scholarly journals Association of RAS mutations with early progression after first-line systemic therapy in patients with initially unresectable colorectal cancer liver metastasis

2021 ◽  
Author(s):  
Di Cao ◽  
Cong Li ◽  
Chi Zhou ◽  
Weili Zhang ◽  
Zhenhai Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factor ◽  
Disease Progression ◽  
Systemic Therapy ◽  
Driver Gene ◽  
First Line ◽  
Early Disease ◽  
Ras Mutation ◽  
Ras Mutations ◽  
Early Progression

Abstract Purpose Patients with initially unresectable colorectal cancer with liver metastases (IU-CRLM) need to undergo first-line systemic therapy with the aid of chemotherapy. However, the driver gene attributed to early progression in IU-CRLM patients after first-line systemic therapy remains unclear. Our study explored the RAS mutation status related to early progression in IU-CRLM patients. Methods A total of 193 IU-CRLM patients with RAS status detection were retrospectively enrolled from December 2012 to January 2020. We defined early progression as tumour progression within 6 months after first-line systemic therapy. Univariate and multivariate logistic regression for early progression were implemented to identify the risk factors. Results RAS mutations were found in 51 (26.0%) IU-CRLM patients. A total of 107 (55.4%) patients were confirmed to have early progression after first-line systemic therapy. RAS mutation was significantly related to early disease progression (66.7% vs. 49.3%, P=0.033). Logistic analysis results showed that RAS mutation (OR=2.962, 95% CI 1.354-6.478, P=0.007) was an independent risk factor for early disease progression. Conclusions Mutated RAS was an important risk factor for early progression in IU-CRLM patients after first-line systemic therapy.

scholarly journals Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shun Yamamoto ◽  
Kengo Nagashima ◽  
Takeshi Kawakami ◽  
Seiichiro Mitani ◽  
Masato Komoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Early Disease ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

Abstract Background The ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab. Methods The subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis. Results Sixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0–1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46–1.34], p = 0.373, adjusted HR: 0.87 [0.41–1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38–1.12], p = 0.125, adjusted HR 0.53 [0.27–1.07], p = 0.078). Conclusion In mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.

scholarly journals Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression

Haematologica ◽  
2020 ◽  
Vol 105 (5) ◽  
pp. 1465-1465
Author(s):  
John F. Seymour ◽  
Robert Marcus ◽  
Andrew Davies ◽  
Eve Gallop-Evans ◽  
Andrew Grigg ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Disease Progression ◽  
Poor Survival ◽  
Early Disease ◽  
Early Progression

Prognostic and predictive impact of EGFR and K-ras mutation, and EGFR gene copy number in patients with advanced non-small cell lung cancer (NSCLC) who received first-line cytotoxic chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8096-8096
Author(s):  
Y. Tambo ◽  
K. Kasahara ◽  
T. Sone ◽  
H. Kimura ◽  
A. Sakai ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Predictive Marker ◽  
Cytotoxic Chemotherapy ◽  
Egfr Mutations ◽  
Gene Copy ◽  
First Line ◽  
Ras Mutation ◽  
Egfr Amplification ◽  
Ras Mutations ◽  
Egfr Tki

8096 Background: Epidermal growth factor receptor (EGFR) mutations, amplification, and K-ras mutations are known as predictive factor of the EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients (pts) with NSCLC. Prognostic influences of those biomarkers remain the matter to be discussed. Methods: Consecutive pts with advanced NSCLC who were examined EGFR genotype and received 1st line cytotoxic chemotherapy were enrolled. EGFR amplification and K-ras mutation were analyzed if sufficient tumor samples were available. Results: 87 pts were enrolled in this study. EGFR mutations or K-ras mutations were found in 26 of 87 (29.9%) or 2 of 65 (3.1%) pts, respectively. As to objective response rate (ORR), no significant differences were observed among pts with EGFR mutations, K-ras mutations, and pts without both mutations. Progression free survival (PFS) in 1st line cytotoxic chemotherapy was 8.4, 1.0, and 3.9 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. PFS was longer in pts with EGFR mutations compared with the pts without both mutations (p=0.0234). We also found the pts with K-ras mutations had shorter PFS compared with pts without both mutations (p=0.0203). Overall survival (OS) was 29.7, 2.3 and 13.4 months in pts with EGFR mutations, with K-ras mutations, and pts without both mutations, respectively. Significant differences were found between pts with EGFR mutation and without both mutations (p=0.0001) and between pts without both mutations and with K-ras mutations (p=0.0001). Pts with EGFR amplification were found in 21 of 78 (26.9%). There were no differences between EGFR amplification positive and negative in terms of ORR, PFS and OS. 87 of 68 (78.2%) pts received EGFR-TKI therapy in the second line or later. As previously reported, both EGFR mutations and amplifications were good predictive marker of ORR, PFS and OS in pts treated with EGFR-TKI. Conclusions: EGFR mutations were good predictive marker and K-ras mutations were poor predictive marker in first line cytotoxic chemotherapy. There is the possibility that EGFR and K-ras mutations have the prognostic impact in advanced NSCLC. [Table: see text]

