1035 - Real world experience with Regorafenib in dose escalation schedule in metastatic colorectal cancer in Indian patients

Background

Regorafenib is a multikinase inhibitor approved for treatment in metastatic colorectal cancers (mCRC) in the 3^rd line setting. Though phase 3 data has revealed improvement in overall survival (OS), this has not been used extensively in our patients. This is due to toxicity and inability of our patients to tolerate the full dose of 160mg/day. The aim was to nalyse the efficacy and toxicity of Regorafenib in Indian patients in a dose escalation schedule.

Methods

Pateints of mCRC treated with Regorafenib between Jan 2015 to Jan 2018 at our hospital were nalysed. They had progressed on 2 lines of chemotherapy and many also received biological therapies (Cetuximab in Ras and B Raf wild type and Bevacizumab). The starting dose was 80mg/day in 3 weeks on and 1 week off schedule in most patients, with escalation to 120mg/day after 2 weeks and to 160mg/day in the 2^nd cycle, if well tolerated. The endpoints were progression free survival (PFS) and adverse events (Aes).

Results

33 patients received Regorafenib between Jan 2015 to Jan 2018. 16 patients had Ras wild type, 13 had Ras mutations and 4 had B Raf mutations. 10 wild type patients (62.5% of wild type patients) received Cetuximab previously and 22 patients (66.6%) received Bevacizumab. The median PFS with Regorafenib was 4 months (range 1 to 21 months). There were 5 patients who were on treatment for 12 months, and 1 patient continued on treatment for 21 months with partial response. Hand foot skin reactions (HFSR) was the most common toxicity and was seen in 20 patients (60%) at 80mg/day. HFSR was seen in 80% patients when the dose was escalated to 120mg/day. No patient could continue on 160mg/day. Other side effects were fatigue in 12 patients (36.3%), diarrhea in 6 patients (18%), hypertension in 5 patients (15%) and altered LFTs in 3 patients.

Conclusions

Regorafenib at a starting dose of 80mg was well tolerated. Increasing dose to 120mg/day increased the side effects especially the HFSR, and none of our patients could tolerate 160mg/ day. The median PFS was 4 months; but few of our patients had a very long benefit with Regorafenib, with 5 patients crossing 1 year. The optimum tolerated dose in our patients is 80mg – 120mg/day. Better experience in managing the toxicities would add longer benefit in our patients.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Amit Rauthan.

Funding

Has not received any funding.

Disclosure

A. Rauthan: Advisory board: Roche, Merck, Bayer, Pfizer. All other authors have declared no conflicts of interest.