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Bevacizumab in metastatic colorectal carcinoma: A retrospective review of real-world efficacy
Background
We present to you a retrospective review of our institutional use of Bevacizumab in colorectal cancer with respect to chemotherapeutic regimen, efficacy and morbidity relating to its use over a 5-year period in the Maltese islands. We also evaluated whether these outcomes were influenced by patient demographics or tumor characteristics including molecular markers e.g., RAS and BRAF where available.
Methods
Patients with a diagnosis of metastatic colorectal cancer were identified through our cancer registry and chemotherapy prescribing databases. Patient demographics and tumor characteristics (grade, stage, tumor sidedness) including molecular profiling (K-RAS, BRAF V600E, MSI) were collected. Treatment modality including chemotherapeutic combination and previous lines of therapy as well as radiotherapy, surgery or intervention ablation techniques were documented. Morbidity including hospital admissions during bevacizumab therapy including severity of treatment was documented. Our standard of reference for this audit was the ESMO clinical practice guidelines for the management of metastatic colorectal carcinoma (mCRC). The primary endpoint studied was progression free survival (PFS). Individual variables collected were analyzed for their significance using Cox Regression Analysis via SPSS based software.
Results
54 patients were included in our study over a 5-year period (2015-2020). Folfox was preferred as a first line chemotherapy regimen whilst Folfiri was favored as a second line option. Bevacizumab was used in the first line setting in 29% of the patients and 2nd line agent in in 36% of the patients. 14 patients still received bevacizumab despite showing disease progression with mPFS 48.5 weeks while 38 patients discontinued bevacizumab despite progression with an mPFS of 27.5 weeks. 24 patients had a KRAS mutant tumor whilst 18 patients were KRAS wild type. The mPFS for KRAS mutant tumor was 27 weeks when treated with bevacizumab in combination with Folfox (n=8, mPFS=39 weeks) or Folfiri (n=10, mPFS 26 weeks). For those patients with a K-RAS wild type tumor, the mPFS was 35 weeks (Folfox-Bev n=2, mPFS=69 weeks; Folfiri-Bev n=8, mPFS= 43 weeks). The only variables achieving statistical significance were the contribution of age and use of fluoropyrimidine based cytotoxic therapy. The first parameter noted that an age cut off below or equal to 60 years of age in contrast to patients above 60 years of age had variable outcomes. The second criterion related to the use of fluoropyrimidines in combination with bevacizumab in contrast to those patients treated with a non-fluoropyrimidine regimen such as single agent irinotecan or lonsurf. Only 7% of patients experienced severe toxicity needing hospitalization.
Conclusions
In our research, we confirm that it is the addition of a fluoropyrimidine-containing regimen to bevacizumab that is statistically significant, especially in the patient cohort under the age of 60 years. This is in line with current data that confirms that bevacizumab in combination with any fluoropyrimidine-based chemotherapy is more effective than any fluoropyrimidine-based chemotherapy alone. We also presume that the younger patient is likely to have better performance status, less co-morbidities and improved tolerability to chemotherapy, possibly explaining the improved outcomes in PFS.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
