A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer

In the UK, Trifluridine-tipiracil (Lonsurf) is used to treat metastatic colorectal cancer in the third-line setting, after prior exposure to fluoropyrimidine-based regimes. Current data on the real-world use of Lonsurf lack long-term follow-up data. A retrospective evaluation of patients receiving Lonsurf at our Cancer Centre in 2016–2017 was performed, all with a minimum of two-year follow-up. Fifty-six patients were included in the review. The median number of cycles of Lonsurf administered was 3. Median follow-up was 6.0 months, with all patients deceased at the time of analysis. Median progression-free survival (PFS) was 3.2 months, and overall survival (OS) was 5.8 months. The median interval from Lonsurf discontinuation to death was two months, but seven patients received further systemic treatment and median OS gained was 12 months. Lonsurf offered a slightly better PFS but inferior OS to that of the RECOURSE trial, with PFS similar to real-world data previously presented. Interestingly, 12.5% had a PFS > 9 months, and this cohort had primarily left-sided and RAS wild-type disease. A subset received further systemic treatment on Lonsurf discontinuation with good additional OS benefit. Lonsurf may alter the course of disease for a subset of patients, and further treatment on progression can be considered in carefully selected patients.

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Tumor bulk as a prognostic biomarker and predictor of benefit from anti-EGFR therapy in patients with metastatic colorectal cancer: Analysis of 476 patients from the ARCAD Clinical Trials Program.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.108 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 108-108

Author(s):

Benjamin Adam Weinberg ◽

Manel Rakez ◽

Benoist Chibaudel ◽

Tim Maughan ◽

Richard Adams ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Primary Tumor ◽

Lung Metastases ◽

Performance Status ◽

Progression Free Survival ◽

Predictive Biomarker ◽

Wild Type ◽

Cox Models ◽

Study Results

108 Background: Primary tumor sidedness has emerged as a prognostic and predictive biomarker for patients (pts) with metastatic colorectal cancer (mCRC). Tumor bulk has also been postulated to predict response to anti-EGFR therapy. We sought to evaluate the role of tumor bulk as a predictive biomarker to anti-EGFR therapy in pts with left- (LS) and right-sided (RS) mCRC. Methods: Data from 476 pts with mCRC enrolled across 2 first-line trials of anti-EGFR plus chemotherapy versus chemotherapy were pooled. Pts were included if there was available information on tumor sidedness and tumor bulk. All were KRAS wild-type and BRAF wild-type or unknown BRAF status. The right colon was defined as the cecum through the transverse colon, and the left colon as the splenic flexure through the rectum. Tumor bulk was the mean tumor size of target lesions at baseline, bulky defined as > 3.5 cm. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for performance status (PS), platelet count, primary tumor (PT) resection, number of metastatic sites, and stratified by study. Results: Pts with bulky tumors (211, 44%) had higher PS, white blood cell and platelet counts, higher CEA, fewer sites of metastatic disease, more liver than lung metastases, and fewer had PT resection. OS and PFS medians in months (mos) are presented in the table with 95% confidence intervals (95%CIs). Bulky tumors had inferior median OS compared with non-bulky (mOS, 17.9 vs. 21.3 mos, HRadj 1.33, 95% CI 1.05-1.69, P = 0.016) although median PFS was similar (mPFS, 8.6 vs. 8.7 mos, HRadj 1.15, 95% CI 0.92-1.42, P = 0.21). Conclusions: Tumor bulk is an independent prognostic factor for OS in KRAS wild-type and BRAF wild-type or unknown BRAF status pts. Pts with non-bulky RS tumors have survival outcomes similar to pts with bulky LS tumors. Although the mPFS for pts with RS tumors treated with anti-EGFR therapy was the lowest across subgroups, this finding was not statistically significant. Further research is warranted into whether pts with bulky RS tumors benefit from anti-EGFR therapy. Clinical trial information: NCT00182715, NCT00640081. [Table: see text]

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Trajectory of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) predicts time to progression (TTP) in metastatic colorectal cancer (mCRC) patients

Annals of Oncology ◽

10.1093/annonc/mdy300.052 ◽

2018 ◽

Vol 29 ◽

pp. viii619

Author(s):

S.A. Kurk ◽

R.K. Stellato ◽

P.H.M. Peeters ◽

M. Oskam ◽

B.D. Dorresteijn ◽

...

