Regorafenib and Trifluridine/Tipiracil: Hospitalization and Clinical Outcomes in the Treatment of Metastatic Colorectal Cancer

Analysis of Hospitalization Probability

In cases of mCRC progression after the 1st and 2nd lines of treatment, the European Society for Medical Oncology (ESMO) recommends either the tyrosine kinase inhibitor regorafenib or the cytotoxic combination of trifluridine/tipiracil. The different mechanisms of action of regorafenib and trifluridine/tipiracil are also associated with different toxicity profiles. Regorafenib use often results in fatigue and skin reactions such as palmar-plantar erythrodysesthesia, whereas the main adverse effect (AE) of trifluridine/tipiracil is hematotoxicity (mainly neutropenia).

The differing safety profiles of the two agents have led to some misperceptions regarding their actual tolerability and treatment complications within the oncology community. Therefore, a study by Austrian oncologists aimed to compare the tolerability of regorafenib and trifluridine/tipiracil, with the assessed parameter being the need for hospitalization during treatment.

Data Analysis and Results

This retrospective study analyzed data from 93 consecutive patients who initiated either regorafenib or trifluridine/tipiracil therapy as a 3rd line of treatment for mCRC between January 2013 and May 2019. Sixty-nine individuals were treated with regorafenib as the 3rd line, while twenty-four received trifluridine/tipiracil. Thirty-eight patients subsequently underwent a 4th line of treatment, with seven treated with regorafenib and thirty-one with trifluridine/tipiracil. The median duration of therapy was 64 days for regorafenib and 82 days for trifluridine/tipiracil. The median OS from the start of the 3rd line treatment was 10.4 months.

During therapy, there were 77 hospitalizations. In the 3rd line, 48% of patients treated with regorafenib and 42% of those on trifluridine/tipiracil were hospitalized one or more times. In the 4th line treatment, it was 57% vs. 29%. Multivariate analysis showed that the use of regorafenib was significantly associated with an increased risk of hospitalization (hazard ratio [HR] 1.95; 95% confidence interval [CI] 1.07–3.54) compared to trifluridine/tipiracil. The corresponding probability of hospitalization was 30% at 5 weeks in the regorafenib arm versus 18% in the trifluridine/tipiracil arm, and 41% vs. 28% at 10 weeks. The average length of hospital stay did not differ significantly between the two groups.

Gastrointestinal AEs were the reason for hospitalization only in patients treated with regorafenib (15% of patients). Hospitalizations due to infections, conditions related to the primary disease, or other AEs occurred comparably often in both groups. Treatment had to be interrupted in 30% of hospitalized patients in the regorafenib arm and 26% in the trifluridine/tipiracil arm.

Hospitalization did not significantly affect OS in patients, whether those undergoing only 3rd line treatment (n = 55; median OS 5.7 months in non-hospitalized patients [95% CI 3.9–10.5] vs. 5.4 months in hospitalized patients [95% CI 2.8–9.6]) or those treated with both 3rd and 4th line treatments (n = 38; median OS 12.2 months in non-hospitalized patients [95% CI 10.6–28.8] vs. 18.6 months in hospitalized patients [95% CI 6.3 to not reached]).

Conclusion

Based on experience from Austrian clinical practice, regorafenib is associated with a higher likelihood of hospitalization compared to trifluridine/tipiracil. Regardless of the cause, hospital stays likely do not impact patient survival. Given the significant gastrointestinal toxicity during regorafenib treatment, increasing awareness about the specific safety profiles of both drugs would be beneficial. Early detection of adverse effects and prompt intervention can prevent many complications and hospital stays.

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Source: Huemer F., Piringer G., Schlintl V. et al. Hospitalizations and clinical outcome in metastatic colorectal cancer during regorafenib or TAS-102 therapy. Cancers 2020; 12 (10): 2812, doi: 10.3390/cancers12102812.