RETRO-TAS Study – Trifluridine/Tipiracil in Pretreated mCRC in Real-World Practice

FTD/TPI in Key Studies

Trifluridine/tipiracil is indicated for adult patients with refractory mCRC who have used chemotherapy regimens based on fluoropyrimidine, oxaliplatin, or irinotecan and anti-VEGF or anti-EGFR antibodies. Its safety and efficacy were demonstrated in phase II studies (Yoshino et al.), on the basis of which it was approved in Japan, followed by the phase III RECOURSE study, which became the basis for its registration in the USA (2015) and Europe (2016). The results of these studies were confirmed by the recent phase IIIb PRECONNECT evaluation.

RETRO-TAS – Real-World Insights

Study Population and Parameters Evaluated

The RETRO-TAS study retrospectively analyzed data of mCRC patients after ≥ 2 previous lines of treatment who received FTD/TPI based on physician decision in 8 oncology centers in Greece. The authors used data of patients older than 18 years who had histologically confirmed disease and available data on previous lines of chemotherapy and used FTD/TPI at the approved dose (35 mg/m² p.o. twice daily on days 1–5 and 8–12 of each 28-day therapy cycle). From October 2018 to October 2021, 200 patients with a median age of 63.7 years at diagnosis and 67.0 years at the start of FTD/TPI treatment were included.

The authors evaluated clinicopathological indicators of mCRC (molecular profile, primary tumor sidedness), treatment duration, dose adjustments, and toxicity. They also calculated median progression-free survival (PFS) and overall survival (OS), the percentage of patients with PFS at 6 and 8 months, the objective response rate, and the disease control rate.

Results

At the time of analysis, the median follow-up duration was 14 months, with 158 cases of disease progression and 106 deaths recorded. Adjuvant chemotherapy was undertaken by 39.5% and radical surgery by 51.5% of the subjects. FTD/TPI was administered in the 3rd (70.5%), 4th (17.0%), or 5th (12.5%) line of treatment, mostly as monotherapy (71.5%), with some patients receiving it in combination with the anti-VEGF antibody bevacizumab (24.5%) and rarely with the anti-EGFR antibody (4.0%).

The median duration of therapy was 119.5 days, with 81% of patients discontinuing due to disease progression. Complete remission was achieved in 0.5% of patients, partial remission in 25%, disease stabilization in 20%, and progression in 47% (results were not evaluable for 7.5% of participants). The median PFS was 4.8 months, and the median OS was 11.4 months. Six-month PFS was achieved by 41.4%, and eight-month PFS by 31.5%. Multivariate analysis showed a negative correlation of survival with performance status (PS) > 1 and the presence of liver and lung metastases. Tumor sidedness and mutation status were not correlated with survival.

Severe adverse events reported included neutropenia (4 patients), anemia (2), thrombocytopenia (1), diarrhea (1), nausea (1), and fatigue (8 patients). Dose reduction was necessary in 25% of patients, delay of the next cycle in 31%, and shorter treatment duration in 14.5%.

Conclusion

This observational study from real-world Greek practice confirms the conclusions of the phase III RECOURSE controlled study and provides further evidence of the benefit of FTD/TPI in ≥ 3rd line treatment of mCRC in all patient subgroups regardless of mutation status and primary tumor sidedness.

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Source: Koumarianou A., Ntavatzikos A., Vourli G. et al. P-50 RETRO-TAS, a retrospective observational study of trifluridine/tipiracil in chemorefractory metastatic colorectal cancer. ESMO World Congress on Gastrointestinal Cancer 2022. Available at: www.esmo.org/meeting-calendar/past-meetings/esmo-world-congress-on-gastrointestinal-cancer-2022