CurrentUnitedHealthcarePolicy N/A

Lonsurf (trifluridine/tipiracil) prior authorization

Defines UnitedHealthcare pharmacy prior authorization and reauthorization criteria for Lonsurf (trifluridine/tipiracil) for metastatic colorectal and gastric/gastroesophageal junction adenocarcinoma, and special handling for patients under 19. Applies to UnitedHealthcare benefit plans where PA is required.

Policy Summary

PayerUnitedHealthcare

PolicyLonsurf (trifluridine/tipiracil) prior authorization

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateJul 1, 2025

Next Review DateApr 20, 2025

Key ActionObtain prior authorization and document prior therapies, contraindications, or intolerances; approvals are issued for 12 months.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 moauthorization duration

age <19pediatric auto-process

2indications covered

4/2025P&T review

Coverage Criteria for Lonsurf (trifluridine/tipiracil)

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Metastatic Colorectal Cancer — Initial Authorization

Covered when ALL of the following are met for metastatic colorectal cancer

mCRC diagnosis: Diagnosis of advanced or metastatic colorectal cancer (colon, appendiceal, or rectal)

Prior therapy requirements: History of failure, contraindication, or intolerance to treatment with all of the following: fluoropyrimidine-based chemotherapy; oxaliplatin-based chemotherapy; irinotecan-based chemotherapy; and anti-VEGF biological therapy

RAS status / anti-EGFR: Either tumor is RAS mutant-type OR (tumor is RAS wild-type AND history of failure, contraindication, or intolerance to anti-EGFR therapy)

Gastric/Gastroesophageal Junction Adenocarcinoma — Initial Authorization

Covered when ALL of the following are met for gastric/gastroesophageal junction adenocarcinoma

Diagnosis: Unresectable locally advanced, recurrent, or metastatic gastric cancer OR unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma

Prior therapy requirements: History of failure, contraindication, or intolerance to at least two prior lines of chemotherapy that included a fluoropyrimidine and a platinum agent, and a taxane or irinotecan; include HER2-targeted therapy if HER2 overexpression

For members under 19 years of age, prescriptions for Lonsurf (trifluridine/tipiracil) will automatically process without a coverage review. When such automatic processing occurs, an authorization will be issued for 12 months. Note that specific state mandates regarding off‑label coverage or required compendium references may supersede the benefit language and apply instead.

Provider Actions, Prior Authorization, and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Lonsurf (trifluridine/tipiracil) for members aged 19 and older. Typical initial and reauthorization approvals are issued for 12 months when criteria are met.

Prior authorization required for members ≥ 19 years
Typical authorization duration: 12 months

Denial Risk

Missing Prior Therapy Documentation May Lead to Denial

If required prior therapy trials, documented contraindications, or documented intolerance to specified chemotherapies or biologics are not included with the request, the authorization may be denied. Ensure the chart or prior-authorization submission clearly shows trials, dates, and reason for discontinuation (failure, contraindication, or intolerance).

Denial risk when prior therapy, contraindication, or intolerance documentation is missing
Include dates and reason for discontinuation for each prior therapy trial

Documentation Required

Required Clinical Documentation

Submit documentation that demonstrates the member meets all applicable clinical criteria for the indication requested. Include: diagnosis (cancer type and staging or description e.g., metastatic colorectal cancer or unresectable locally advanced gastric/gastroesophageal junction adenocarcinoma); detailed history of prior therapies attempted (agent names, line of therapy, start and stop dates); responses to prior therapies and reasons for discontinuation (progression, toxicity, contraindication, or intolerance); tumor molecular status when relevant (e.g., RAS mutation or RAS wild‑type and anti‑EGFR therapy history); and current clinical status showing lack of progressive disease for reauthorization.

Diagnosis with anatomic site and stage or extent of disease
List of prior systemic therapies with agent names and dates
For each prior therapy, document response and reason for discontinuation (failure/progression, intolerance, or contraindication)
Tumor molecular testing results when applicable (e.g., RAS status)
Clinical notes or imaging reports supporting no progressive disease for reauthorization requests

Initial Therapy Requirements

Initial therapy

Initial authorization requirements

Indication and prior therapy for mCRC: Diagnosis of advanced/metastatic colorectal cancer AND history of failure, contraindication, or intolerance to fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and anti-VEGF biological therapy; plus RAS-related anti-EGFR requirement as specified

Authorization will be issued for 12 months

Indication and prior therapy for gastric/GEJ: Diagnosis of unresectable locally advanced, recurrent, or metastatic gastric or gastroesophageal junction adenocarcinoma AND history of failure, contraindication, or intolerance to at least two prior chemotherapy lines including a fluoropyrimidine, a platinum agent, and a taxane or irinotecan; include HER2-targeted therapy if HER2 overexpression

Authorization will be issued for 12 months

Prior Therapy Trials / Step Therapy Requirements

Required prior agents/regimens	Documentation required
Fluoropyrimidine-based chemotherapy	Record of trial and either documented failure, contraindication, or intolerance to fluoropyrimidine-based therapy
Oxaliplatin-based chemotherapy	Record of trial and either documented failure, contraindication, or intolerance to oxaliplatin-based therapy
Irinotecan-based chemotherapy	Record of trial and either documented failure, contraindication, or intolerance to irinotecan-based therapy
Anti-VEGF biological therapy	Record of trial and either documented failure, contraindication, or intolerance to anti-VEGF therapy
RAS-directed requirement for mCRC: either RAS mutant OR (RAS wild-type plus anti‑EGFR trial)	Tumor RAS status and if RAS wild-type, documentation of trial and failure, contraindication, or intolerance to anti‑EGFR therapy
For gastric/GEJ cancer: at least two prior chemotherapy lines including fluoropyrimidine, a platinum agent, and a taxane or irinotecan; include HER2‑targeted therapy if HER2+	Records of the at least two prior lines naming agents used, with documentation of failure, contraindication, or intolerance; note HER2 testing and receipt of HER2‑targeted therapy if HER2 overexpression

Key Definitions

Lonsurf (trifluridine/tipiracil) — drug description, indication summary and age notes

Drug descriptionLonsurf (trifluridine/tipiracil) is an oral combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor.

Primary indications (adults)Metastatic colorectal cancer (as single agent or with bevacizumab) after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti‑VEGF biologic, and if RAS wild‑type, an anti‑EGFR therapy.

Additional indication (adults)Metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two lines of chemotherapy that included a fluoropyrimidine, a platinum agent, and either a taxane or irinotecan; include HER2‑targeted therapy if HER2 overexpression.

NCCN guidanceNCCN recognizes Lonsurf for second‑line and subsequent therapy for advanced/metastatic colon, appendiceal, or rectal cancer, alone or with bevacizumab (preferred).

Age notesIndicated and described in adults; separate pediatric processing: members under 19 years process without coverage review per policy rules (see coverage criteria).

Background and Clinical Pharmacology

Lonsurf (trifluridine/tipiracil) is an oral combination cytotoxic chemotherapy composed of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor. It is indicated for previously treated metastatic colorectal cancer and metastatic gastric/gastroesophageal junction adenocarcinoma and is recognized in compendia such as the NCCN for use in advanced colorectal malignancies.