Considering data from the real-world setting is becoming increasingly important with the use of anticancer agents, as there is likely a big difference between patients in a clinical trial and patients in the real world, said Juan Manuel O’Connor, MD. During the 2018 ESMO Congress, O'Connor presented real-world dosing findings for regorafenib in patients with metastatic colorectal cancer.
Considering data from the real-world setting is becoming increasingly important with the use of anticancer agents, as there is likely a big difference between patients in a clinical trial and patients in the real world, said Juan Manuel O’Connor, MD. During the 2018 ESMO Congress, O'Connor presented real-world dosing findings for regorafenib (Stivarga) in patients with metastatic colorectal cancer (mCRC).1
Regorafenib is currently indicated for the treatment of refractory patients with mCRC at a dose of 160 mg daily for a 3-week-on/1-week-off schedule. In final results from the prospective, observational CORRELATE study, real-world data with regorafenib in patients across 13 countries in Europe, Latin America, and Asia were gathered and reported on. The principal aim of this study was to assess safety.
Of the 1037 patients evaluated, 57% started treatment at 160 mg, 30% began at 120 mg, and 13% began at ≤80 mg. Investigators noted that dose reductions were most frequent in the 160-mg group, and treatment modifications were due mostly to treatment-emergent adverse events (TEAEs; 66%).
Grade ≥3 TEAEs occurred in 62% of patients, 36% of which were attributed to regorafenib. The most common of the grade ≥3 TEAEs related to regorafenib were fatigue (9%), hand-foot skin reaction (7%), and hypertension (6%). Although grade 5 TEAEs were observed in 17% of patients, only 1% were deemed to be regorafenib related.
The safety profile of regorafenib has led to studies evaluating dose escalation as a way to limit TEAEs. Most recently, the NCCN revised its guidelines regarding regorafenib, based on findings from the ReDOS study.2
In ReDOS, investigators evaluated a dose-escalation strategy of regorafenib beginning at 80 mg and ending at 160 mg for previously treated patients with mCRC. Positive overall survival (OS) and progression-free survival (PFS) data led to the recommendation of a starting dose of 80 mg/daily on days 1 to 7, escalating to 120 mg/daily on days 8 to 14, and concluding with 160 mg/daily on days 15 to 21. From there, subsequent cycles should use 160 mg of regorafenib on days 1 to 21 every 28 days, according to the NCCN.
In an interview withTargeted Oncologyduring the 2018 ESMO Congress, O'Connor, head, Department Gastrointestinal Oncology, Department of Clinical Oncology, Institute Alexander Fleming, Buenos Aires, discussed the final results of the CORRELATE regorafenib study in patients with mCRC, emphasizing the importance of real-world data.
TARGETED ONCOLOGY:Could you please share the final results from CORRELATE?
O’Connor:The approval dose of regorafenib for the treatment of patients with mCRC is 160 mg. There are some differences between the real-world setting and the patients included in the randomized clinical trial. The aim of our study was to look at the data from the real-world setting of refractory mCRC in more detail.
The final results of our study described a starting dose in patients based on the decisions of the treating physicians. Of the patients enrolled on the study, 57% of those who started at the recommended dose of 160 mg, 30% at 120 mg, and 13% at 80 mg. That is very important information.
TARGETED ONCOLOGY:What are your thoughts on regorafenib in a dose-escalation regimen?
O’Connor:There were very important data from the ReDOS trial based on the escalation and re-escalation. In our study, around 20% of our patients required an escalated dose. We plan to analyze this subgroup based on the new data coming from the ReDOS trial.
The primary objective of our study was to characterize the use of regorafenib in a real-world setting based on safety and efficacy, mainly in terms of progression-free and overall survival. Based on the observational study, safety is a very important issue to keep in mind.
TARGETED ONCOLOGY:Can you speak to the tolerability of regorafenib?
O’Connor:One of the problems with the use of regorafenib is the starting dose. Therefore, in the real-world observational study, the data were not equal in terms of safety. There are many doctors that used a starting dose that was different than the recommended dose. It is important to keep the ReDOS data in mind with this study. These are important data because we have more data from the treating physician perspective, as they feel more confident in the dosing when treating patients with refractory mCRC.
TARGETED ONCOLOGY:What would be your take-home message about CORRELATE?
O’Connor:Our take-home message from this observational study was that, despite the flexible doses of regorafenib, there was no impact in the effectiveness in terms of the median OS and median PFS. It was 7.7 months in terms of median OS, which was a little bit more than the 2 previous trialsCORRECT and CONCUR. The median PFS was 2.9 months.
In the future, it is important to consider data from the real-world setting. There is likely a big difference between the patients included in the randomized clinical trial compared with the real world. We will get more information from routine clinical practice, mainly in terms of safety.