Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture

BACKGROUND Angiogenesis inhibitors(AIs)combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer(CRC).Aflibercept(AFL)is an option for second-line treatment of CRC,according to the‘VELOUR’trial.Currently,we can choose from three AIs,including bevacizumab,ramucirumab,and AFL.Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action.We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.AIM To determine and compare the efficacy and safety profiles of AFL in the secondline and salvage therapy settings.METHODS Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan(FOLFIRI)regimen were collected retrospectively from six institutions in Japan,for the period from May 2017 to March 2019.Patient characteristics collected included age,sex,tumor location,RAS and RAF status,metastatic sites,number of previous treatment cycles,therapeutic response,adverse events,duration of previous AI treatment,and survival time.The end points were time to AFL treatment failure(aTTF)and median survival time post-AFL(aMST).Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting,which was defined as the days since the end of secondline therapy.RESULTS All 41 patients who received AFL+FOLFIRI for advanced CRC had metastatic or unresectable cancer.Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting.The patient characteristics were similar in the two groups,except for two factors.The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients(144 d vs 323 d,P=0.006).In the second-line and salvage therapy groups,the objective response rates were 11%and 0%,respectively(P=0.50),and the disease control rates were 53%and 50%,respectively(P=1.00).In the second-line and salvage therapy groups,the aTTF(123 d vs 71 d,respectively),aMST(673 d vs 396 d,respectively),and incidence of adverse events of grade 3[8(36%)vs 9(47%)]were not significantly different between the two groups.CONCLUSION AFL can be used to treat advanced CRC patients,with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

Recent trends in bone metastasis treatments:A historical comparison using the new Katagiri score system

BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.