Recent advances in colorectal cancer (CRC) treatment and screening are offering more precise, biomarker-driven care, according to a series of updates presented throughout February 2026. Developments span the spectrum of the disease, from locally advanced rectal cancer to metastatic disease and screening strategies.
Data released February 19th in the Journal of Clinical Oncology detailed results from the phase III CONVERT trial, comparing neoadjuvant CAPOX (capecitabine and oxaliplatin) to capecitabine-based chemoradiotherapy (nCRT) in locally advanced rectal cancer patients with uninvolved mesorectal fascia on MRI. The trial, involving 589 patients with a median follow-up of 48 months, showed a 3-year locoregional recurrence-free survival (LRRFS) rate of 97.4% for nCRT versus 96.3% for nCT, with a hazard ratio of 1.40 (95% CI, 0.53–3.68). Whereas formal noninferiority wasn’t established, the study indicated comparable survival with potentially less long-term toxicity, as grade 2–4 adverse events were significantly lower with nCT (16.0% vs 26.3%, P = 0.002), and proctitis was less frequent (33.6% vs 41.7%, P = 0.049).
In the realm of metastatic CRC, real-world evidence published February 24th in NEJM Evidence supports the use of trifluridine–tipiracil (FTD–TPI) in combination with bevacizumab. A U.S.-based study utilizing the ConcertAI RWD360 dataset, and building on the phase III SUNLIGHT trial’s findings, analyzed 472 patients in each cohort after propensity score matching. Results showed a median real-world overall survival (rwOS) of 8.9 months with FTD–TPI + bevacizumab compared to 5.8 months with FTD–TPI alone (P < 0.001). Median real-world time to treatment discontinuation (rwTTD) was 3.5 vs 2.2 months, and median real-world time to next treatment or death (rwTTNTD) was 4.9 vs 3.5 months.
The U.S. Food and Drug Administration (FDA) granted traditional approval on February 24th to encorafenib (Braftovi) in combination with cetuximab and fluorouracil-based chemotherapy for patients with metastatic colorectal cancer harboring a BRAF V600E mutation. This approval followed accelerated approval in 2024 and is based on the phase III BREAKWATER trial (NCT04607421). The trial demonstrated a median progression-free survival (PFS) of 12.8 months for the encorafenib combination versus 7.1 months with standard chemotherapy (HR 0.53, 95% CI, 0.41–0.68; p < 0.0001), a median overall survival (OS) of 30.3 months versus 15.1 months (HR 0.49, 95% CI, 0.38–0.63; p < 0.0001), and an objective response rate (ORR) of 61% versus 40% (p = 0.0008). In a cohort utilizing a FOLFIRI backbone, the combination achieved an ORR of 64% versus 39% with FOLFIRI ± bevacizumab (p = 0.0011).
Also in February, the FDA granted Fast Track designation to pelareorep, an investigational immunotherapeutic agent, in combination with bevacizumab and FOLFIRI for second-line treatment of KRAS-mutant, microsatellite-stable (MSS) metastatic colorectal cancer. Early clinical data showed an objective response rate (ORR) of 33% (compared to approximately 10% historically), a median progression-free survival (PFS) of 16.6 months (versus approximately 5.7 months historically), and a median overall survival (OS) of 27 months (versus approximately 11.2 months historically). A planned, controlled study is expected to begin patient enrollment in March 2026.
Research also highlighted the importance of considering liver metastases when treating MSS/pMMR metastatic CRC with immune checkpoint inhibitors (ICIs). A retrospective cohort study published February 18th in Cancer Research Communications found that patients with liver metastases at the initiation of ICI therapy had significantly inferior outcomes, with a clinical benefit rate of 16.1% compared to 46.2% for those without liver metastases (P = 0.001). Median progression-free survival (PFS) was 2.1 months versus 2.5 months (HR 1.68, P = 0.009), and median overall survival (OS) was 6.2 months versus 11.5 months (HR 2.03, P < 0.001).
The Swedish SCREESCO randomized controlled trial, published February 20th in Nature Medicine, compared colonoscopy or two rounds of fecal immunochemical testing (FIT) to usual care in 278,280 60-year-olds. After a median follow-up of 4.8 years, the study found a colonoscopy IRR of 1.08 (95% CI, 0.91–1.28) and a FIT IRR of 0.92 (95% CI, 0.81–1.05) for overall CRC incidence. Stage I–II CRC was more frequently detected with colonoscopy (IRR 1.38, 95% CI 1.09–1.74), while stage III–IV CRC was lower with FIT (IRR 0.71, 95% CI 0.58–0.86).
Further research published in eClinicalMedicine in February examined subsequent primary cancer (SPC) risks in CRC survivors without a known hereditary predisposition. Analysis of 7,202 survivors showed no overall increase in SPC risk, but higher risks were observed for metachronous CRC (IRR 1.34, 95% CI 1.14–1.57) and certain extracolonic sites, including hematopoietic cancers (IRR 2.49, 95% CI 1.92–3.21), liver cancer (IRR 2.25, 95% CI 1.51–3.36), and thyroid cancer (IRR 1.90, 95% CI 1.20–3.02). Early-onset CRC survivors (diagnosed ≤50 years) exhibited a higher overall SPC risk (1.43, 1.25–1.64).
Alphamab Oncology initiated the phase III JSKN003-005 trial on February 14th, evaluating JSKN003, a biparatopic HER2 antibody–drug conjugate, in HER2-positive advanced CRC. The trial will compare JSKN003 to investigator’s choice of later-line therapies. Preliminary data presented at ESMO 2025 showed an objective response rate (ORR) of 68.8% and a median progression-free survival (PFS) of 11.04 months in 32 patients.
A phase II ABACO trial, published in ESMO Gastrointestinal Oncology (March 2026), evaluated cabozantinib in heavily pretreated MSS metastatic CRC. The trial met its primary endpoint, with a 16-week PFS rate of 33% (11/33). Median PFS was 2.27 months (95% CI 1.71–3.65), and median OS was 6.25 months (95% CI 3.81–10.26). Exploratory analyses suggested potential benefit from TP53 mutation status and tumor mutational burden.
Finally, a multicenter Italian study published February 16th in Clinical Colorectal Cancer found that patients with early-onset colorectal cancer (EO-CRC, ≤50 years) experienced inferior outcomes after liver metastasectomy compared to average-onset CRC (AO-CRC, >50 years), with a median overall survival of 44.0 months versus 64.0 months (p < 0.0001).
