Treatment options for colon cancer
Executive summary
Colon cancer treatment now spans surgery, systemic chemotherapy, targeted drugs, immunotherapy and liver-directed approaches, with precision testing guiding choices; recent Phase 3 data add new first-line options for molecular subgroups such as BRAF V600E and dMMR/MSI‑H metastatic disease [1] [2]. Clinical trials and specialized modalities—HAI, novel immunotherapy combinations, and investigational targeted agents—are expanding options but often apply only to biomarker‑defined subsets or require specialized centers [3] [4].
1. Surgery and curative local therapy remain foundational for early disease
For localized colon cancers, surgical removal—ranging from polypectomy or local excision for very early lesions to partial colectomy for larger tumors—is the mainstay and may be curative, with adjuvant therapy considered based on pathology and risk features [5]. When metastases are limited, metastasectomy or liver‑directed interventions can offer long‑term control and even durable survival; specialized devices and HAI (hepatic artery infusion) are being revisited as options at high‑volume centers for selected patients [6] [3].
2. Standard cytotoxic chemotherapy: FOLFOX, FOLFIRI and the chemotherapy backbone
Systemic chemotherapy remains a core treatment for stage III and many stage IV cases, typically using oxaliplatin‑ or irinotecan‑based regimens such as FOLFOX or FOLFIRI; choice of backbone influences side‑effect profiles and is frequently paired with targeted agents in advanced disease [1] [5]. In metastatic settings chemotherapy often controls disease and is combined with other modalities when feasible, but oncologists stratify intensity by patient fitness and molecular features [5].
3. Targeted therapy for biomarker‑defined tumors: BRAF, VEGF and emerging agents
Targeted combinations are changing care for genetically defined subgroups: the BREAKWATER/BRAFTOVI data show encorafenib (BRAFTOVI) plus cetuximab added to FOLFIRI produced higher objective response rates versus FOLFIRI ± bevacizumab in BRAF V600E‑mutant mCRC—supporting this regimen as a potential new standard for that subset [1] [7]. Anti‑VEGF therapy (bevacizumab) is also used in combinations and remains part of triplet strategies tested with immunotherapy in trials [2].
4. Immunotherapy: effective for dMMR/MSI‑H, evolving for the majority
Immune checkpoint inhibitors have shown clear superiority as first‑line therapy for deficient mismatch repair (dMMR)/MSI‑H metastatic colorectal cancer, but monotherapy leaves a substantial minority who progress early (KEYNOTE‑177 context cited); the Phase 3 COMMIT trial found that combining chemotherapy and bevacizumab with atezolizumab markedly extended progression‑free survival versus atezolizumab alone in dMMR/MSI‑H mCRC, positioning chemo‑immunotherapy combinations as a new option for this subgroup [2]. For the large majority of MSS (microsatellite stable) tumors that historically do not benefit from PD‑1/PD‑L1 monotherapy, novel combos—including BOT/BAL and targeted kinase plus checkpoint regimens like zanzalintinib + atezolizumab—are under investigation with promising signals but are not yet standard [4] [8].
5. Personalized care, molecular testing and clinical trials drive choice
Current practice emphasizes biomarker testing because results determine eligibility for targeted drugs and immunotherapy and influence trial enrollment; major centers and guidelines recommend routine mutation and mismatch‑repair testing for advanced disease [9]. Many promising options remain investigational—trial access at centers such as MSK or UCSD gives patients earlier access to vaccines, ADCs and novel combinations—while press releases from industry (Pfizer) and advocacy materials can highlight positive subgroup data but carry forward‑looking language and commercial interests that should be weighed against peer‑reviewed reports [7] [10] [6].
6. Gaps, tradeoffs and realistic expectations
Even with recent advances, metastatic colorectal cancer outcomes vary: some molecular subsets now have substantially better control with new combos, but many patients still rely on sequential chemotherapy with limited survival gains; toxicities, the need for specialized delivery (HAI) or trial eligibility, and unequal access to high‑volume centers constrain real‑world impact [2] [3]. Ongoing Phase II/III studies presented at ASCO GI 2026 and summarized in the ASCO press program underscore rapid change in options—but evidence maturity, broader applicability and long‑term survival benefits will require follow‑up and independent validation [11] [12].