Trifluridine/tipiracil, regorafenib, or supportive therapy? Factors affecting the success of mCRC treatment
Currently, there are no biomarkers available to help decide, for a specific patient with refractory metastatic colorectal cancer (mCRC), whether therapy with trifluridine/tipiracil or regorafenib will be more effective and which patients will benefit the most from the treatment. A group of Czech oncologists presented the results of their analysis on this topic at the Gastrointestinal Symposium of the American Society of Clinical Oncology (ASCO) held in January 2020 in San Francisco.
Therapeutic options for refractory mCRC
Both trifluridine/tipiracil (TAS-102) and regorafenib are indicated for patients with refractory mCRC; however, their efficacy is relatively low. In Phase III clinical trials, a statistically significant but very small improvement in progression-free survival (PFS) was observed in these patients compared to placebo (2.0 vs. 1.7 months for TAS-102 and 1.9 vs. 1.7 months for regorafenib).
Currently, no validated biomarkers are available to predict therapy efficacy for individual patients. The presented analysis of real-world clinical practice data therefore investigated predictive and prognostic factors of therapy efficacy in 212 patients with refractory mCRC treated at four Czech oncology centers.
Parameters evaluated in the analysis
A retrospective and prospective analysis of clinical data was conducted on 132 patients treated with TAS-102, 52 patients using regorafenib, and 28 patients who were sequentially treated with both agents. Several factors related to PFS and overall survival (OS) were evaluated: line of treatment, number and location of metastatic sites, location of primary tumor, mutational status, time since diagnosis, prior treatments, discovery of metastases, laboratory tests, and adverse treatment effects.
Findings
The median follow-up period was 16.5 months, and patients had undergone an average of three therapeutic regimens before study treatment. The median OS and PFS for patients treated with TAS-102 were 10.2 and 3.3 months, respectively, while for those treated with regorafenib it was 6.9 and 2.8 months, respectively.
Factors significantly associated with longer OS for the entire cohort included:
- ≥ 24 months since mCRC diagnosis
- ≥ 3 months since the last therapy (fluoropyrimidine cytostatic for TAS-102 and anti-VEGF agent for regorafenib)
- Performance status (PS) per ECOG = 0 (fully active patient)
- White blood cell count at treatment initiation < 8 × 109/l
- Normal CRP at treatment initiation
Based on factors statistically significantly related to overall treatment success, the authors proposed a TASREG scoring system that assigns one point for each risk characteristic derived from the above list.
According to the TASREG system, patients were categorized into high-risk (0–1 point; OS of 4.6 months), medium-risk (2–3 points; OS of 7.9 months), and favorable prognosis (> 4 points; OS of 11.8 months). Differences in PFS were also significant according to this system.
Specifically for TAS-102 therapy, the occurrence of grade ≥ 2 neutropenia was related to treatment success. Factors affecting the success of regorafenib therapy included normal lactate dehydrogenase (LDH) levels, no liver metastases, and asynchronous disease.
Conclusion
The TASREG score can identify a group of pretreated mCRC patients who will benefit most from further therapy with TAS-102 or regorafenib. For patients with high risk, quality symptomatic and supportive therapy may be more beneficial. TAS-102 appeared to be slightly more effective than regorafenib in the analysis, but it is a non-randomized retrospective study.
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Source: Grell P., Bořilová S., Schwanzerová R. et al. Factors associated with effectiveness of trifluridine/tipiracil versus regorafenib in patients with pretreated metastatic colorectal cancer (mCRC). J Clin Oncol 2020; 38 (Suppl. 4): 137, doi: 10.1200/JCO.2020.38.4_suppl.137.
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