CurrentCignaPolicy N/A

Oncology - Lonsurf Prior Authorization Policy

Defines prior authorization requirements for coverage of Lonsurf (trifluridine and tipiracil) under Cigna-administered health benefit plans for indicated metastatic colorectal and gastric/gastroesophageal junction cancers.

Policy Summary

PayerCigna

PolicyOncology - Lonsurf Prior Authorization Policy

Policy CodePolicy N/A

Change TypeMaterial and operational updates

Effective Date

Next Review DateFeb 7, 2024

Key ActionObtain prior authorization and document prior chemotherapy exposure (fluoropyrimidine, oxaliplatin, irinotecan) and any required biomarker-directed therapies to qualify for coverage.

SourceLink

POLICY UPDATE CHANGES

Appendiceal was added to the condition of approval for colon/rectal cancer.

Examples of fluoropyrimidines and examples of chemotherapy regimens were moved into a Note.

2FDA-approved indications described

1 yearTypical approval duration

NCCN citedCompendia/guideline references

Coverage Criteria for Lonsurf (trifluridine and tipiracil)

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Colon/Rectal/Appendiceal cancer (metastatic)

A) Patient has been previously treated with a fluoropyrimidine.
Examples of fluoropyrimidines include capecitabine and 5‑fluorouracil (5‑FU).
B) Patient has been previously treated with oxaliplatin.
C) Patient has been previously treated with irinotecan.
D) If the patient’s tumor or metastases are RAS wild‑type (KRAS and NRAS mutation negative), the patient has tried cetuximab (Erbitux) or panitumumab (Vectibix).

Gastric or gastroesophageal junction adenocarcinoma (metastatic): Approve for 1 year if the patient has been previously treated with at least two chemotherapy regimens for gastric or gastroesophageal junction adenocarcinoma.1 year approval

Example chemotherapy regimen agents include capecitabine, 5‑fluorouracil (5‑FU), oxaliplatin, paclitaxel, docetaxel, and irinotecan.

Regimen	Indication	Coverage
Lonsurf (trifluridine and tipiracil) alone
Colorectal (colon, rectal, or appendiceal) cancer: subsequent (third-line or later) therapy for advanced or metastatic disease not previously treated with Lonsurf
Covered when FDA‑approved criteria are met (prior fluoropyrimidine, oxaliplatin, irinotecan; if RAS wild‑type, prior cetuximab or panitumumab). Approvals provided for 1 year.

Regimen	Indication	Coverage
Lonsurf (trifluridine and tipiracil) as single agent
Gastric or gastroesophageal junction (GEJ) adenocarcinoma: third‑line or subsequent therapy for unresectable locally advanced, recurrent, or metastatic disease (Karnofsky ≥60% or ECOG ≤2)
Covered when patient has been previously treated with at least two chemotherapy regimens for gastric/GEJ adenocarcinoma. Approval provided for 1 year.

Provider Requirements and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization Required: Prior authorization is recommended for prescription benefit coverage of Lonsurf. Approvals are provided for one year when criteria are met.

Lonsurf (trifluridine and tipiracil) — prior authorization recommended; approvals granted for 1 year when criteria are met.

Step Therapy

Required Prior Therapies

Required prior therapies: Coverage requires prior exposure to specific chemotherapies. For colon, rectal, or appendiceal cancer, all of the following must be documented: previous treatment with a fluoropyrimidine (examples: capecitabine, 5‑fluorouracil), oxaliplatin, and irinotecan. Additionally, if the tumor/metastases are wild‑type RAS (KRAS and NRAS wild‑type), prior trial of EGFR therapy (cetuximab or panitumumab) is required. For gastric or gastroesophageal junction adenocarcinoma, the patient must have been previously treated with at least two chemotherapy regimens for that disease. Example chemotherapy agents/regimens include capecitabine, 5‑fluorouracil (5‑FU), oxaliplatin, paclitaxel, docetaxel, and irinotecan.

Colon/rectal/appendiceal cancer: prior fluoropyrimidine, oxaliplatin, irinotecan; plus prior cetuximab or panitumumab if tumor is RAS wild‑type.
Gastric/gastroesophageal junction adenocarcinoma: prior treatment with at least two chemotherapy regimens.
Example agents/regimens: capecitabine, 5‑FU, oxaliplatin, paclitaxel, docetaxel, irinotecan.

Documentation Required

Required Prior Treatment Documentation

Required prior treatment documentation: Document the patient’s prior treatment history demonstrating receipt of the specified prior chemotherapies and regimens relevant to the indication. For colorectal/appendiceal disease, include dates and agents showing prior use of a fluoropyrimidine, oxaliplatin, and irinotecan; document RAS mutation status (KRAS and NRAS) and, if RAS wild‑type, prior receipt of cetuximab or panitumumab. For gastric/gastroesophageal junction adenocarcinoma, document prior receipt of at least two chemotherapy regimens for that disease, including regimen names, agents, and treatment dates. Include clinic notes, infusion records, or discharge summaries as supporting evidence.

