KRAS mutation and primary tumor location do not affect efficacy of bevacizumab-containing chemotherapy in stagae IV colorectal cancer patients

Sun, David; Shi, Yan; Wang, Yanrong; Lv, Yao; Yan, Huan; Mao, Hui; Wang, Zhi-kuan; Wu, Zhi‐Yong; Shi, Weiwei; Dai, Guanghai

doi:10.1038/s41598-017-14669-2

Cited by 15 publications

(8 citation statements)

References 33 publications

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“…A posthoc analysis of this trial suggested a benefit from bevacizumab in addition to chemotherapy independently of primary tumor localization regarding the reported endpoint progression-free survival (28). Similar results were reported in a prospective trial on a Chinese cohort (29).…”

Section: Discussionsupporting

confidence: 81%

Impact of Primary Tumor Localization on the Efficacy of Bevacizumab in Metastatic Colorectal Cancer

et al. 2018

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Section: Discussionsupporting

confidence: 81%

Impact of Primary Tumor Localization on the Efficacy of Bevacizumab in Metastatic Colorectal Cancer

et al. 2018

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“…To the best of our knowledge, the influence of ECOG score on the prognosis of patients was confirmed in a previous study, which suggested that the higher the score, the worse the prognosis. 26 Results of the Cox regression analysis in our study indicated that patients with ECOG 1-2 scores were associated with worse DFS. On the other hand, in view of the poor adherence to drug administration among patients with NSCLC in the real world, the median course of adjuvant chemotherapy in our study was three (range one to five), and the insufficient adjuvant chemotherapy failed to reduce the recurrence risk of patients with NSCLC, in accordance with proved a previous study.…”

Section: Discussionmentioning

confidence: 47%

<p>Influence of Programmed Death Ligand-1-Gene Polymorphism rs822336 on the Prognosis and Safety of Postoperative Patients with NSCLC Who Received Platinum-Based Adjuvant Chemotherapy</p>

Zhao¹,

Zhang²,

Chen

et al. 2020

CMAR

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This study was done to investigate the influence of PDL1-gene polymorphism on the prognosis and safety of postoperative patients with non-small cell lung cancer (NSCLC) who had received platinum-based adjuvant chemotherapy. Methods: A total of 289 postoperative patients with NSCLC who had received platinumbased adjuvant chemotherapy from January 2012 to June 2019 participated in this study. Recurrence status and adverse reactions were documented during adjuvant chemotherapy. Overall survival (OS) data were obtained through telephone follow-up. DNA extracted from hematologic specimens was genotyped for PDL1-gene polymorphism. Associations between genotype status and prognosis were assessed using Kaplan-Meier survival analysis, and multivariate adjustment was performed using Cox regression analysis. Results: Median disease-free survival of the 289 patients with NSCLC was 3.3 years and median OS 4.9 years. With regard to the PDL1 gene polymorphism, only rs822336 was of clinical significance in the subsequent analysis. The minor-allele frequency of rs822336 was 0.21, and distribution of the three genotypes was in accordance with the Hardy-Weinberg equilibrium (P=0.807). Survival analysis according to genotype status suggested that median disease-free survival of patients with GG and GC/CC genotypes was 2.8 and 4.1 years, respectively (P=0.01). Median OS of patients with GG and GC/CC genotypes was 4.1 and 5.4 years, respectively (P=0.008). However, the safety analysis failed to find a significant association between the polymorphism and adverse reactions. Interestingly, expression analysis of RNA extracted from peripheral blood mononuclear cells indicated that PDL1-mRNA expression of patients with the GG genotype was significantly higher than for the GC/CC genotype (P<0.001). Conclusion: The prognosis of postoperative patients with NSCLC who have received platinum-based adjuvant chemotherapy may be influenced by the rs822336 polymorphism through mediation of the mRNA expression of PDL1.

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“…Due to this association, CDKN2A alterations were not considered as a new independent marker for bevacizumab treatment outcome. Results from the literature do not show survival differences in bevacizumab-treated CRC patients according to KRAS mutation status [10,11,17]. Similarly, TP53 mutation status was not associated with survival in bevacizumab-treated patients [11].…”

Section: Discussionmentioning

confidence: 99%

TP53 DNA Binding Domain Mutations Predict Progression-Free Survival of Bevacizumab Therapy in Metastatic Colorectal Cancer

Hsu

You

Chen³

et al. 2019

Cancers

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(1) Background: Bevacizumab-based regimens are a standard treatment for metastatic colorectal cancer (mCRC) patients, however meaningful clinical biomarkers for treatment benefit remain scarce. (2) Methods: Tumor samples from 36 mCRC patients treated with bevacizumab-based chemotherapy underwent comprehensive genomic profiling. Alterations in frequently altered genes and important signaling pathways were correlated with progression-free survival (PFS). (3) Results: Overall genetic alteration analysis of investigated genes and pathways did not identify promising new predictors of PFS. However, when considering mutation subtypes, TP53 DNA binding domain (DBD) missense mutations were associated with prolonged PFS (HR, 0.41; 95% CI, 0.13−0.65; p = 0.005). In contrast, TP53 truncating mutations were associated with short PFS (HR, 2.95; 95% CI, 1.45−27.50; p = 0.017). Importantly, neither TP53 mutation subtype was associated with overall response rate. In multivariate analysis, TP53 DBD missense mutations remained an independent PFS predictor (HR, 0.31; 95% CI, 0.13–0.77; p = 0.011). The other genetic factor independently associated with PFS were PTPRT/PTPRD deleterious alterations, which we previously identified in a screen for biomarkers of bevacizumab response. (4) Conclusions: TP53 DBD missense mutations may predict prolonged PFS in mCRC patients treated with bevacizumab-based therapy. Analyses of TP53 mutations as clinical biomarkers should take the biological impact of different mutation subtypes into consideration to improve patient stratification.

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KRAS mutation and primary tumor location do not affect efficacy of bevacizumab-containing chemotherapy in stagae IV colorectal cancer patients

Cited by 15 publications

References 33 publications

Impact of Primary Tumor Localization on the Efficacy of Bevacizumab in Metastatic Colorectal Cancer

Impact of Primary Tumor Localization on the Efficacy of Bevacizumab in Metastatic Colorectal Cancer

<p>Influence of Programmed Death Ligand-1-Gene Polymorphism rs822336 on the Prognosis and Safety of Postoperative Patients with NSCLC Who Received Platinum-Based Adjuvant Chemotherapy</p>

TP53 DNA Binding Domain Mutations Predict Progression-Free Survival of Bevacizumab Therapy in Metastatic Colorectal Cancer

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