1. Published online September 20, 2017 by JAMA Surgery
Association of Primary Tumor Site with Mortality in Patients Receiving Bevacizumab and Cetuximab for Metastatic Colorectal Cancer
Mayada Aljehani, DrPH
Published online September 20, 2017 by JAMA Surgery

2. Introduction/ Background
4/8/2019
OUTLINE
Conclusions
Limitations
Discussion
Results
Methods
Introduction/ Background

3. 4/8/2019
BACKGROUND
Colorectal Cancer (CRC) is the 2nd leading cause of cancer deaths in U.S.
About 20% of CRCs are stage IV at diagnosis (mCRC), predicting poor survival
Treatment of mCRC includes systemic chemotherapy (SC) that recently is sometimes accompanied by targeted biologic therapy
Biologic therapies anti-VEGF monoclonal antibodies such as bevacizumab and anti-EGFR monoclonal antibodies such as cetuximab are increasingly used to treat metastatic colorectal cancer (mCRC)
Recent investigations have shown that primary tumor location as right or left impacts response to biologic therapy and survival in metastatic colorectal cancer
Current NCCN recommendations do not differentiate between right and left mCRC
Sources: Tejpar, et al. JAMA Oncol. 2017;3(2):

4. TARGETED BIOLOGIC THERAPY FOR mCRC
The two most frequently used targeted biologic therapies for mCRC are two monoclonal antibodies
Bevacizumab
Vascular endothelial growth factor (VEGF) inhibitor
Cetuximab
Epidermal growth factor (EGFR) inhibitor

5. ANATOMIC SUBSITE (Location)
Right colon
Left colon
~45%
~55%

6. 4/8/2019
BACKGROUND
Recent clinical trial showed better survival for left-sided mCRC treated with SC + biologic therapy, relative to right-sided malignancies
These findings have been challenged because of the highly select characteristics of patients in clinical trials that limit generalizability of findings
Biologic therapies anti-VEGF monoclonal antibodies such as bevacizumab and anti-EGFR monoclonal antibodies such as cetuximab are increasingly used to treat metastatic colorectal cancer (mCRC)
Recent investigations have shown that primary tumor location as right or left impacts response to biologic therapy and survival in metastatic colorectal cancer
Current NCCN recommendations do not differentiate between right and left mCRC
Sources: Tejpar, et al. JAMA Oncol. 2017;3(2):

7. 4/8/2019
BACKGROUND
Survival benefits from biologic therapy for mCRC influenced by tumor location (right vs. left) remains uncertain
Current National Comprehensive Cancer Network (NCCN) treatment recommendations for mCRC are incomplete
Biologic therapies anti-VEGF monoclonal antibodies such as bevacizumab and anti-EGFR monoclonal antibodies such as cetuximab are increasingly used to treat metastatic colorectal cancer (mCRC)
Recent investigations have shown that primary tumor location as right or left impacts response to biologic therapy and survival in metastatic colorectal cancer
Current NCCN recommendations do not differentiate between right and left mCRC

8. 4/8/2019
OBJECTIVE
To evaluate the impact of primary tumor location on mortality in a diverse population-based dataset among patients with mCRC receiving systemic chemotherapy and bevacizumab or cetuximab
Our objective was to evaluate the impact of primary tumor location on mortality in a diverse population-based dataset among patients with metastatic colorectal cancer receiving systemic chemotherapy and either bevacizumab or cetuximab

9. 4/8/2019
METHODS
Retrospective review of statewide California Cancer Registry data
Between
Stage IV colorectal adenocarcinoma
Patients ages that received systemic chemotherapy (SC) alone or SC and bevacizumab or cetuximab
Single primary tumor classifiable as right (appendix to transverse colon) or left (splenic flexure to rectum)
We performed a retrospective review of statewide California cancer registry data between among patients with Stage IV colorectal adenocarcinoma.
We included patients ages that received systemic chemotherapy alone or systemic chemotherapy and either cetuximab or bevacizumab who also had a single primary tumor classifiable as right (defined as appendix to transverse colon) or left (defined as splenic flexure to rectum)
Bevacizumab and cetuximab were selected as they are the most common monoclonal antibodies used in treatment for metastatic colorectal cancer.

10. OUTCOMES & COVARIATES
Overall Survival: Time from date of diagnosis to death or to last date of study follow-up (December 31, 2014)
Covariates: Adjusted for age, year of diagnosis, and SES as well as signet ring and mucinous histologies

11. STATISTICAL ANALYSES Univariable: Counts & percentages χ2 tests
Median follow-up & survival:
Kaplan-Meier
Log-rank tests
Multivariable:
Propensity score weighting
Cox regression
Purposeful variable selection

12. STATISTICAL ANALYSES Subgroup Analyses:
KRAS status wild-type patients diagnosed
Proportionality Assumption:
Log-log plot
Schoenfield’s residual correlation
Significance level:
Two sided α=0.05 (95%CI)

15. 4/8/2019

18. DISCUSSION
Survival differences for mCRC by location and biologic therapy type, like previous clinical trials, validating our findings and adding generalizability
The importance of considering tumor location in decisions about mCRC treatment
Right-sided mCRC is associated with poorer survival regardless of the biologic therapy type

19. LIMITATIONS Lack of genetic data (including MSI, BRAF, NRAS)
Absence of information on tumor recurrence
Unknown metastatic target tissues that define different survivals
Does not utilize distinctions in types of chemotherapy used

20. CONCLUSIONS
KRAS wild-type right-sided mCRC treated with cetuximab had poorer survival
KRAS wild-type left-sided mCRC had better survival with cetuximab
Further investigations are needed to understand the biologic differences that impact outcomes between right and left colon cancer

21. THANK YOU!