Date: December 8, 2025
Table of Contents
- Proposed Decision
- Background
- Evidence
- Evidence Questions
- Technology Assessments
- Medicare Evidence Development and Coverage Advisory Committee (MEDCAC)
- Clinical Literature Search
- Assessment of the Evidence
- Evidence-Based Guidelines
- Professional Society Recommendations / Consensus Statements / Other Expert Opinion
- Appropriate Use Criteria
- Public Comment
- CMS Coverage Analysis
- CMS Coverage Authority
- CMS Analysis and Rationale for Proposed Decision
- Benefit Category
- History of Medicare Coverage
- Current National Coverage Request
- Timeline of NCA Milestones
- Appendices
Appendix A: Proposed Medicare National Coverage Determinations Manual Language
Abbreviations used throughout the Proposed Decision Memorandum for Anti-Cancer Chemotherapy for Colorectal Cancer
CFR – Code of Federal Regulations
CMS – Centers for Medicare & Medicaid Services
CTP – Clinical Trial Policy
FDA – Food and Drug Administration
HCFA – Health Care Financing Administration
MAC – Medicare Administrative Contractor
MEDCAC – Medicare Evidence Development & Coverage Advisory Committee
NCD – National Coverage Determination
NCI – National Cancer Institute
US – United States
USC – United States Code
I. Proposed Decision
The Centers for Medicare & Medicaid Services (CMS) proposes to remove the national coverage determination (NCD) 110.17 for Anti-cancer Chemotherapy for Colorectal Cancer[1]. Removing this NCD would not end the opportunity for coverage for these agents. Other coverage mechanisms exist including the Clinical Trial Policy NCD 310.1[2] and, separately, off-label use of anti-cancer chemotherapeutic agents are coverable according to § 1861(t)(2)(B) of the Social Security Act (the Act)[3].
See Appendix A for proposed Medicare National Coverage Determinations Manual removal language.
CMS is seeking comments on our proposed decision. We will respond to public comments in a final decision memorandum, as required by § 1862(l)(3) of the Act.
II. Background
This section provides an explanation of policies relevant to NCD 110.17. The discussion facilitates an understanding of the procedural history of NCD 110.17 and currently available coverage mechanisms should NCD 110.17 be removed.
NCD 110.17 – Anti-Cancer Chemotherapy for Colorectal Cancer
On February 12, 2003, CMS initiated an NCD for oxaliplatin to examine appropriate use in the Medicare program. On May 2, 2003, after internal review and analysis of public comments, CMS decided to also add irinotecan to the NCD review. On September 1, 2004, CMS further modified the review to include consideration of off-label uses of oxaliplatin, irinotecan, cetuximab, and bevacizumab that were not listed as indicated in one or more of the major drug compendia cited in § 1861(t)(2)(B)(ii)(I) of the Act. On September 15, 2004, CMS and the National Cancer Institute (NCI) discussed aligning their resources to accelerate the development of evidence for emerging cancer treatment regimens. Following these discussions, on January 28, 2005, CMS posted the final decision memorandum[4] which finalized NCD 110.17 to cover off-label uses of oxaliplatin, irinotecan, cetuximab, and bevacizumab in colorectal and other cancer types in nine NCI-sponsored trials.
NCD 310.1 – Routine Costs in Clinical Trials (aka Clinical Trial Policy (CTP))
On September 19, 2000, the Health Care Financing Administration (HCFA) (now CMS) implemented the CTP through NCD 310.1 for Routine Costs in Clinical Trials. The CTP was developed in response to a June 7, 2000 Presidential Executive Memorandum concerning payment for costs incurred by Medicare beneficiaries participating in clinical trials. The NCD relied on the statutory authority of Section 1862(a)(1)(E) of the Act. The 2000 NCD limited Medicare payment to routine items and services provided to Medicare beneficiaries and only in qualified trials. In general, the policy defined “routine costs” as those items and services that would generally be covered for Medicare beneficiaries outside a trial.
In July 2006, CMS reconsidered the 2000 NCD; convened a Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) to obtain public input and recommendations; asked the Agency for Healthcare Research and Quality to provide recommended changes; and received public comments on the proposed decision. The resulting final NCD, effective July 9, 2007, modified language from the 2000 NCD that had been interpreted by some stakeholders to restrict payment for investigational items or services. The final NCD clarified that investigational items or services are covered under the CTP if they are coverable outside of the clinical research trial[5].
