CMS NCD 291 Modified: Anti-Cancer Chemotherapy Coverage for Colorectal Cancer (2026)

CMS has modified National Coverage Determination (NCD) 291, which governs Medicare coverage of anti-cancer chemotherapy agents used in colorectal cancer treatment. This update—effective March 12, 2026—clarifies coverage rules for four key drugs: oxaliplatin (Eloxatin™), irinotecan (Camptosar®), cetuximab (Erbitux™), and bevacizumab (Avastin™). If your practice or facility bills Medicare for colorectal cancer chemotherapy, this policy directly affects how you document and submit claims.

What NCD 291 Covers: CMS Colorectal Cancer Drug Coverage Framework

The Centers for Medicare & Medicaid Services structures coverage for these four colorectal cancer chemotherapy agents across three distinct pathways. Understanding which pathway applies to each patient encounter is essential for clean claims submission.

Pathway 1 — FDA-Approved Indications: Oxaliplatin, irinotecan, cetuximab, and bevacizumab are covered when used in accordance with their FDA-approved labeling. This is the most straightforward coverage pathway and typically carries the lowest documentation burden.

Pathway 2 — Compendium-Supported Off-Label Use: Off-label use is covered when the indication is supported by one of the authoritative drug compendia listed in Section 1861(t)(2)(B)(ii)(I) of the Social Security Act. If you're billing for an off-label indication, your documentation must reflect the specific compendium reference supporting that use.

Pathway 3 — MAC Discretionary Coverage: Medicare Administrative Contractors (MACs) retain authority to determine coverage for off-label uses not covered under Pathways 1 or 2, based on guidance provided by the Secretary under Section 1861(t)(2)(B)(ii)(II) of the Act. This pathway requires the most robust medical necessity documentation and is subject to variation by MAC jurisdiction.

CMS Coverage of Off-Label Use in NCI-Sponsored Clinical Trials

One of the most significant components of NCD 291 is its Coverage with Evidence Development (CED) provision. CMS covers the off-label use of oxaliplatin, irinotecan, cetuximab, and bevacizumab when patients are enrolled in specific clinical trials identified by CMS—all of which are sponsored by the National Cancer Institute (NCI).

These NCI-sponsored trials study one or more off-label uses of these four drugs in colorectal cancer and in other cancer types. The full list of CMS-identified trials is maintained on the CMS website and accessible via the CED page for off-label use of colorectal cancer drugs.

This is a critical distinction for billing teams: if a patient is receiving an off-label chemotherapy regimen outside of an identified trial, coverage defaults to the compendium or MAC pathways—not the CED pathway. Misclassifying the coverage basis is a common source of claim denials and audit exposure.

Routine Clinical Trial Costs: What NCD 291 Does and Doesn't Change

NCD 291 explicitly states that it does not alter Medicare's existing coverage framework for routine costs in clinical trials under NCD Manual Section 310.1. Routine costs continue to be covered for the identified NCI trials, as do other items and services provided as a result of coverage under this policy.

The basic requirements for enrollment in a covered trial remain unchanged. This means your clinical trial billing protocols—coordination with research teams, condition codes, clinical trial-specific claim requirements—should remain intact. NCD 291 is not a vehicle to expand clinical trial billing beyond the identified CMS trial list.

What Hasn't Changed Under NCD 291

This modification does not alter coverage requirements for FDA-approved indications or compendium-listed indications for any of the four drugs. MACs retain their authority to make reasonable and necessary coverage determinations for medically accepted off-label uses provided outside of identified clinical trials.

In plain terms: existing coverage for standard-of-care regimens is preserved. The modification does not restrict what was previously covered, nor does it require you to re-establish medical necessity for established treatment protocols already billed under FDA-approved or compendium-supported indications.

Benefit Category: Incident to Billing Implications

NCD 291 falls under the benefit category of "incident to a physician's professional service." This has direct implications for how chemotherapy administration claims are structured when the drugs are administered in a physician office or clinic setting.

Under incident-to rules, the service must be rendered under the direct supervision of the billing physician, and the physician must be present in the office suite. For hospital outpatient settings, different billing rules apply—outpatient chemotherapy administration is billed under the facility's outpatient prospective payment rules. Make sure your billing team is applying the correct benefit category context based on the site of service.

Affected Codes

The policy data for NCD 291 does not list specific CPT or HCPCS drug administration or drug supply codes. The four chemotherapy agents are referenced by name and brand name only within the policy text.

Drug Agents Referenced in Policy (No Code Assignments Listed):

Because the policy does not specify HCPCS J-codes, CPT administration codes, or ICD-10-CM diagnosis codes, billing teams should reference their MAC's local coverage articles and the applicable HCPCS Level II codebook for the correct drug codes (e.g., J9055 for cetuximab, J9035 for bevacizumab) and verify those codes remain consistent with the MAC's published guidance for this NCD.

What Your Billing Team Should Do