Using low sensitivity of direct sequencing to detect K-ras mutations? A new method for improving diagnostic accuracy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22100-e22100
Author(s):  
Chi-Kuan Chen
Keyword(s):  
Colorectal Cancer ◽  
Real Time ◽  
Cancer Patients ◽  
Real Time Pcr ◽  
Mutation Detection ◽  
Direct Sequencing ◽  
Standard Procedure ◽  
Ras Gene ◽  
Ras Mutation ◽  
Ras Mutations

e22100 Background: Identifying K-ras mutation has became a standard procedure in cancer treatment. Colorectal cancer patients with K-ras mutation are likely to poorly respond to cetuximab. Therefore, detecting K-ras gene mutations should be suggested before the selection of personalized treatment in colorectal cancer. To date, general molecular biology techniques contain HRM, PCR-RFLP, TaqMan PCR and CE-IVD-validated Cobas 4800 KRAS (Roche Diagnostics) are used for K-ras mutation detection in molecular diagnosis, but the sensitivity limitation of these method is approximately 1%. Methods: Therefore, we used a new approach, a universal genetic detecting method (FemtoPath), which improves sensitivity of K-ras mutation detection and the limitation of sensitivity is closed to 0.1% of mutation type. Results: We compared the sensitivity between FemtoPath/direct sequencing test and Cobas KRAS real-time PCR. Cobas real-time PCR identifies mutations in 21 (40.38%) of the 52 tumors. Surprisingly, the FemtoPath/direct sequencing test identified mutations in 40 (76.92%) of the 52 tumors. Our data showed that the FemtoPath/direct sequencing test can identify 19 additional mutation samples. In addition, the FemtoPath/direct sequencing test can identify more unknown K-ras mutations adjacent to codon 12 and 13. Conclusions: Ensure the most timely and appropriate therapy for cancer patients is the first priority of clinical application. FemtoPath/direct sequencing test is more sensitive, accurate and inexpensive and needs fewer sample amount than Cobas real-time PCR.

Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA (ctDNA) in metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1015-1015
Author(s):  
Charlotte Victoria Fribbens ◽  
Isaac Garcia-Murillas ◽  
Matthew Beaney ◽  
Sarah Hrebien ◽  
Karen Howarth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Disease Progression ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Plasma Samples ◽  
First Line ◽  
Ras Mutations ◽  
Esr1 Mutations

1015 Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have a high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Methods: Seventy-one patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study to collect plasma samples for ctDNA analysis every three months on therapy, and at disease progression. All plasma samples were analysed with ESR1 multiplex digital PCR assays, and samples at disease progression were analysed by InVision (enhanced tagged-amplicon sequencing). Mutations were tracked back through samples prior to disease progression to study the evolution of mutations on therapy. Results: Of the 34 patients who progressed on first line AI, 53% (18/34) had ESR1 mutations detectable at progression. Sequencing of progression plasma ctDNA identified polyclonal RAS mutations in 10.7% (3/28) progressing patients (2 polyclonal KRAS, 1 monoclonal HRAS), all of whom also had ESR1 mutations, and a patient with an activating p.R248C FGFR3 mutation. ESR1 mutations were subclonal in 78.6% (11/14) patients, with all RAS mutations being rare subclones. In serial tracking prior to progression, ESR1 mutations were detectable in plasma with a median of 5.3 months (95% CI 2.9-NA) prior to clinical progression. Conclusions: ESR1 mutations are found at high frequency in patients progressing on AI, but are frequently sub-clonal and may not be the sole driver of AI resistance in these patients. Poly-clonal KRAS mutations are identified as a novel mechanism of resistance to AI, associated with detection of ESR1 mutations.

scholarly journals A retrospective observational study to estimate the attrition of patients across lines of systemic treatment for metastatic colorectal cancer in Canada

2019 ◽  
Vol 26 (6) ◽  
Author(s):  
H. Kennecke ◽  
S. Berry ◽  
J. Maroun ◽  
P. Kavan ◽  
N. Aucoin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Systemic Therapy ◽  
Systemic Treatment ◽  
Growth Factor Receptor ◽  
Retrospective Chart Review ◽  
First Line ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
Epidermal Growth

Background Selection and sequencing of treatment regimens for individual patients with metastatic colorectal cancer (mcrc) is driven by maintaining reasonable quality of life and extending survival, as well as by access to and cost of therapies. The objectives of the present study were to describe, for patients with mcrc, attrition across lines of systemic therapy, patterns of therapy and their timing, and KRAS status.Methods A retrospective chart review at 6 Canadian academic centres included sequential patients who were diagnosed with mcrc from 1 January 2009 onward and who initiated first-line systemic treatment for mcrc between 1 January and 31 December 2009. Death was included as a competing risk in the analysis.Results The analysis included 200 patients who started first-line therapy. The proportions of patients who started second-, third-, and fourth-line systemic therapy were 70%, 30%, and 15% respectively. Chemotherapy plus bevacizumab was the most common first-line combination (66%). The most common first-line regimen was folfiri plus bevacizumab. KRAS testing was performed in 103 patients (52%), and 38 of 68 patients (56%, 19% overall) with confirmed KRAS wild-type tumours received an epidermal growth factor receptor inhibitor (egfri), which was more common in later lines. Most KRAS testing occurred after initiation of second-line therapy.Conclusions In the modern treatment era, a high proportion of patients receive at least two lines of therapy for mcrc, but only 19% receive egfri therapy. Earlier KRAS testing and therapy with an egfri might allow a greater proportion of patients to access all 5 active treatment agents.

scholarly journals First-line treatment outcomes according to cfDNA analysis of RAS mutation status in metastatic colorectal cancer (mCRC) patients (pts): PERSEIDA study

2018 ◽  
Vol 29 ◽  
pp. viii183
Author(s):  
P. García Alfonso ◽  
M. Valladares-Ayerbes ◽  
J. Muñoz Luengo ◽  
P. Pimentel ◽  
J.M. Viéitez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Outcomes ◽  
Line Treatment ◽  
First Line ◽  
Ras Mutation ◽  
Mutation Status ◽  
First Line Treatment
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