Sections 1861(b) Inpatient Hospital Services and (s) Medical and Other Health Services
Under § 1861(b) of the Act, anti-cancer chemotherapeutics, such as oxaliplatin, irinotecan, cetuximab, and bevacizumab, are covered as a Part A benefit when administered in an inpatient hospital setting. Under § 1861(s)(2)(A), these agents are covered as a Part A benefit when administered in a physician’s office or outpatient setting, provided that the Medicare Administrative Contractors (MACs) determine that agents are not usually self-administered. Similarly, under § 1861(s)(2)(B), coverage extends to administration in an outpatient hospital setting when MACs determine the agents are not usually self-administered.
Section 1861(t)(2) Drugs and Biologicals
Under § 1861(t)(2)(B) of the Act, reimbursement is available for off-label uses of Food and Drug Administration (FDA) approved drugs and biologicals used in an anti-cancer chemotherapeutic regimen under specific circumstances:
(A) For purposes of paragraph (1), the term "drugs" also includes any drugs or biologicals used in an anticancer chemotherapeutic regimen for a medically accepted indication (as described in subparagraph (B)).
(B) In subparagraph (A), the term "medically accepted indication", with respect to the use of a drug, includes any use which has been approved by the Food and Drug Administration for the drug, and includes another use of the drug if—
(i) the drug has been approved by the Food and Drug Administration; and
(ii)(I) such use is supported by one or more citations which are included (or approved for inclusion) in one or more of the following compendia: the American Hospital Formulary Service-Drug Information, the American Medical Association Drug Evaluations, the United States Pharmacopoeia-Drug Information (or its successor publications), and other authoritative compendia as identified by the Secretary, unless the Secretary has determined that the use is not medically appropriate or the use is identified as not indicated in one or more such compendia, or
(II) the carrier involved determines, based upon guidance provided by the Secretary to carriers for determining accepted uses of drugs, that such use is medically accepted based on supportive clinical evidence in peer reviewed medical literature appearing in publications which have been identified for purposes of this subclause by the Secretary.
The Secretary may revise the list of compendia in clause (ii)(I) as is appropriate for identifying medically accepted indications for drugs. On and after January 1, 2010, no compendia may be included on the list of compendia under this subparagraph unless the compendia has a publicly transparent process for evaluating therapies and for identifying potential conflicts of interests. (42 U.S.C. § 1395x(t)(2)[6]).
Effective January 1, 1994, the HCFA (now CMS) implemented a change in policy in response to the addition of § 1861(t)(2). HCFA published contractor guidance in the Carriers Manual, part 3, section 2049 (now the Medicare Benefit Policy Manual, chapter 15, section 50[7]) for unlabeled indications of FDA approved drugs and biologicals used in anti-cancer chemotherapeutic regimens for medically accepted indications.
Also effective January 1, 1994, by authority of § 1861(s)(2)(Q), HCFA extended coverage under specified conditions to prescribed oral anti-cancer drugs that are versions of covered non-self-administrable chemotherapeutic agents. The oral drug must have the same active ingredients as the covered non-self-administrable anti-cancer drug or biological that it replaces, must be furnished incident to a physician’s service, and must be used for the same indications (including unlabeled uses) as the drug it replaces. Effective January 1, 1999, CMS expanded coverage of oral anti-cancer drugs to include FDA-approved prodrugs used to replace the covered non-self-administrable version of the drug. A prodrug may have a different chemical composition than the non-self-administrable version of the drug it replaces but metabolizes into the same chemical composition in the body.
III. Evidence
CMS did not develop evidence questions or perform an evidence review on the aforementioned drugs or other anti-cancer chemotherapeutic agents. Rather, we focus on other available Medicare policies that are redundant to NCD 110.17. Importantly, all clinical trials approved by CMS under this NCD have either ended or have reached primary completion as of 2025. We believe future trials could be coverable under the mechanisms described previously (NCD 310.1 and §§ 1861 (b), (s), and (t)(2) of the Act).
