Real-World Data Identify Factors Associated With Long-Term Response to Regorafenib in mCRC

Richard D. Kim, MD

Favorable ECOG performance status, lower lactate dehydrogenase levels, and absence of BRAF and KRAS mutations at baseline were among some of the characteristics associated with long-term response to regorafenib (Stivarga) in patients with metastatic colorectal cancer (mCRC), according to real-world data that were presented at the 2024 Gastrointestinal Cancers Symposium.

“This real-world study, performed in the USA and outside of a controlled clinical trial setting, aimed to determine the proportion of patients who had a long-term response to regorafenib,” the authors said in their poster presentation.

The study analyzed data from 2326 patients who started regorafenib monotherapy between July 1, 2013, and December 31, 2022. A total of 346 patients (15%; median age, 65 years) had a long-term remission of 5 or more months, with 503 patients (22%; median age 65 years) having a long-term remission of 4 months or longer.

Among the cohort of patients with a remission lasting 5 months or longer, less than half (46%; n=160) had stage IV disease at the time of diagnosis. The majority (68%; n=237) had an ECOG performance status of 0-1, and/or received prior bevacizumab (64%; n=221). Of patients who were tested at index, the median carcinoembryonic antigen (CEA) level was 35 ng/mL (range, 9-139). Slightly more than half (51%) had a KRAS mutation, and 5% had a BRAF mutation at index.

The median time from CRC diagnosis to index date was 39.2 months (range, 25.1-64.1), and 33% and 23% received regorafenib as a third-line or fourth-line treatment, respectively. Median time to regorafenib discontinuation was 7.3 months (95% CI, 6.9-7.8).

Findings showed that patient characteristics were similar among patients who had remissions lasting 4 months or longer, with 48% (n=241) having stage IV at diagnosis, 66% (n=332) having an ECOG performance status of 0-1; 68% (n=341) having prior bevacizumab; median CEA level of 40 (range, 9-152); 54% and 6% harboring KRAS and BRAF mutations, respectively.

Median time from diagnosis to index was 38.6 months (range, 24.8-62.8), with 34% and 23%, respectively, receiving regorafenib as a third-line or fourth-line therapy. The median time to treatment discontinuation was 6.0 months (95% CI, 5.-6.2).

Among patients who started regorafenib therapy before the year 2019, (n=1,070), 14% had a remission lasting 5 or more months, while 21% had a remission lasting 4 months or longer. In patients who started the therapy 2019 or later, (n=1,256), 16% and 22% had remissions lasting 5 months and 4 months or longer, respectively.

“These results increase our understanding of patient profiles and factors that influence the effectiveness of regorafenib in real-world clinical practice,” the poster read.

Reference

Kim RD, Pan X, Ostojic H, et. al. Real-world (RW) study in patients (pts) with metastatic colorectal cancer (mCRC) with long-term responses to regorafenib in the USA. J Clin Oncol. 2024;42(suppl 3)48. doi.10.1200/JCO.2024.42.3_suppl.48