Third-line treatment and beyond in metastatic colorectal cancer: What do we have and what can we expect?

Ayala-de Miguel, Carlos; Jiménez-Castro, Jerónimo; Sánchez-Vegas, Adrián; Díaz-López, Sebastián; Chaves-Conde, Manuel

doi:10.1016/j.critrevonc.2024.104454

Critical Reviews in Oncology/Hematology

2024

DOI: 10.1016/j.critrevonc.2024.104454

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Third-line treatment and beyond in metastatic colorectal cancer: What do we have and what can we expect?

Carlos Ayala-de Miguel,

Jerónimo Jiménez-Castro,

Adrián Sánchez-Vegas

et al.

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2024

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Cited by 3 publications

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The emerging HER2 landscape in colorectal cancer: the key to unveil the future treatment algorithm?

Venturini,

Massaro,

Lavacchi

et al. 2024

Critical Reviews in Oncology/Hematology

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The emerging HER2 landscape in colorectal cancer: the key to unveil the future treatment algorithm?

Venturini,

Massaro,

Lavacchi

et al. 2024

Critical Reviews in Oncology/Hematology

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Profile of Fruquintinib in the Management of Advanced Refractory Metastatic Colorectal Cancer: Design, Development and Potential Place in Therapy

Syaj,

Saeed

2024

DDDT

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Colorectal cancer (CRC) is a prevalent and deadly cancer, with metastatic CRC (mCRC) often leading to poor outcomes despite advancements in screening and chemotherapy. Anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) pathways have become essential in mCRC treatment. Bevacizumab, a VEGF inhibitor, was the first agent used in this context. However, drug resistance prompted the development of more selective inhibitors, such as fruquintinib, a tyrosine kinase inhibitor (TKI) that targets VEGFR-1, −2, and −3. Fruquintinib has shown promise in clinical trials, particularly for third-line mCRC treatment. The Phase III FRESCO trial in China demonstrated its efficacy, significantly improving overall survival (OS) and progression-free survival (PFS) compared to placebo, with manageable safety concerns like hypertension and hand-foot skin reactions. The FRESCO-2 trial extended these findings to European and North American populations, leading to a recent FDA approval for previously treated mCRC patients. The pharmacodynamic profile of fruquintinib includes potent inhibition of VEGFR, angiogenesis, and lymphangiogenesis. It has shown synergistic effects when combined with other treatments like chemotherapy and immune checkpoint inhibitors (ICIs). Current research focuses on exploring fruquintinib’s combination with ICIs, such as PD-1 inhibitors, to enhance treatment efficacy, especially in microsatellite stable (MSS) CRC. Ongoing trials are investigating Fruquintinib’s potential in combination with other therapies and its use in earlier lines of treatment. While promising, further studies are required to optimize its place in therapy and identify predictive biomarkers for better patient selection.

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Survival Outcomes with Regorafenib and/or Trifluridine/Tipiracil Sequencing to Rechallenge with Third-Line Regimens in Metastatic Colorectal Cancer: A Multicenter Retrospective Real-World Subgroup Comparison from the ReTrITA Study

Signorelli,

Calegari,

Anghelone

et al. 2024

Current Oncology

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Background: There is ongoing discussion around the optimal course of treatment for metastatic colorectal cancer (mCRC) following the second line. Trifluridine/tipiracil (T) and regorafenib (R) have been the mainstay of therapy in this situation, as they both increased overall survival (OS) in comparison to a placebo. Despite the paucity of evidence, therapy rechallenge is also recognized as an option for practical use. In the third-line scenario of mCRC, we planned to investigate the survival outcomes using (T) and (R), both with and without prior rechallenge treatment. Materials and methods: Between 2012 and 2023, we examined the medical records of 1156 patients with refractory mCRC who were enrolled in the multicenter retrospective ReTrITA study. We then separated the patients into two cohorts based on the rechallenge therapy that was given before regorafenib and/or trifluridine/tipiracil at 17 Italian centres. Results: A total of 981 patients underwent T and/or R therapy, while 175 patients had therapy rechallenge before T and/or R. The median overall survival (mOS) for patients treated with T/R and R/T sequences in the rechallenge therapy cohort was 14.5 months and 17.6 months, respectively (p = 0.1955). A statistically significant survival benefit was observed in patients who received monotheraphy with R (mOS: 6 months) compared to the T group (mOS: 4.2 months) (p = 0.0332). In the same cohort, a median progression-free survival (mPFS) benefit was demonstrated in favour of the R/T group (11.3 months) vs. 9 months of the reverse sequence (p = 0.4004). In the no-rechallenge cohort, the mOS was statistically longer in the R/T sequence than in the T/R sequence (16.2 months vs. 12.3 months, respectively; p = 0.0014). In terms of the mPFS, we saw the same significant result for the adoption of R/T treatment (11.5 months vs. 8.4 months, respectively; p < 0.0001). The two monotherapy groups did not reveal any significant differences. Conclusions: This study suggests that rechallenge therapy may improve survival rates in the third-line treatment of mCRC, particularly if it is administered before sequential R/T treatment. This could allow for the extension of mCRC treatment choices until prospective studies are finished or randomised trials are performed.

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Third-line treatment and beyond in metastatic colorectal cancer: What do we have and what can we expect?

Cited by 3 publications

References 122 publications

The emerging HER2 landscape in colorectal cancer: the key to unveil the future treatment algorithm?

The emerging HER2 landscape in colorectal cancer: the key to unveil the future treatment algorithm?

Profile of Fruquintinib in the Management of Advanced Refractory Metastatic Colorectal Cancer: Design, Development and Potential Place in Therapy

Survival Outcomes with Regorafenib and/or Trifluridine/Tipiracil Sequencing to Rechallenge with Third-Line Regimens in Metastatic Colorectal Cancer: A Multicenter Retrospective Real-World Subgroup Comparison from the ReTrITA Study

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