RXMP-34 Oncology Medication Clinical Review Guideline Form

Oncology Medication Clinical Review Guideline

Updated on: 9/11/2025

Page 1 of 4 Policy Number RXMP-34 Line of Business Medicaid & Medicare Effective Date 1/1/2026 Revision Date 9/11/2025 Description This guideline provides parameters for coverage of injectable oncology medication (including, but not limited to octreotide acetate, leuprolide acetate, leucovorin, and levoleucovorin), including therapeutic radiopharmaceuticals, covered under the medical benefit based upon the National Cancer Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendia® (NCCN Compendia®). The Compendium lists the appropriate drugs and biologics for specific cancers using the US Food and Drug Administration (FDA) approved disease indications and specific NCCN panel recommendations. Each recommendation is supported by a level of evidence category. Coverage of White Blood Cell Colony Stimulating Factors, Erythropoiesis Stimulating Agents, Bone Modifying Agents, Antiemetics for Chemotherapy and Hormonal Therapy are addressed in separate guidelines. This policy does not provide coverage criteria for Chimeric Antigen Receptor (CAR T)-Cell products. Coverage determinations are based on the member’s benefits and the transplant solutions criteria for covered transplants. Considerations

1. Chemotherapy, Immunotherapy and Hormonal Agents Chemotherapy, immunotherapy, and hormonal agents are covered when medically indicated and used according to FDA approved indications or as a part of an anticancer chemotherapeutic regimen or cancer treatment regimen. FDA approved drug or biological is one that has received final marketing approval by the Food and Drug Administration (FDA) and, as a part of its labeling, contains its recommended uses and dosages as well as adverse reactions and recommended precautions in using it.

2. Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen Off-label, medically accepted indications of Food and Drug Administration (FDA) approved drugs and biologicals used in an anti-cancer chemotherapeutic regimen are identified under the conditions described below. A regimen is a combination of anti-cancer agents clinically recognized for the treatment of a specific type of cancer. Off-label, medically accepted indications are supported in either one or more of the compendia or in peer-reviewed medical literature. Compendia documentation or peer-reviewed literature supporting off-label use by the treating physician may also be requested.

3. Compendia List AlohaCare and its delegates do not deny coverage based solely on the absence of FDA-approved labeling for the use, if the use is supported by any of the following compendia and the use is not listed as unsupported, not indicated, not recommended, or equivalent terms, in any of the following compendia:
   • American Hospital Formulary Service-Drug Information (AHFS-DI) (Existing)
   • National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium (Effective June 5, 2008).
   • Micromedex DrugDex (Effective June 10, 2008)
   • Clinical Pharmacology (Effective July 2, 2008)
   • Lexi-Drugs (Effective August 12, 2015)

   The listed compendia employ various rating and recommendation systems that may not be readily cross walked from compendium to compendium. In general, a use is identified by a compendium as medically accepted if the: • Indication is a category 3 in NCCN or class III in DrugDex; or • Narrative text in AHFS or Clinical Pharmacology is “not supportive”; or • Indication is listed in Lexi-Drugs as “Use: Unsupported”.

   The complete absence of narrative test on a use is considered neither supportive nor non-supportive.

