Real-world (RW) treatment patterns and clinical outcomes of patients treated with sequential regorafenib and trifluridine/tipiracil ± bevacizumab (BEV) for metastatic colorectal cancer (mCRC) in the United States (US) community oncology setting: The SEQRT2 study.
Authors: Bekaii-Saab Tanios S. , Cosgrove David , Sruti Ila , Shi Junxin , Dai Wei , Patton Gregory Alan , Appukkuttan Sreevalsa , Hocum Brian Thomas , Katta Arvind , Earl Jacob , Babajanyan Svetlana , Barzi Afsaneh 
Published: January 2025

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Background:
Both Regorafenib (R) and Trifluridine/Tipiracil (T) ± BEV are widely used treatments for mCRC in later lines. This RW study evaluated optimal sequencing and associated outcomes among patients who initiated R and T in sequential lines of therapy (LOT) between LOT1-LOT6 within community oncology settings in the US.
Methods:
A retrospective study utilizing electronic medical record data from The US Oncology Network examined adult patients with mCRC who initiated R and T ± BEV sequentially between 09/01/2015 and 11/30/2022 (index date), with follow-up until 05/31/2023. Treatment patterns, overall survival (OS) and time to next treatment (TTNT) after sequence were assessed overall, R first (R-T) and T first (T-R). Multivariable Cox regression adjusting for age, sex, ECOG, tumor stage, and prior medication, assessed the association of factors with OS and TTNT.
Results:
In total, 308 mCRC patients initiating R and T (R-T, 156 pts [140 R-T and 16 R-T+BEV]; T-R, 152 pts [136 T-R and 16 T+BEV-R]) met study criteria. Baseline demographic (mean age 63 yrs, males 55%) and clinical characteristics (70% colon cancer, 58% ECOG 0-1) were similar between the cohorts. Most patients initiated index therapies at the third line of therapy (LOT3) (49% R-T, 45% T-R). The median (IQR) sequence duration was 7.4 (5.6), 6.7 (4.4), and 7.0 (4.7) months, respectively in patients with R-T, T-R, and overall. The median (95% CI) OS was 12.8 (11.2, 14.1) months among R-T and 10.2 (8.8, 11.9) months among T-R patients. Compared to R-T, the adjusted HR for the T-R sequence was 1.2 (95% CI 0.9–1.6; p=0.2). The median (95% CI) TTNT was 9.3 (8.4, 10.3) and 8.6 (7.8, 9.4) months, for R-T and T-R, respectively; the adjusted HR was 1.1 (95% CI 0.8–1.4; p=0.62).
Conclusions:
Patients initiating R first appeared to have a longer duration of treatment and survival, although not statistically significant. The one-year median duration of survival in this real-world setting confirms the importance of access to these treatments in patients with mCRC and can inform physicians regarding the choice of medications while sequencing therapies in mCRC.

Clinical outcomes among R-T and T-R mCRC patients.

Variable
Level

R-T (± BEV)[N
1
= 156]

T (± BEV) -R[N
1
= 152]

Adjusted
3,4
HR
5
(95% CI)[R-T Reference]

Effect

OverallSurvival
Months – median (95% CI)
12.8(11.2, 14.1)
10.2(8.8, 11.9)

1.20 (0.91, 1.58)

0.20

TTNT
2

Months – median (95% CI)
9.3(8.4, 10.3)
8.6(7.8, 9.4)

1.07 (0.83, 1.37)

0.62

1
Entire R-T and T-R cohorts are presented since 16 patients in each cohort initiated T+BEV.

2
Time To Next Treatment.

3
Overall Survival adjusting for age, gender, stage at diagnosis, ECOG, prior anti-VEGF treatment.

4
Time To Next Treatment adjusting for age, gender, stage at diagnosis, and line of therapy.

5
Hazard Ratio.