Discussion
tumour, neutropenia
TUMOUR, NEUTROPENIA
The final results from the PRECONNECT study in patients with mCRC in daily clinical practice confirm the interim data published in 2020 [There is a lack of information on potential prognostic factors in later lines of treatment in patients with mCRC. In patients naïve to chemotherapy treatment, CEA, number of metastatic sites, age, NLR, lactate dehydrogenase levels, and primary tumour location, have been shown to be important prognostic indicators [In addition, median PFS was longer in patients experiencing neutropenia or severe neutropenia during FTD/TPI treatment (and importantly, most neutropenia occurred during the first three cycles of FTD/TPI treatment and this frequency during the first three cycles was higher in patients who went on to have a longer DoT [data not shown]). These results were expected as higher exposure of patients with mCRC increases the risk of neutropenia, and hence, patients developing neutropenia have improved OS and PFS [Limitations of PRECONNECT include the lack of a comparator arm and the lack of follow-up data which meant that OS was not assessed. One of the reasons OS could not be assessed was the withdrawal criterion of FTD/TPI commercial availability, which accounted for 10% of all withdrawals. However, this is unlikely to have an impact on the other conclusions from the study due to the relatively large study population recruited from 16 countries, which helps to define the safety of FTD/TPI more broadly than is possible with controlled clinical trials. As PRECONNECT was a ‘real-world’ study, follow-up assessments were based on the standard of care at each centre; this meant that, for example, the date of assessment of response may have varied in the recruited population (e.g., it could be 2 months at one centre and 3 months at another), which would have an impact on the PFS outcomes.In summary, findings from the PRECONNECT study (which, with 914 patients, constitutes the largest real-world cohort of patients receiving FTD/TPI to date) lend additional support and confidence for the routine use of FTD/TPI, including the use of multiple cycles, for the treatment of patients with mCRC in daily clinical practice. The results demonstrate that neutropenia is a potential predictor of response in the real-world setting. Median time to ECOG PS deterioration was 8.7 months, median PFS was 2.8 months and both increased with duration of treatment. Our understanding of the efficacy and safety of FTD/TPI stem largely from the pivotal RECOURSE clinical trial – PRECONNECT enhances our understanding of the safety and efficacy in the real-world and when FTD/TPI is used over longer durations.