Oncology Medication Clinical Review Guideline

Updated on: 9/11/2025

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4. Use Supported by Clinical Research that Appears in Peer-Reviewed Medical Literature Peer-reviewed medical literature may appear in scientific, medical, and pharmaceutical publications in which original manuscripts are published, only after having been critically reviewed for scientific accuracy, validity, and reliability by unbiased, independent experts prior to publication. In-house publications of entities whose business relates to the manufacture, sale, or distribution of pharmaceutical products are excluded from consideration. Abstracts (including meeting abstracts) are excluded from consideration. In determining whether an off-label use is supported, evaluate the evidence in published, peer-reviewed medical literature listed below. When evaluating this literature, consider (among other things) the following: • Whether the clinical characteristics of the patient and the cancer are adequately represented in the published evidence
   • Whether the administered chemotherapy regimen is adequately represented in the published evidence
   • Whether the reported study outcomes represent clinically meaningful outcomes experienced by patients
   • Whether the study is appropriate to address the clinical question, consider: o Whether the experimental design, considering the drugs and conditions under investigation, is appropriate to address the investigative question (for example, in some clinical studies, it may be unnecessary or not feasible to use randomization, double blind trials, placebos, or crossover) o That non-randomized clinical trials with a significant number of subjects may be a basis for supportive clinical evidence for determining accepted uses of drugs; and, o That case reports are generally considered uncontrolled and anecdotal information and do not provide adequate supportive clinical evidence for determining accepted uses of drugs.

   Use peer-reviewed medical literature appearing in the regular editions of the following publications, not to include supplement editions privately funded by parties with a vested interest in the recommendations of the authors: • American Journal of Medicine;
   • Annals of Internal Medicine; • Annals of Oncology;
   • Annals of Surgical Oncology;
   • Biology of Blood and Marrow Transplantation;
   • Blood;
   • Bone Marrow Transplantation;
   • British Journal of Cancer;
   • British Journal of Hematology;
   • British Medical Journal; Cancer;
   • Clinical Cancer Research; Drugs;
   • European Journal of Cancer (formerly the European Journal of Cancer and Clinical Oncology);
   • Gynecologic Oncology;
   • International Journal of Radiation, Oncology, Biology, and Physics;
   • The Journal of the American Medical Association;
   • Journal of Clinical Oncology;
   • Journal of the National Cancer Institute;
   • Journal of the National Comprehensive Cancer Network (NCCN);
   • Journal of Urology;
   • Lancet;
   • Lancet Oncology;
   • Leukemia;
   • The New England Journal of Medicine; or
   • Radiation Oncology.

Oncology Medication Clinical Review Guideline

Updated on: 9/11/2025

Page 3 of 4 Notes: • FDA approved drugs and biologicals may also be considered for use in the determination of medically accepted indications for off-label use if to be reasonable and necessary. • If a use is identified as not indicated by the Centers for Medicare and Medicaid Services (CMS) or the FDA, or if a use is specifically identified as not indicated in one or more of the compendia listed, or it’s determined, based on peer- reviewed medical literature, that a particular use of a drug is not safe and effective, the off-label usage is not supported and, therefore, the drug is not covered. (This criterion does not apply for the determination of drug eligibility for Part D.)

5. NCCN Categories of Evidence and Consensus The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are comprehensive guidelines documenting management decisions and interventions that apply to 97% of cancers affecting U.S. patients. • Category 1: The recommendation is based on high-level evidence (i.e., high-powered randomized clinical trials or meta-analyses), and the panel has reached uniform consensus that the recommendation is indicated. In this context, uniform means near unanimous positive support with some possible neutral positions. • Category 2A: The recommendation is based on lower-level evidence, but despite the absence of higher-level studies, there is uniform consensus that the recommendation is appropriate. Lower-level evidence is interpreted broadly and runs the gamut from phase II to large cohort studies to case series to individual practitioner experience. Importantly, in many instances, the retrospective studies are derived from clinical experience of treating large numbers of patients at a member institution, so panel members have first-hand knowledge of the data. Inevitably, some recommendations must address clinical situations for which limited, or no data exist. In these instances, the congruence of experience-based opinions provides an informed if not confirmed direction for optimizing patient care. These recommendations carry the implicit recognition that they may be superseded as higher-level evidence becomes available or as outcomes-based information becomes more prevalent. • Category 2B: The recommendation is based on lower-level evidence, and there is nonuniform consensus that the recommendation should be made. In these instances, because the evidence is not conclusive, institutions take different approaches to the management of a particular clinical scenario. This nonuniform consensus does not represent a major disagreement, rather it recognizes that given imperfect information, institutions may adopt different approaches. A Category 2B designation should signal to the user that more than one approach can be inferred from the existing data. • Category 3: The recommendation has engendered a major disagreement among the panel members. Several circumstances can cause major disagreements. For example, if substantial data exists about two interventions but they have never been directly compared in a randomized trial, adherents to one set of data may not accept the interpretation of the other side's results. Another situation resulting in a Category 3 designation is when experts disagree about how trial data can be generalized. A Category 3 designation alerts users to a major interpretation issue in the data and directs them to the manuscript for an explanation of the controversy.

