (TEAEs) were experienced by 96.6% of the overall patient population. The most commonly reported TEAEs of grade ≥3 consisted of neutropenia (38.8%), anaemia (11.3%), asthenia (5.4%) and diarrhoea (4.3%). Severe febrile neutropenia (1.2%) and severe cardiac disorders (0.7%) were infrequent. Importantly, the safety profile of of FTD/TPI was consistent regardless of DoT.
The median PFS in the overall population was 2.8 months and increased with a longer DoT. In fact, it was only 2.2 months for patients who received 0-3 cycles, increasing to 5.3 months for patients who received 4-7 and to 9.4 months for those who were treated with at least eight cycles. Similarly, also the disease control rate increased with a longer treatment duration at 12.3% to 75.3% and 96.8% for patients receiving 0-3, 4-7 or ≥8 treatment cycles, respectively. Finally, also time to ECOG PS deterioration increased with DoT with FTD/TPI (0-3 cycles: 3.6 months, 4-7 cycles: 8.9 months, ≥8 cycles: 16.4 months).
PRECONNECT data in daily clinical practice reflect the safety and efficacy findings of FTD/TPI reported in the phase III RECOURSE study. Interestingly, the PFS and disease control rate gradually improved with a higher number of FTD/TPI treatment cycles. Similarly, also the time to deterioration of patient performance was increased with an increasing duration of FTD/TPI treatment. As such, these data provide further reassurance on the use of FTD//TPI in routine treatment of patients with mCRC.
Taieb J, et al. Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in previously treated metastatic Colorectal cancer (mCRC): final results according to duration of treatment from the phase IIIb, international, open-label, early-access PRECONNECT study. Presented at 2021 ESMO World Congress on Gastrointestinal Cancer; Abstract SO-18.