Provide documentation of agents and dates for prior fluoropyrimidine, oxaliplatin, and irinotecan.
Document KRAS and NRAS mutation status; if wild‑type, document prior cetuximab or panitumumab therapy.
For gastric/GEJ adenocarcinoma, document at least two prior chemotherapy regimens with agents and dates.
Acceptable supporting records: clinic notes, infusion records, discharge summaries.

Denial Risk

Experimental/Unproven Uses

Experimental/Unproven Uses: Lonsurf is considered experimental, investigational, or unproven for any indication other than the FDA‑approved indications and the uses described in this policy.

Use of Lonsurf for indications other than those listed as FDA‑approved (colon/rectal/appendiceal cancer; gastric/GEJ adenocarcinoma per criteria) is experimental/investigational/unproven.

Intended Line of Therapy / Salvage Use

salvage

NCCN/guideline placement for Lonsurf.

Subsequent/third‑line or later therapy: Lonsurf is positioned as subsequent (third‑line or later) or salvage therapy for advanced/metastatic colorectal and gastric/gastroesophageal junction cancers per guideline recommendations.

Biomarker and Molecular Testing Requirements

RAS (KRAS and NRAS) — required status (inv-11)

Required biomarker statusRAS (KRAS and NRAS) wild-type — tumors/metastases must be KRAS and NRAS mutation negative

Action when RAS wild-typeIf RAS wild-type, prior trial of anti‑EGFR therapy (cetuximab or panitumumab) is required before approval

ApplicabilityRequirement applies to colon, rectal, or appendiceal metastatic disease per FDA‑approved indication

HER2 — testing/requirement (inv-12)

HER2 testing considerationFor gastric/GEJ adenocarcinoma, HER2-targeted therapy should be given if appropriate prior to Lonsurf (document HER2 status and prior HER2-directed therapy when applicable)

DocumentationIf HER2-targeted therapy was appropriate, provider should document prior receipt of HER2/neu-targeted therapy

Source guidanceHER2 guidance referenced in FDA indication and NCCN gastric cancer guideline

Definitions and Clinical Criteria

trifluridine and tipiracil tablets; combination of a nucleoside metabolic inhibitor and a thymidine phosphorylase inhibitor (inv-08)

Generic descriptiontrifluridine and tipiracil tablets — a combination of a nucleoside metabolic inhibitor (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil)

Brand nameLonsurf (trifluridine and tipiracil tablets)

Indications summaryOral combination indicated for metastatic colorectal and metastatic gastric/GEJ adenocarcinoma after prior lines of therapy

Karnofsky ≥ 60% or ECOG ≤ 2 — performance status (inv-09)

Performance requirementKarnofsky performance score ≥ 60% OR ECOG performance status ≤ 2 (as referenced in guideline recommendations)

Context of useReferenced in NCCN gastric and esophagogastric junction guideline recommendations for third‑line or subsequent therapy

PopulationApplies to patients considered for Lonsurf as subsequent/third‑line therapy for gastric/GEJ locoregional or metastatic disease

Permitted Regimens and Combinations

Regimen	Indication	Coverage
Lonsurf (trifluridine and tipiracil) alone or Lonsurf plus bevacizumab
Colorectal (colon, rectal, or appendiceal) cancer: subsequent (third-line or later) therapy for advanced or metastatic disease not previously treated with Lonsurf
Covered when FDA‑approved criteria are met (prior fluoropyrimidine, oxaliplatin, irinotecan; if RAS wild‑type, prior cetuximab or panitumumab). Approvals provided for 1 year.

Regimen	Indication	Coverage
Lonsurf (trifluridine and tipiracil) as single agent
Gastric or gastroesophageal junction (GEJ) adenocarcinoma: third‑line or subsequent therapy for unresectable locally advanced, recurrent, or metastatic disease (Karnofsky ≥60% or ECOG ≤2)
Covered when patient has been previously treated with at least two chemotherapy regimens for gastric/GEJ adenocarcinoma. Approval provided for 1 year.

Background

Lonsurf is an oral combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor. It is indicated for certain patients with metastatic colorectal cancer (colon, rectal, and appendiceal sites) and metastatic gastric/gastroesophageal junction adenocarcinoma after prior lines of therapy and is recommended by guidelines as a subsequent (third‑line or later) option; use may be as a single agent or, in colorectal cancer, in combination with bevacizumab in appropriate settings.

Revision History

2024-02-07Annual reviewLatest

Policy reviewed (Annual Revision) with editorial changes moving examples of fluoropyrimidines and chemotherapy regimens into a Note; no change to clinical coverage intent.

2023-02-15Annual revision - material change

Appendiceal was added to the condition of approval for colon/rectal cancer (expanded labeled anatomical sites).