This Week in CRC Research

TRIAL DATA

Adding immunotherapy to intensive chemotherapy shows promise in hard-to-treat colorectal cancer — Nature Communications

The phase II NIVACOR trial tested nivolumab (an immunotherapy drug) combined with FOLFOXIRI/bevacizumab chemotherapy as first-line treatment in patients with RAS or BRAF-mutated metastatic colorectal cancer. These mutations are found in tumors that typically don't respond well to immunotherapy alone. The study enrolled patients whose tumors were proficient mismatch repair (pMMR) or microsatellite stable (MSS) — the majority of colorectal cancers that are generally resistant to immune checkpoint inhibitors.

What this means

This trial explores whether combining immunotherapy with intensive chemotherapy can overcome resistance in tumors that don't typically respond to immunotherapy. Results may help identify which patients with RAS or BRAF mutations could benefit from this combination approach.

TRIAL DATA

Long-term results show benefit of chemotherapy after liver metastasis surgery — Journal of Clinical Oncology

The JCOG0603 trial compared hepatectomy (liver surgery) followed by mFOLFOX6 chemotherapy versus hepatectomy alone for patients with liver metastases from colorectal cancer. This phase II/III randomized trial now reports long-term outcomes, providing evidence on whether adjuvant chemotherapy after complete surgical removal of liver metastases improves survival.

What this means

For patients who have colorectal cancer that has spread to the liver and can be surgically removed, this study helps answer whether chemotherapy after surgery provides additional benefit. The long-term results can guide treatment decisions for this patient population.

TRIAL DATA

Chemotherapy alone may be as effective as chemoradiation before rectal cancer surgery — Journal of Clinical Oncology

The CONVERT trial compared neoadjuvant chemotherapy with CAPOX (capecitabine and oxaliplatin) versus chemoradiation for locally advanced rectal cancer with uninvolved mesorectal fascia. This phase III trial reports final results on whether chemotherapy alone before surgery can achieve similar outcomes to the standard approach of chemoradiation, potentially sparing patients radiation-related side effects.

What this means

For patients with locally advanced rectal cancer where the tumor hasn't reached the outer layer of tissue around the rectum, chemotherapy alone before surgery might be an option instead of chemoradiation. This could reduce radiation-related side effects while maintaining treatment effectiveness.

TREATMENT

Real-world data compares late-line treatment options for metastatic colorectal cancer — ESMO Open

A multicenter study compared outcomes of trifluridine/tipiracil (FTD-TPI) plus bevacizumab versus FTD-TPI alone or regorafenib in patients with pretreated metastatic colorectal cancer. The analysis included real-world data on effectiveness and examined whether KRAS G12 mutations affect FTD-TPI efficacy. These are treatment options typically used after standard chemotherapy regimens have stopped working.

What this means

For patients whose cancer has progressed after multiple treatments, this study provides real-world evidence comparing available late-line therapy options. Understanding how these treatments perform outside clinical trials helps patients and doctors make informed decisions about next steps.

SCREENING

Blood-based DNA tests show promise for colorectal cancer screening — Critical Reviews in Oncology/Hematology

A systematic review and meta-analysis evaluated the diagnostic accuracy of blood-based circulating tumor DNA (ctDNA) tests for detecting advanced colorectal neoplasia in asymptomatic, average-risk populations. The analysis examined how well these minimally invasive blood tests can identify advanced adenomas and colorectal cancer compared to traditional screening methods like colonoscopy and stool-based tests.

What this means

Blood-based screening tests could offer a convenient alternative to colonoscopy or stool tests for people at average risk. While still being validated, these tests may increase screening participation by providing a simple blood draw option, though their ability to detect precancerous polyps needs further study.

🔬 Under 50 Spotlight

Research relevant to early-onset and younger CRC patients

Study examines symptom patterns in people ages 42-49 before colorectal cancer diagnosis — Cancer Epidemiology, Biomarkers & Prevention

Researchers identified patients ages 42-49 in three health systems between 2012-2020 whose first recorded colonoscopy led to colorectal cancer diagnosis. The study calculated the positive predictive value of symptoms as indicators of early-onset colorectal cancer, providing data on which symptoms in younger adults are most likely to indicate cancer.

Screening rates remain low among adults aged 45-49 despite new guidelines — The American Journal of Managed Care

Using 2023 National Health Interview Survey data, researchers found that colorectal cancer screening rates among adults aged 45-49 were significantly lower than rates among adults aged 50-54, despite updated recommendations to begin screening at age 45. The study identified predictors of screening uptake in this younger age group.

🧬 Biomarker Spotlight

Research by genetic subtype — KRAS, BRAF, MSI-H, HER2, and more

Guidelines recommend repeat molecular testing during metastatic colorectal cancer treatment — Cancers

A review examined the evolving role of repeat molecular testing in metastatic colorectal cancer. While NCCN and ASCO recommend initial testing for RAS, BRAF, HER2, and MSI/MMR status, this analysis discusses when and why repeat testing during treatment may identify new mutations or changes that could guide therapy decisions.

Case report: Re-challenge with BRAF-targeted therapy plus immunotherapy shows response — Clinical Colorectal Cancer

Researchers reported a patient with BRAF V600E mutated, mismatch-repair-proficient metastatic colorectal cancer who responded to re-challenge with encorafenib and cetuximab combined with nivolumab after initial treatment. This case from the AGMT mCRC Registry suggests that combining BRAF-targeted therapy with immunotherapy may be effective even in tumors that are typically resistant to immunotherapy.

Review summarizes molecular targeting advances for EGFR, BRAF, and HER2 in colorectal cancer — Journal of Clinical Medicine

A comprehensive review examined contemporary advances in molecular targeting of EGFR, BRAF, and HER2 signaling pathways in metastatic colorectal cancer, focusing on panitumumab, encorafenib, and tucatinib. The review discusses how molecular profiling enables biomarker-driven treatment strategies based on RAS, BRAF V600E, and HER2 alterations.

Clinical Trials Update

Phase II trial tests pembrolizumab plus chemotherapy in MSS colorectal cancer — Clinical Colorectal Cancer

A phase II study evaluated pembrolizumab combined with capecitabine and bevacizumab in patients with microsatellite stable/mismatch repair-proficient metastatic colorectal cancer. This trial addresses the challenge that most colorectal cancers (MSS/pMMR) don't respond well to immunotherapy alone.

AZUR-4 trial compares neoadjuvant immunotherapy plus chemotherapy versus chemotherapy alone — Clinical Colorectal Cancer

This phase II randomized study (AZUR-4) is comparing dostarlimab plus CAPEOX versus CAPEOX alone as neoadjuvant treatment in previously untreated T4N0 or stage III mismatch repair proficient/microsatellite stable resectable colon cancer. The trial tests whether adding immunotherapy before surgery improves outcomes in tumors that typically don't respond to immunotherapy.

FIERCE study assesses safety of trifluridine/tipiracil with radiation before rectal cancer surgery — Clinical Colorectal Cancer

The phase Ib FIERCE study evaluated the safety of neoadjuvant trifluridine/tipiracil with concurrent radiation in resectable stage II/III rectal cancer. This trial explores whether this oral chemotherapy drug can be safely combined with radiation therapy before surgery.

RECAST trial compares two first-line regimens with ramucirumab for metastatic colorectal cancer — European Journal of Cancer

The randomized phase II WJOG9216G (RECAST) study compared FOLFIRI plus ramucirumab versus FOLFOXIRI plus ramucirumab as first-line treatment for metastatic colorectal cancer. The trial examines whether the more intensive FOLFOXIRI regimen combined with ramucirumab offers advantages over the standard FOLFIRI combination.

By the Numbers

60-83%

Five-year overall survival rates achieved in highly selected patients with unresectable colorectal cancer liver metastases who underwent liver transplantation, according to prospective trials reviewed in Cancers. The Oslo score helps identify optimal candidates for this emerging treatment approach, which represents a paradigm shift in transplant oncology beyond hepatocellular carcinoma.

Resources

Colorectal Cancer Alliance: Biomarker Testing Guide

The Colorectal Cancer Alliance offers a comprehensive guide to understanding biomarker testing, including RAS, BRAF, HER2, and MSI/MMR status. This resource helps patients understand why testing matters and how results guide treatment decisions.

Visit Resource →