Second line FOLFOX4 and bevacizumab for metastatic colorectal cancer: Real life efficacy and predictive factors

The addition of aflibercept to FOLFIRI has been demonstrated to improve survival in patients with metastatic colorectal cancer (mCRC) who progressed after receiving a standard oxaliplatin-based regimen. In this retrospective, single-institution, observational study we collected clinical data from mCRC patients who received aflibercept in combination with FOLFIRI in routine clinical practice from October 2012 to March 2021 to describe feasibility and efficacy of this regimen in a real-world population. Forty-nine patients receiving aflibercept-FOLFIRI as second-line treatment were identified, 40.8% of whom were aged over 65 years. The majority of patients had multi-organ metastases (73.5%), and had previously received bevacizumab in combination with chemotherapy (CT) as first-line treatment (79.6%). Median overall survival (OS) and progression-free survival (PFS) were 13 and 6 months, respectively; overall response rate (ORR) and disease control rate (DCR) were 12.3% and 49.1%, respectively. Several factors were associated with survival in univariate analysis, including PFS in first-line therapy, number of metastatic sites, bone metastases and others. However, in multivariate analysis, but only PFS in first-line CT over 12 months was significantly associated with better OS (HR 0.32; 95% CI 0.13–0.79; p = 0.01). Hypertension was the most commonly reported grade (G) 3–4 adverse event (AE), affecting 18.4% of the overall population. Thromboembolic events were observed in 16.3% of patients, hemorrhagic events in 10.2%, and proteinuria in 8.2%. Neutropenia was the most frequently observed hematological G3–4 AE with an incidence of 10.2%. Aflibercept-FOLFIRI has been confirmed as a feasible second-line treatment for mCRC in a real-life setting, and PFS in first-line therapy >12 months resulted as the only predictive marker of better survival.

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Metastatic Colorectal Cancer: Prognostic and Predictive Factors

Current Medicinal Chemistry ◽

10.2174/0929867326666190620110732 ◽

2020 ◽

Vol 27 (17) ◽

pp. 2779-2791 ◽

Cited By ~ 1

Author(s):

Anna Nappi ◽

Guglielmo Nasti ◽

Carmela Romano ◽

Massimiliano Berretta ◽

Alessandro Ottaiano

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Predictive Factors ◽

Cancer Biology ◽

Clinical Course ◽

Molecular Signatures ◽

Biological Drugs ◽

The Third ◽

Therapeutic Context ◽

Prognostic And Predictive Factors

: Colorectal cancer represents the third most frequently occurring cancer worldwide. In the last decade, the survival of patients affected by metastatic colorectal cancer (mCRC) has improved through the introduction of biological drugs. However, in this new and dynamic therapeutic context, research about prognostic and predictive factors is important to guide the oncologists to effective therapies as well as to improve the understanding of colorectal cancer biology. Their identification is an intensive area of research and our future goal will be to depict tumour-specific "molecular signatures" in order to predict the clinical course of the disease and the best treatments. : In this report, we describe clinical, pathological and molecular biomarkers that can play a role as prognostic or predictive factors in mCRC.

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Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190119162352 ◽

2019 ◽

Vol 21 (10) ◽

pp. 718-724 ◽

Cited By ~ 2

Author(s):

Wen-Cong Ruan ◽

Yue-Ping Che ◽

Li Ding ◽

Hai-Feng Li

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Clinical Prognosis ◽

Line Therapy ◽

Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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Predictive factors of severe early treatment-related toxicity in patients receiving first-line treatment for metastatic colorectal cancer: Pooled analysis of 2190 patients enrolled in Fédération Francophone de Cancérologie Digestive (FFCD) trials

European Journal of Cancer ◽

10.1016/j.ejca.2021.04.040 ◽

2021 ◽

Vol 153 ◽

pp. 40-50

Author(s):

Clémence Breton ◽

Thomas Aparicio ◽

Karine Le Malicot ◽

Michel Ducreux ◽

Thierry Lecomte ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Predictive Factors ◽

Early Treatment ◽

Pooled Analysis ◽

Line Treatment ◽

First Line ◽

Cancérologie Digestive ◽

First Line Treatment

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172PD Final analysis: Phase II trial of irinotecan/S-1/cetuximab (IRIS/Cet) as second line treatment in patients with KRAS exon2 wild type metastatic colorectal cancer: HGCSG0902. Comparison of administration interval in cetuximab treatment

Annals of Oncology ◽

10.1016/s0923-7534(21)00330-6 ◽

2016 ◽

Vol 27 ◽

pp. ix54

Author(s):

T. Ando ◽

S. Yuki ◽

H. Nakatsumi ◽

T. Muranaka ◽

A. Hosokawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Final Analysis ◽

Line Treatment ◽

Second Line ◽

Wild Type ◽

Analysis Phase ◽

Administration Interval

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Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

International Journal of Molecular Sciences ◽

10.3390/ijms22147717 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7717

Author(s):

Guido Giordano ◽

Pietro Parcesepe ◽

Giuseppina Bruno ◽

Annamaria Piscazzi ◽

Vincenzo Lizzi ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Checkpoint Inhibitors ◽

Line Treatment ◽

Second Line ◽

Wild Type ◽

First Line ◽

Braf Mutations ◽

Mutational Status ◽

First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

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