Chemoembolization in Conjunction with Bevacizumab: Preliminary Results
“The whole is greater than the sum of its parts” – SYNERGY! This is a concept that has been utilized a lot in oncology and modern medicine. Interventional oncology is no exception especially as new cancer treatment options continue to emerge. What we have lacked however, is the robust evidence to support this concept in our blossoming interventional oncology sphere.
In a recently published proof of concept paper, researchers from Italy and Slovenia published their preliminary results for chemoembolization in combination with Bevacizumab in colorectal liver metastasis (CR-LM). In this prospective observational single center trial, 6 patients with unresectable CR-LM that were naïve to standard chemotherapy and had good performance status (ECOG 0 and 1).
The patients received two cycles of DEB-IRI chemoembolization using the PEG embolic delivery platform loaded with 100 mg irinotecan. Bevacizumab was initiated 15 days after the first chemoembolization and then biweekly for a total of 8 cycles. OS, PFS, TTP, mRECIST tumor response, adverse effects and QoL were measured.
At 3 months: 2 pts (33%) CR, 2 pts (33 %) PR, 1 pt (17%) SD and 1 patient progressed (patient had advanced disease and on 4th line chemotherapy). Median overall survival (OS) was 10 months (range 7–15 months), median time to progression was 3 months (range 2–5 months), and median progression-free survival was 7 months (range 3–15 months). There was a reported increase in quality of life in 4 patients (66%)
There were no complications during chemoembolization but mild to moderate adverse events related to post chemoembolization syndrome were reported. Bevacizumab related adverse effects were hypertension (17%) and skins rash (33%).
Figure 1. Tumor response at 1, 3, and 6 months after first transarterial chemoembolization. CR = complete response; PD = progressive disease; PR = partial response; SD = stable disease.
Exploiting increased expression of VEGF post chemoembolization to create synergistic localized oncologic benefits was demonstrated with (Hepatocellular carcinoma) HCC where locoregional chemoembolization has had a very significant role over the last 3 decades. We have limited clinical data that this concept is also clinically beneficial to patients with CRC-LM.
Hepatocellular carcinoma tends to be hypervascular and largely depends on the hepatic arterial tree vs CRC - LM which are generally hypovascular and largely depend on portal venous circulation. The impact of these potential perfusion differences on the concept and ability to translate to meaningful clinical benefit or difference is still not known. This paper provides a platform and basis for us to continue to investigate this potentially beneficial option to patients and exciting frontier for interventional oncology.
The median OS of 10 months in this very small cohort is lower than previously published median OS of 14 months with DEB-IRI alone. It is important to note the study recruited technically the “worst” responders with >3 failed lines of systemic chemotherapy and attenuated expected OS. The 3 months mRECIST tumor control rates appeared comparable with previous trials of all comers. Therefore, the preliminary results suggest a very interesting trend which is potentially beneficial to patients with advanced CRC-LM.
This sets an excellent foundation for expanding this to larger multicenter cohorts to validate this concept in chemo naïve CRC-LM and also to perhaps consider trials that extend this concept to early treatment lines for CRM-LM.
The study has multiple weaknesses, not least: sample size, single center, lack of control group, no randomization to name a few. The authors do a good job to acknowledge these and many more.
Click here for the abstract
Fiorentini G, Sarti D, Aliberti C, Carandina R, Mulazzani L, Felicioli A, Guadagni S. Chemoembolization in Conjunction with Bevacizumab: Preliminary Results. J Vasc Interv Radiol. 2018 Sep;29(9):1236-1239. doi: 10.1016/j.jvir.2018.04.022. PubMed PMID: 30146190.
Rodrick C Zvavanjanja MD, MSc, FRCR, DABR(VIR/DR)
Department of Diagnostic and Interventional Radiology
University of Texas at Houston McGovern Medical School