Q-TWiST Analysis Demonstrates Benefit of Fruquintinib Plus BSC in Pretreated mCRC

Sebastian Stintzing, MD

Improving survival remains a key goal for the treatment of patients with metastatic colorectal cancer (mCRC); however, ensuring patients in this population maintain quality of life (QOL) during and after treatment is also paramount, according to Sebastian Stintzing, MD.

At the 2024 Gastrointestinal Cancers Symposium, Stintzing and colleagues presented data from a post-hoc quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of the phase 3 FRESCO-2 trial (NCT04322539), which evaluated fruquintinib (Fruzaqla) plus best supportive care (BSC) vs placebo plus BSC in patients with pretreated mCRC. Findings from the analysis showed that in the fruquintinib arm, the average Q-TWiST duration was 6.25 months (95% CI, 5.89-6.61) compared with 4.21 months (95% CI, 3.81-4.60) for patients receiving placebo plus BSC (difference, 2.04 months; 95% CI, 1.51-2.57; P < .05).¹

Furthermore, the mean TWiST from randomization until disease progression without toxicity was 4.06 months (95% CI, 3.75-4.36) for the fruquintinib arm compared with 1.92 months (95% CI, 1.75-2.10) for the placebo plus BSC group (difference, 2.14 months; 95% CI, 1.78-2.49; P < .05). The average time spent experiencing grade 3/4 treatment-emergent adverse effects (TEAEs) between randomization and disease progression (TOX) was 0.45 months (95% CI, 0.37-0.53) in the fruquintinib arm and 0.21 months (95% CI, 0.15-0.28) in the placebo plus BSC arm (difference, 0.24 months; 95% CI, 0.13-0.34; P < .05).

In November 2023, the FDA approved fruquintinib for the treatment of adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. The regulatory decision was supported by prior data from FRESCO-2.²

“Fruquintinib is not only able to prolong the survival in patients with [pretreated] mCRC; it's also able to prolong the lifespan with a high quality of life,” Stintzing explained.

During an interview with OncLive^®, Stintzing discussed data from a post-hoc Q-TWiST analysis and elaborated on the importance of maintaining QOL for patients with mCRC during later lines of treatment.

Stintzing is the head of the Department of Hematology-Oncology and Cancer Immunology at the Charité Universitaetsmedizin in Berlin, Germany.

OncLive: What was the rationale for conducting a Q-TWiST analysis for FRESCO-2?

Stintzing: Fruquintinib is a selective inhibitor of all three VEGF receptors, and it has been shown in the pivotal FRESCO-2 study that it can prolong overall survival for patients with previously treated mCRC. [Fruquintinib plus BSC] has significantly prolonged progression-free survival [PFS] and overall survival [vs placebo plus BSC]

[At the 2024 Gastrointestinal Cancers Symposium], we presented a preplanned analysis of the Q-TWiST of this study. We know with this patient population [that is receiving later lines of therapy], you have the cancer and you have the treatment, which may impact QOL. Therefore, we wanted to show was, if we could prolong life, is this prolongation also meaningful for the patient? [In other words,] can you prolong life where the patient is without toxicity and without progression?

Could you expand on the methods utilized in the Q-TWiST analysis?

[The analysis included] all patients in this trial [enrolled in] the fruquintinib plus BSC [arm] vs placebo plus BSC. In a Q-TWiST analysis, you break down survival times into 3 different stages. One is [time spent with grade 3/4] toxicities for a patient [after the start of] treatment [and before disease progression]; then you have TWiST time, [meaning] time without toxicity and progression; and finally, there is relative [REL], which is the time a patient is surviving after progression.

By doing this [analysis], you can compare those times, and what we were able to show is that the TWiST times—the time without toxicity or progression—was prolonged by [2.14 months (95% CI, 1.78-2.49; P < .05) for fruquintinib vs placebo]. Therefore, [these findings] may be something you want to add when you discuss treatment options with your patients. The overall Q-TWiST time was 2.04 months (95% CI, 1.51-2.57; P <.05) longer [for fruquintinib vs placebo].

What is the known toxicity profile for fruquintinib in patients with mCRC?

Usually, fruquintinib is quite well tolerated. We [have experience with] other VEGF inhibitors, and no new toxicities were found [with fruquintinib]. Additionally, all toxicities [fruquintinib] were very manageable.

Looking into the future, what are the next steps for FRESCO-2?

We will see more data coming up in more subgroup analyses. [With the Q-TWiST] analysis, it's important to show that we are prolonging QOL for those patients who are on treatment. This [analysis] may be also interesting for regulatory agencies because they are not only looking at the sheer prolongation of survival; they [are looking to see if this] is meaningful survival, meaning without toxicity. This is exactly what we were able to show with the Q-TWiST analysis.

References

1. Stintzing S, Tabernero J, Satoh T, et al. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial. J Clin Oncol. 2024;42(suppl 3):116. doi:10.1200/JCO.2024.42.3_suppl.116
2. FDA approves fruquintinib in refractory metastatic colorectal cancer. News release. FDA. November 8, 2023. Accessed March 11, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer