TRIAL DATA

Adding immunotherapy to chemotherapy before surgery in stage III colon cancer — Clinical Colorectal Cancer

The AZUR-4 trial is a Phase 2, open label, randomized study of neoadjuvant dostarlimab plus CAPEOX versus CAPEOX in previously untreated T4N0 or stage III mismatch repair proficient/microsatellite stable resectable colon cancer.

If you have stage III colon cancer that is MSS or pMMR, ask your oncologist whether this trial might be appropriate for you.

TREATMENT

Encorafenib and cetuximab re-challenge combined with nivolumab in BRAF-mutated colorectal cancer — Clinical Colorectal Cancer

A case report from the AGMT mCRC Registry documented successful encorafenib and cetuximab re-challenge combined with nivolumab in BRAF V600E mutated, mismatch-repair-proficient metastatic colorectal cancer.

If you have BRAF V600E-mutated colorectal cancer that previously responded to targeted therapy, this case suggests that re-treatment with the same combination plus immunotherapy may be worth discussing with your care team.

TRIAL DATA

Testing immunotherapy combination in MSS metastatic colorectal cancer — Clinical Colorectal Cancer

A Phase II study of pembrolizumab plus capecitabine and bevacizumab for microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.

Most colorectal cancers are MSS/pMMR and don't respond well to immunotherapy alone. This trial is testing whether combining immunotherapy with chemotherapy and bevacizumab can help these tumors respond. Results from this Phase 2 study will help determine whether this approach should be tested in larger trials.

TREATMENT

Metronomic chemotherapy plus regorafenib tested in treatment-resistant metastatic colorectal cancer — ESMO Gastrointestinal Oncology

The REPROGRAM-01 single-arm phase II trial tested regorafenib combined with metronomic capecitabine, cyclophosphamide, and aspirin in refractory metastatic colorectal cancer. This approach aims to improve outcomes in heavily pre-treated patients by combining different mechanisms of action.

For patients whose cancer has progressed through multiple lines of treatment, this combination approach may offer a new option. The gradual dose escalation strategy for regorafenib may also help manage side effects better than standard dosing.

🧬 Biomarker Spotlight

Research by genetic subtype — KRAS, BRAF, MSI-H, and more

Anti-malaria drug may help overcome KRAS-driven resistance to immunotherapy — Cell Death & Disease

Laboratory research identified KRAS mutation as associated with resistance to regorafenib plus anti-PD-1 in colorectal cancer liver metastases. Dihydroartemisinin (DHA), a clinically approved anti-malaria agent, was verified to selectively downregulate KRASG12D mutant with no discernible influences on wild-type KRAS. In preclinical KRASG12D colorectal cancer liver metastases models, DHA showed promise in combination with regorafenib plus anti-PD-1.

This is early-stage laboratory research, not yet tested in patients. If you have KRAS-mutated colorectal cancer with liver metastases, this research suggests potential future treatment strategies, but clinical trials in humans are needed first.

Rare NRAS G12C mutation responds to KRAS inhibitor plus EGFR blockade — Cureus

A case report documented an objective tumor response to sotorasib (a KRAS G12C inhibitor) combined with panitumumab (an EGFR blocker) in a patient with advanced, NRAS G12C-mutated, mismatch repair-deficient rectal cancer who had developed local recurrence after neoadjuvant therapy and whose disease was refractory to immunotherapy. NRAS G12C mutations are exceptionally rare in colorectal cancer.

This single-patient case suggests that KRAS G12C inhibitors may work against the related NRAS G12C mutation. If you have NRAS G12C-mutated colorectal cancer, discuss with your oncologist whether this off-label treatment approach might be an option.

Real-world mutation patterns in Chilean colorectal cancer patients — Journal of Gastrointestinal Oncology

A study analyzed real-world molecular data from 999 patients with colorectal cancer diagnosed between 2019 and 2021 across multiple Chilean institutions to characterize the frequency and sex-specific distribution of KRAS, NRAS, and BRAF mutations. The analysis included patients across all stages and reflects real-world molecular testing patterns in Chile.

🔎 Screening Watch

Screening guidelines, early detection, and prevention advances

Liquid biopsy for colorectal cancer screening: promise and limitations — Intestinal Research

A review examined the potential of liquid biopsy—analyzing tumor-derived components in blood such as circulating tumor cells, circulating tumor DNA, and tumor-derived extracellular vesicles—for colorectal cancer screening. Early studies have suggested the feasibility of colorectal cancer detection; however, its sensitivity for the detection of advanced adenomas remains limited. To date, no adequately powered randomized trial has demonstrated that liquid biopsy-based screening reduces the rate of colorectal cancer-specific mortality.

Blood-based screening tests are promising but not yet proven to save lives or catch precancerous polyps as effectively as colonoscopy. Continue following current screening guidelines—colonoscopy remains the gold standard for both detection and prevention.

AZUR-4: Immunotherapy before surgery in stage III colon cancer

A Phase 2, open label, randomized study of neoadjuvant dostarlimab plus CAPEOX versus CAPEOX in previously untreated T4N0 or stage III mismatch repair proficient/microsatellite stable resectable colon cancer. Clinical Colorectal Cancer

Pembrolizumab combination in MSS/pMMR metastatic disease

A Phase II study of pembrolizumab plus capecitabine and bevacizumab for microsatellite stable/mismatch repair-proficient metastatic colorectal cancer. Clinical Colorectal Cancer

REPROGRAM-01: Metronomic chemotherapy plus regorafenib

A single-arm phase II trial testing regorafenib combined with metronomic capecitabine, cyclophosphamide, and aspirin in refractory metastatic colorectal cancer. ESMO Gastrointestinal Oncology

999 patients

Real-world molecular data from Chilean colorectal cancer patients analyzed for KRAS, NRAS, and BRAF mutation patterns. This type of real-world evidence helps researchers understand how mutation patterns vary across different populations and can inform treatment strategies in diverse patient groups.

Understanding Biomarker Testing

Many of this week's findings involve specific genetic mutations like KRAS, BRAF, and MSI status. The Colorectal Cancer Alliance offers a comprehensive guide to biomarker testing that explains what these tests are, why they matter, and how they guide treatment decisions.

Visit the Colorectal Cancer Alliance Biomarker Testing Guide →

Questions to bring to your next appointment based on this week's research:

  • Has my tumor been tested for mismatch repair status (MMR) and microsatellite instability (MSI)? If it's MSS/pMMR, are there any clinical trials testing immunotherapy combinations that might be appropriate for me?
  • If my tumor has a KRAS, NRAS, or BRAF mutation, what targeted therapy options are available, and are there any trials testing new combinations for my specific mutation?
  • If I've already been through multiple lines of treatment, what are my options for later-line therapy, and should we consider approaches like metronomic chemotherapy or clinical trials?