FRESCO-2 results: Subgroup analyses reveal prolonged survival in mCRC study
Who benefits most from fruquintinib in metastatic colorectal cancer? A subgroup analysis of the FRESCO-2 study focuses on individuals with long overall survival.
FRESCO-2 in brief – the framework for subgroup analysis
In the global, randomised Phase III FRESCO-2 study, fruquintinib was tested in heavily pretreated patients with mCRC against placebo, each in combination with best supportive care (2:1 randomisation; 5 mg p.o. daily; three weeks of treatment followed by a one-week break per cycle). This showed a significant survival benefit for the fruquintinib cohort in terms of overall survival and progression-free survival compared to the control arm:
- The risk of death was reduced (HR 0.66); after 6 months, 60.4% of patients receiving fruquintinib were still alive compared to 41.5% receiving placebo, and after 9 months, 41.1% vs. 28.2%.
- After 6 months, 23.8% of patients on fruquintinib had no disease progression, compared with 1.1% on placebo. After 9 months, the figures were 11.3% vs. 0.5%.
Approximately one quarter of patients achieved ≥ 10 months overall survival
Of 461 individuals in the fruquintinib arm, 113 (24.5%) lived for at least 10 months (10.0–18.9 months). These patients were naturally exposed for longer (median treatment duration 6.3 months vs. 3.1 in the overall fruquintinib cohort) and received more cycles (median 7 vs. 3).
No liver metastases and ECOG 0
The subanalysis suggests that certain baseline characteristics are associated with longer survival. Patients who achieved an overall survival of ≥ 10 months on fruquintinib had fewer liver metastases and a better general condition (measured by ECOG score) at the start of the study compared to the entire fruquintinib cohort:
- Specifically, 41.6% of this subgroup were free of liver metastases (total fruquintinib population: 26.5%).
- In addition, 54.0% of this group started treatment with ECOG 0, compared with 42.5% in the total fruquintinib group.
These differences correspond to a more than 10 percentage point higher proportion of patients without liver metastases or with optimal general condition in the subgroup with overall survival ≥ 10 months. Other baseline parameters (e.g. primary tumour location, number of prior therapies) were similarly distributed between the two populations.
Safety profile during prolonged treatment
In terms of tolerability, the group with overall survival ≥ 10 months did not differ significantly from the overall fruquintinib cohort: the proportion of serious (grade ≥ 3) treatment-related adverse events was comparable (61.9% vs. 62.7%).
However, dose adjustments were required more frequently with longer treatment duration (95.6% vs. 70.8%), while side effects led to discontinuation of therapy less frequently (14.2% vs. 20.4%). Adverse events of special interest (AESI) were reported more frequently (94.7% vs. 80.7%).
Overall, the data show no new safety signals and indicate a consistent safety profile during longer treatment.
Conclusion
The evaluation of the FRESCO-2 data shows that a significant proportion of patients with mCRC can achieve longer-term survival with fruquintinib. 24.5% of those treated lived for 10 months or longer, with individuals in this subgroup more likely to start therapy in good general condition and without hepatic metastasis.
At the same time, the safety profile of fruquintinib remained unchanged and no new side effects occurred with longer-term use. However, adjustments are more frequently required with prolonged exposure. The subanalysis thus provides valuable insights for identifying patients who benefit particularly from fruquintinib.
- Kasper S, Sartore-Bianchi A, Randrian V, Cremolini C, Arnold D, Dasari A, Eng C, Lonardi S, Elez E, Yoshino T, Sobrero AF, Yao JC, Hochster HS, Van Cutsem E, Tougeron D, Yu Z, Dong Q, Schelman WR, Ghiringhelli F. Fruquintinib plus best supportive care for patients with metastatic colorectal cancer: characterization of patients who had an overall survival of ≥10 months in the FRESCO-2 study. Poster P875. Presented at the DGHO (German Society for Hematology and Oncology) Annual Meeting, 24–27 October 2025, Cologne, Germany.