B. Technology Assessments
CMS did not request an external technology assessment on this topic.
C. Medicare Evidence Development and Coverage Advisory Committee (MEDCAC)
A MEDCAC meeting was not convened on this topic.
D. Clinical Literature Search
As noted above, CMS did not perform an evidence review for this NCD analysis.
E. Assessment of the Evidence
CMS did not assess evidence for this NCD analysis.
F. Evidence-Based Guidelines
CMS did not search for or review evidence-based guidelines.
G. Professional Society Recommendations / Consensus Statements / Other Expert Opinion
CMS did not search for or review professional society recommendations, consensus statements or other expert opinion.
H. Appropriate Use Criteria
CMS did not search for or review appropriate use criteria.
Because CMS opened this NCD analysis with a proposed decision memorandum, there will be one 30-day public comment period which commences with the posting of this proposed decision memorandum. Public comments that cite published clinical evidence give CMS useful information. Public comments that contain information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination.
IV. CMS Coverage Analysis
A. CMS Coverage Authority
National coverage determinations (NCDs) are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally by Medicare (§ 1869(f)(1)(B) of the Act). In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B and must not be otherwise excluded from coverage. Moreover, with limited exceptions, items or services must be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member (§ 1862(a)(1)(A) of the Act).
Additionally, as described above, § 1861(t)(2)(B) of the Act specifies the coverage provisions for off-label uses of FDA approved drugs and biologicals used in an anti-cancer chemotherapeutic regimen. Separate from this authority, coverage is also available in clinical trials under the CTP NCD 310.1.
B. CMS Analysis and Rationale for Proposed Decision
The Centers for Medicare & Medicaid Services proposes to remove the NCD 110.17. Removing this NCD does not end the opportunity for coverage. Other existing coverage mechanisms remain available including the CTP (NCD 310.1) and, separately, off-label use of anti-cancer chemotherapeutic agents are coverable pursuant to § 1861(t)(2)(B) of the Act. The NCD CMS proposes for removal was established in 2005. In 2007, CMS updated the CTP NCD 310.1. The CTP updates included clear language stating that investigational items or services would be covered under the CTP if they are coverable outside of the clinical research trial. According to their records on clinicaltrials.gov (identified by the study numbers in the list of CMS identified trials: https://www.cms.gov/determinationprocess/downloads/id90b.pdf), all of the studies covered under NCD 110.17 are complete or terminated, with the exception of one study that remains active, but is no longer recruiting and had a primary completion date in early 2025 and an estimated study completion date in early 2026. Since the studies approved under this NCD have all ended or reached primary completion, and the drugs covered under NCD 110.17 are coverable under the CTP NCD 310.1 and/or § 1861(t)(2)(B) of the Act if supported by evidence or included in a covered compendia, we propose to remove NCD 110.17 to eliminate redundancy and better streamline the NCD policies and manual.
For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in § 1812 (Scope of Part A); § 1832 (Scope of Part B); or § 1861(s) (Definition of Medical and Other Health Services) of the Act.
Anti-Cancer Chemotherapy for Colorectal Cancer qualifies as:
- Social Security Act § 1861(t)(2)(B)
Note: This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service.
V. History of Medicare Coverage
A. Current National Coverage Request
CMS internally generated the opening of this NCD reconsideration to review the status of the related CMS approved studies, other existing coverage mechanisms available for investigational items under the CTP NCD 310.1 and, separately, under § 1861(t)(2)(B) of the Act.
B. Timeline of NCA Milestones
| Date |
Milestone |
| December 8, 2025 |
CMS posts a tracking sheet announcing the opening of the NCA reconsideration and simultaneously posts the proposed decision memorandum. The 30-day public comment period begins.
|
VI. Appendices
Appendix A: Proposed Medicare National Coverage Determinations Manual Language
110.17 - Anti-Cancer Chemotherapy for Colorectal Cancer (RETIRED)
Effective XXXX, the Centers for Medicare & Medicaid Services (CMS) removed NCD 110.17, ending coverage of the off-label use of clinical items and services, including the use of the studied drugs oxaliplatin, irinotecan, cetuximab, or bevacizumab, in specific clinical trials identified by CMS.
