P-159 Regorafenib vs TAS-102 as salvage-line treatment in patients with metastatic colorectal cancer refractory to standard chemotherapies: A multicenter retrospective comparison study

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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The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment

Targeted Oncology ◽

10.1007/s11523-021-00816-3 ◽

2021 ◽

Author(s):

Pina Ziranu ◽

Eleonora Lai ◽

Marta Schirripa ◽

Marco Puzzoni ◽

Mara Persano ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Wild Type ◽

P53 Expression

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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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Bevacizumab plus capecitabine as later-line treatment for patients with metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines

Scientific Reports ◽

10.1038/s41598-021-86482-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yeong Hak Bang ◽

Jeong Eun Kim ◽

Ji Sung Lee ◽

Sun Young Kim ◽

Kyu-Pyo Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Median Overall Survival ◽

Treatment Options ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Line Treatment ◽

Free Survival ◽

Medical Need ◽

Significant Disease

AbstractThere is an unmet medical need for later-line treatment options for patients with metastatic colorectal cancer (mCRC). Considering that, beyond progression, co-treatment with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate, we aimed to evaluate the efficacy of capecitabine and bevacizumab. This single-center retrospective study included 157 patients between May 2011 and February 2018, who received bevacizumab plus capecitabine as later-line chemotherapy after progressing with irinotecan, oxaliplatin, and fluoropyrimidines. The study treatment consisted of bevacizumab 7.5 mg/kg on day 1 and capecitabine 1,250 mg/m2 orally (PO) twice daily on day 1 to 14, repeated every 3 weeks. The primary endpoint was progression-free survival (PFS). The median PFS was 4.6 months (95% confidence interval [CI] 3.9–5.3). The median overall survival (OS) was 9.7 months (95% CI 8.3–11.1). The overall response rate was 14% (22/157). Patients who had not received prior targeted agents showed better survival outcomes in the multivariable analysis of OS (hazard ratio [HR] = 0.59, 95% CI 0.43–0.82, P = 0.002) and PFS (HR = 0.61, 95% CI 0.43–0.85, P = 0.004). Bevacizumab plus capecitabine could be a considerably efficacious option for patients with mCRC refractory to prior standard treatments.

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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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