Safety and efficacy of trifluridine/tipiracil in previously treated metastatic colorectal cancer: final results from the phase IIIb single-arm PRECONNECT study by duration of therapy

Background PRECONNECT was an international, phase IIIb trial evaluating the safety and efficacy of trifluridine/tipiracil (FTD/TPI) for metastatic colorectal cancer (mCRC). Methods Patients with mCRC received FTD/TPI 35 mg/m(2) twice-daily on days 1-5 and 8-12 of each 28-day cycle for third-or later-line treatment. Primary endpoint: safety and time to deterioration of Eastern Cooperative Oncology Group performance status [ECOG PS] to >= 2). Secondary endpoints included progression-free survival (PFS). Potential prognostic factors for PFS were explored.Results Of 914 patients, 69% completed 0-3, 24% completed 4-7, and 7% completed >= 8 cycles of FTD/TPI. Drug related grade >= 3 adverse events included neutropenia (38.1%), anaemia (7.2%) and asthenia (3.4%). Median [95% CI] time to ECOG PS deterioration was 8.7 [8.1-not calculable] months and increased with duration of treatment (DoT). Median PFS was 2.8 [2.7-3.0] months and increased with duration of treatment DoT. Prognostic factors associated with longer PFS included time since diagnosis of first metastasis, number of metastatic sites, baseline ECOG PS, presence/absence of liver metastasis or previous regorafenib treatment, and laboratory variables.Conclusions No new safety concerns for FTD/TPI were identified and PFS increased with DoT. These data provide confidence for the use of FTD/TPI, including the use of multiple cycles, in routine practice.

Automated summary

The PRECONNECT trial evaluated the safety and efficacy of trifluridine/tipiracil for metastatic colorectal cancer. Patients received treatment for several cycles and the study found that the time to deterioration of performance status increased with duration of treatment. The data provide confidence for the use of trifluridine/tipiracil in routine practice.