Description
Cemiplimab-rwlc (Libtayo^®) is a recombinant human IgG4 monoclonal antibody that is indicated for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer. The primary treatment goal of CSCC is complete removal of the tumor with maximal preservation of function and cosmesis. Most patients affected by CSCC have localized disease which can be cured with surgery, although some patients may require adjuvant radiotherapy for tumors with aggressive features, positive surgical margins or operable, regional lymph node involvement.

However, in a small percentage of patients CSCC progresses to locally advanced or metastatic disease which is no longer treatable by surgery or radiation. These patients may be considered for palliative systemic therapy which may include cytotoxic agents or EGFR inhibitors, although the data supporting the efficacy of these treatment options are limited.

Cemiplimab-rwlc (Libtayo) is a human programmed death receptor-1 (PD-1) blocking antibody that was approved by the U.S. Food and Drug Administration (FDA) in September 2018 for the treatment of metastatic or locally advanced CSCC. It works by binding to PD-1 and blocking its interaction with PD-1 ligands 1 and 2 (PD-L1 and PD-L2), which is the interaction responsible for inhibition of T-cell proliferation and cytokine production; thus, releasing the PD-1 pathway-mediated inhibition of immune response, including anti-tumor response.

Policy 
Cemiplimab-rwlc (Libtayo) is considered MEDICALLY NECESSARY when the following criteria is met:

Initial Therapy

Cemiplimab-rwlc (Libtayo) is considered MEDICALLY NECESSARY for the treatment of adult patients (≥ 18 years old) with cutaneous squamous cell carcinoma (CSCC) when the following criteria are met:

• The patient has metastatic or locally advanced disease; and
• The patient is not a candidate for curative surgery or curative radiation

Cemiplimab-rwlc (Libtayo) is considered MEDICALLY NECESSARY for the treatment of Basal cell carcinoma, locally advanced or metastatic previously treated with a hedgehog pathway inhibitor or when a hedgehog pathway inhibitor is not appropriate.

Cemiplimab-rwlc (Libtayo) is considered MEDICALLY NECESSARY for the treatment of Non–small cell lung cancer, locally advanced or metastatic as first-line treatment in patients whose tumors have high PD-L1 expression (Tumor Proportion Score ≥ 50%) as determined by an approved test, with no EGFR, ALK, or ROS1 aberrations, and locally advanced (in patients who are not candidates for surgical resection or definitive chemoradiation) or metastatic disease.

Initial authorization: 6 months

Continuation Therapy
Continuation of treatment with cemiplimab-rwlc (Libtayo) beyond 6 months after initiation of therapy, and every 6 months thereafter, is considered MEDICALLY NECESSARY for the treatment of cutaneous squamous cell carcinoma (CSCC) when the following criteria are met:

• The patient has been receiving cemiplimab-rwlc treatment previously; and
• The patient has not had disease progression or unacceptable toxicity while receiving cemiplimab-rwlc.

Continuation of treatment with cemiplimab-rwlc (Libtayo) beyond 6 months after initiation of therapy, and every 6 months thereafter, is considered MEDICALLY NECESSARY for the treatment of basal cell carcinoma and NSCLC until disease progression.

Cemiplimab-rwlc (Libtayo) is considered investigational and/ or unproven and therefore NOT MEDICALLY NECESSARY when the above criteria are not met.

BlueCross BlueShield of South Carolinarecognizes uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals, and selected supportive therapies) to be MEDICALLY NECESSARY if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered investigation/unproven therefore NOT MEDICALLY NECESSARY.

Rationale
The efficacy of cemiplimab-rwlc (Libtayo) for the treatment of metastatic or locally advanced CSCC in patients who are not candidates for curative surgery or curative radiation was evaluated in two open-label, multicenter, non-randomized, multicohort studies, NCT02383212, a phase 1 study with 26 patients and NCT02760498, a phase 2 study with 82 patients.. Of the 108 patients, 33 had locally advanced disease and 75 had metastatic CSCC (69% with distant metastases and 31% only nodal metastases). Half of the patients had received at least one prior anti-cancer systemic therapy, 96% had received prior cancer-related surgery and 79% had received prior radiotherapy. The primary outcome was overall response rate (ORR), as measured by independent central review and/or Response Evaluation Criteria In Solid Tumors (RECIST). Patients received cemiplimab 3mg/kg intravenously every 2 weeks with response assessment every 8 weeks, for up to 48 weeks in the phase 1 trial and up to 96 weeks in the phase 2 trial. Treatment was given until disease progression, unacceptable toxicity or completion of planned treatment. The efficacy analysis was conducted after all patients had at least 6 months of followup. The ORR (95% confidence interval) for the 108 patients was 47.2% (37.5 – 57.1%). The partial response rate was 43.5% and complete response rate 3.7%. The duration of response ranged from 1 to 15+ months, with 61% of patients having a duration of response of ≥6 months. Adverse events in the phase 2 study included diarrhea, fatigue, nausea, constipation and rash; four patients (7%) discontinued treatment due to an adverse event.

References

1. Regeneron Pharmaceuticals, Inc. Libtayo (cemiplimab-rwlc) injection for intravenous use. Highlights of prescribing information. January 2019. Available at: https://www.regeneron.com/sites/default/files/Libtayo_FPI.pdf. Accessed February 2019.
2. U.S. Food and Drug Administration. FDA approves first treatment for advanced form of the second most common skin cancer. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622044.htm. Accessed February 2019.
3. Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med 2018;379(4):341-51. Available at: https://www.nejm.org/doi/pdf/10.1056/NEJMoa1805131. Accessed March 2019.
4. Falchook GS, Leidner R, Stankevich E, et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer 2016;4:70. Available at: https://jitc.biomedcentral.com/articles/10.1186/s40425-016-0176-3. Accessed March 2019.
5. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Squamous Cell Skin Cancer, version 2.2019. Revised October 23, 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed February 2019.
6. Medical Director review 9/2019 

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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