   This medical guideline aids in interpreting National Comprehensive Cancer Network (NCCN)® cancer guidelines. Before using this guideline, please check the member specific benefit plan documents and any applicable federal or state mandates. AlohaCare and its delegates reserves the right to modify its Guidelines as necessary. This Guideline is provided for informational purposes and does not constitute medical advice.

   This guideline may also be applied to Medicare Advantage plans in some instances. In the absence of a Medicare National Coverage Determination (NCD), Local Coverage Determination (LCD), or other Medicare coverage guidance, CMS allows a Medicare Advantage Organization (MAO) to create its own coverage determinations, using objective evidence-based rationale relying on authoritative evidence. (Medicare IOM Pub. No. 100-16, Chapter 4, Section 90.5)

   AlohaCare’s Medical Benefit Guidelines are intended to be used in connection with the independent professional medical judgement of a qualified health care provider and do not constitute the practice of medicine or medical advice.

Oncology Medication Clinical Review Guideline

Updated on: 9/11/2025

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6. Examples of Not Reasonable and Necessary Determinations as to whether medication is reasonable and necessary for an individual patient should be made on the same basis as all other such determinations (i.e., with the advice of medical consultants and with reference to accepted standards of medical practice and the medical circumstances of the individual case). The following guidelines identify three categories with specific examples of situations in which medications would not be reasonable and necessary according to accepted standards of medical practice: • Not for Particular Illness: Medications given for a purpose other than the treatment of a particular condition, illness, or injury are not covered (except for certain immunizations). Charges for medications, e.g., vitamins, given simply for the general good and welfare of the patient and not as accepted therapies for a particular illness are excluded from coverage. • Injection Method Not Indicated: Medication given by injection (parenterally) is not covered if standard medical practice indicates that the administration of the medication by mouth (orally) is effective and is an accepted or preferred method of administration. For example, the accepted standard of medical practice for the treatment of certain diseases is to initiate therapy with parenteral penicillin and to complete therapy with oral penicillin. AlohaCare and its delegates exclude the entire charge for penicillin injections given after the initiation of therapy if oral penicillin is indicated unless there are special medical circumstances that justify additional injections. • Excessive Medications: Medications administered for treatment of a disease, and which exceed the frequency or duration of injections indicated by accepted standards of medical practice are not covered. For example, the accepted standard of medical practice in the maintenance treatment of pernicious anemia is one vitamin B-12 injection per month. AlohaCare and its delegates exclude the entire charge for injections given more than this frequency unless there are special medical circumstances that justify additional injections.

   Notes:
   • AlohaCare and its delegates will supplement the guidelines as necessary with guidelines concerning appropriate use of specific injections in other situations. They will use the guidelines to screen out questionable cases for special review, further development, or denial when the injection billed for would not be reasonable and necessary. They will coordinate any type of drug treatment review with the Quality Improvement Organization (QIO).
   • If a medication is determined not to be reasonable and necessary for diagnosis or treatment of an illness or injury according to these guidelines, AlohaCare excludes the entire charge (i.e., for both the drug and its administration). Also, AlohaCare excludes from payment any charges for other services (such as office visits) which were primarily for the purpose of administering a non-covered injection (i.e., an injection that is not reasonable and necessary for the diagnosis or treatment of an illness or injury).

   Review History: Updated on: 9/11/2025