Real-world treatment patterns and outcomes among patients initiating SEQuential Regorafenib and Trifluridine/Tipiracil+/-bevacizumab in patients with metastatic colorectal cancer in a US community setting (SEQRT2)

Tanios Bekaii-Saab¹Ila Sruti^2*Junxin Shi²Wei Dai²Gregory Patton²Sreevalsa Appukkuttan³Brian Hocum³Arvind Katta³Svetlana Babajanyan³David Cosgrove⁴

• ¹Mayo Clinical Cancer Center, Phoenix, United States
• ²Real World Research, Ontada, Boston, United States
• ³Bayer Healthcare Pharmaceuticals Inc., Whippany, United States
• ⁴Compass Oncology, Vancouver, Washington, United States

Background: Regorafenib and trifluridine/tipiracil (FTD/TPI) +/- bevacizumab are both indicated for patients diagnosed with metastatic colorectal cancer (mCRC) in third-line or later. However, in the absence of recommendations regarding preferred treatment order, our study aimed to improve the understanding of real-world optimal treatment sequence. Methods: This retrospective study assessed real-world outcomes and treatment patterns among mCRC patients that initiated sequential regorafenib and FTD/TPI +/- bevacizumab between first-line and sixth-line from September 2015 to November 2022 in The US Oncology Network. Patient and treatment characteristics were assessed descriptively, overall and stratified by treatment order. Kaplan-Meier methods were used for time-to-event endpoints, including real-world overall survival (rwOS), real-world progression free survival (rwPFS), and real-world time to next treatment (rwTTNT) following sequence. Endpoints were also evaluated with Cox proportional hazard models. Results: This study examined 308 patients initiating sequential regorafenib and FTD/TPI, 156 patients initiating regorafenib first (R-T) and 152 patients initiating FTD/TPI first (T-R). Demographic and clinical characteristics were similar across cohorts. The population was predominately male, had a mean age of 63 years, and colon primary at diagnosis. The median rwOS was numerically longer among the R-T cohort compared to the T-R cohort (12.8 [11.2,14.1] vs. 10.2 [8.8,11.9] months). The median rwPFS was similar (3.4 [3.0, 3.6] vs. 3.4 [3.0,3.7 months) for both the R-T and T-R cohorts. The median rwTTNT following sequence was numerically longer among the R-T cohort compared to the T-R cohort (9.3 [8.4, 10.3] vs. 8.6 [7.8,9.4] months). Index treatment was not significantly associated with rwOS (HR=1.2, p=0.2), rwPFS (HR=0.9, p=0.4), or rwTTNT (HR=1.1, p=0.6) Conclusion: Treatment sequence numerically favored R-T and provided an additional survival benefit of 2.6 months in this cohort, although this was not statistically significant. Providing access to the regorafenib and FTD/TPI +/- bevacizumab are critical to maximizing patient benefit and optimizing patient care in advance stages of mCRC.