Keyword(s):

Colorectal Cancer ◽

Skeletal Muscle ◽

Metastatic Colorectal Cancer ◽

Systemic Treatment ◽

Time To Progression ◽

Skeletal Muscle Index

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Circulating tumor DNA by next generation sequencing as a prognostic and predictive biomarker in metastatic colorectal cancer

Annals of Oncology ◽

10.1093/annonc/mdy281.098 ◽

2018 ◽

Vol 29 ◽

pp. viii184-viii185

Author(s):

N. Jia ◽

L. Chang ◽

X. Dou ◽

M. Guan ◽

Y. Shao ◽

...

Keyword(s):

Colorectal Cancer ◽

Next Generation Sequencing ◽

Metastatic Colorectal Cancer ◽

Predictive Biomarker ◽

Circulating Tumor Dna ◽

Next Generation ◽

Tumor Dna ◽

Generation Sequencing

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AXL has a prognostic role in metastatic colorectal cancer (mCRC) and is a predictive biomarker of lack of efficacy of chemotherapy (CT) + cetuximab in RAS wild type (WT) patients (pts)

Annals of Oncology ◽

10.1093/annonc/mdy269.094 ◽

2018 ◽

Vol 29 ◽

pp. viii30 ◽

Cited By ~ 1

Author(s):

C. Cardone ◽

B. Blauensteiner ◽

V. Moreno-Viedma ◽

M.C. Paul ◽

G. Martini ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Predictive Biomarker ◽

Wild Type ◽

Prognostic Role

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Optimal duration of systemic treatment in metastatic colorectal cancer

Current Opinion in Oncology ◽

10.1097/cco.0000000000000087 ◽

2014 ◽

Vol 26 (4) ◽

pp. 448-453 ◽

Cited By ~ 7

Author(s):

Lieke H.J. Simkens ◽

Miriam Koopman ◽

Cornelis J.A. Punt

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Systemic Treatment ◽

Optimal Duration

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Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-refractory patients with EGFR-positive advanced and/or metastatic colorectal cancer: Evaluation of the efficacy and safety based on KRAS mutation status (T- CORE0801).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.573 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 573-573

Author(s):

H. Shimodaira ◽

H. Soeda ◽

M. Gamoh ◽

H. Andoh ◽

T. Yamaguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Prospective Study ◽

Metastatic Colorectal Cancer ◽

Response Rate ◽

Objective Response ◽

Antibody Therapy ◽

Predictive Biomarker ◽

Japanese Patients ◽

Efficacy And Safety ◽

Kras Mutations

573 Background: Activating mutation of the KRAS gene is a predictive biomarker for loss of efficacy to anti-EGFR antibody therapy. However, this was mainly established by the evidences of Caucasian studies. Then, this prospective study investigated the role of KRAS mutations on efficacy and safety to cetuximab plus irinotecan in Japanese patients with metastatic colorectal cancer (mCRC). Methods: We conducted a prospective study to analyze objective response to cetuximab plus irinotecan in molecularly defined KRAS wild-type (WT) or mutant subgroups of chemotherapy-refractory mCRC. KRAS mutations were detected by direct sequence on DNA from formalin-fixed, paraffin-embedded tissue of patients treated in 11 centers in Japan. Additional EGFR related genes such as BRAF, PIK3CA etc. and antibody-dependent cellular cytotoxicity related polymorphism in FCγRIIa and RIIIa genes were also examined. Results: Forty-three patients were enrolled. KRAS mutations were found in 31.7% of 41 eligible patients. Response rate (RR) to cetuximab plus irinotecan, the primary endpoint of the study, was 17.9% and 0% for the patients with tumor harboring WT and mutant KRAS, respectively. No significant differences in toxicity were observed between the KRAS WT and mutant groups. Detail statistical analyses are ongoing. Conclusions: We confirmed that KRAS status is a useful predictive maker for the efficacy to cetuximab plus irinotecan therapy in Japanese mCRC patients, even though the response rate in the KRAS WT group was lower than expected. [Table: see text]

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