July 12, 2024

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Breakthroughs in Colorectal Cancer Treatment: Three New Therapies

Breakthroughs in Colorectal Cancer Treatment: Three New Therapies Show Significant Survival Benefits



Breakthroughs in Colorectal Cancer Treatment: Three New Therapies Show Significant Survival Benefits

Progress or Death Risk Reaches 51%! Three New Therapies Bring Multiple Survival Benefits in Colorectal Cancer Treatment.

Metastatic colorectal cancer is a heterogeneous disease associated with poor prognosis. Over the past decade, the dual-target tyrosine kinase inhibitor regorafenib and the chemotherapy drug trifluridine-tipiracil (FTD/TPI) have been the standard treatment for refractory metastatic colorectal cancer patients. Both drugs were approved based on global, placebo-controlled phase 3 trials, which demonstrated statistically significant improvements in overall survival (OS) compared to placebo.

However, the benefits provided by these drugs are limited, and there is an unmet need for additional treatment options, improved OS, and reduced adverse reactions in advanced patients.

Three trials published in 2023 have helped change clinical practice and address these needs. The relevant research was recently published in Nature Reviews Gastroenterology & Hepatology.

Breakthroughs in Colorectal Cancer Treatment: Three New Therapies Show Significant Survival Benefits

FTD/TPI + Bevacizumab Treatment Extends Median OS by 3.3 Months

The SUNLIGHT trial, published in NEJM, included patients with refractory metastatic colorectal cancer who experienced disease progression or intolerance to second-line treatment, had known RAS status, an ECOG PS of 0-1, and histologically confirmed metastatic colorectal cancer. A total of 492 patients were randomly assigned in a 1:1 ratio to receive FTD/TPI + bevacizumab (n=246) combination therapy or FTD/TPI alone (n=246). The trial met its primary endpoint, demonstrating a statistically significant improvement in OS, with a median OS absolute extension of 3.3 months (10.8 months in the experimental group and 7.5 months in the control group; HR 0.61, 95% CI 0.49–0.77, P<0.001).

Fruquintinib Treatment Extends Median OS by Nearly 3 Months

Fruquintinib is a highly selective oral inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3. Based on the positive results of the FRESCO trial conducted in China, the global, placebo-controlled phase 3 trial FRESCO-2 further investigated the tyrosine kinase inhibitor fruquintinib.

This trial included patients aged ≥18 years (≥20 years for Japanese patients) with histologically or cytologically confirmed metastatic colorectal adenocarcinoma, who had received all standard chemotherapy and targeted treatment regimens, experienced progression during FTD/TPI or regorafenib treatment, or were intolerant to the respective drug. A total of 691 patients were randomly assigned in a 2:1 ratio to receive fruquintinib (n=461) or placebo (n=230) treatment. The trial achieved its primary endpoint, demonstrating a statistically significant improvement in OS, with a median OS absolute extension of 2.6 months (7.4 months in the fruquintinib group and 4.8 months in the placebo group; HR 0.66, 95% CI 0.55–0.80, P<0.0001).

Treatment with 960 mg and 240 mg Sotorasib Reduces Disease Progression or Death Risk by 51% and 42%, Respectively

Sotorasib selectively and irreversibly inhibits the KRAS G12C protein. How effective is Sotorasib + anti-EGFR monoclonal antibody panitumumab in treating metastatic colorectal cancer? The CodeBreaK 300 trial, published in NEJM, investigated this. The study included 160 patients with KRAS G12C mutation, chemotherapy-refractory metastatic colorectal cancer who had not received KRAS G12C inhibitor treatment. Patients were randomly assigned in a 1:1:1 ratio to one of the following three regimens:

  • 960 mg Sotorasib group: sotorasib (960 mg, once daily) + panitumumab (n=53);
  • 240 mg Sotorasib group: sotorasib (240 mg, once daily) + panitumumab (n=53);
  • Standard treatment group: investigator-selected standard treatment, including FTD/TPI or regorafenib (n=54).

After a median follow-up of 7.8 months, patients in the 960 mg Sotorasib group and 240 mg Sotorasib group had a median progression-free survival (PFS) of 5.6 months and 3.9 months, respectively, compared to 2.2 months in the standard treatment group. Both doses of the sotorasib combination significantly extended patients’ PFS compared to standard treatment, meeting the primary endpoint.

Compared to the standard treatment group, patients in the 960 mg Sotorasib group had a 51% lower risk of disease progression or death (HR=0.49; 95% CI 0.30–0.80; P=0.006), and patients in the 240 mg Sotorasib group had a 42% lower risk (HR=0.58; 95% CI 0.36–0.93; P=0.03).

In conclusion, these key research advances published in 2023 bring new options for the treatment of metastatic colorectal cancer.

Breakthroughs in Colorectal Cancer Treatment: Three New Therapies Show Significant Survival Benefits


References:

[1] Lonardi S, et al., (2023). New options for late-line treatment of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol, doi:10.1038/s41575-023-00881-1

(source:internet, reference only)

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