Commercial

Medical Policy

Notification

Pemetrexed (Pemfexy™)

Notification Issue Date:

This version of the policy will become effective 11/07/2022.

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia for Nonsquamous Non-Small Cell Lung Cancer (NSCLC) and Ovarian cancer, Fallopian Tube Cancer, and Peritoneal Cancer, including the additional indication of Malignant Peritoneal Mesothelioma (Sarcomatoid, Epithelioid, Biphasic, Benign Multicystic, Well-Differentiated Papillary) and Low-Grade Serous Carcinoma.

The following ICD-10 codes have been added to this policy:

C45.2 Mesothelioma of pericardium
C45.7 Mesothelioma of other sites
C45.9 Mesothelioma, unspecified

The following ICD-10 codes have been removed from this policy:

C34.00 Malignant neoplasm of unspecified main bronchus
C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung
C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung
C56.9 Malignant neoplasm of unspecified ovary
C57.00 Malignant neoplasm of unspecified fallopian tube
C57.10 Malignant neoplasm of unspecified broad ligament
C57.20 Malignant neoplasm of unspecified round ligament
D15.0 Benign neoplasm of thymus

Title:

Pemetrexed (Pemfexy™)

Policy #:

08.00.87p

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

INDEX OF MEDICALLY NECESSARY INDICATIONS

This policy addresses numerous medically necessary indications for the use of pemetrexed (Pemfexy) listed in order of appearance within the Policy section. Please see below for the specific medical necessity criteria. (NOTE: Experimental/Investigational section below must also be reviewed).

Type of cancer	Subtype of cancer
Central Nervous System Cancers	Leptomeningeal Metastases Primary Central Nervous System Lymphoma Limited Brain Metastases Extensive Brain Metastases
Cervical Cancer
Malignant Pleural Mesothelioma Malignant Peritoneal Mesothelioma	Sarcomatoid, Epithelioid, Biphasic
Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (e.g., Adenocarcinoma with Mixed Subtypes)	Large Cell Carcinoma, Locally Advanced or Metastatic
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancers	Epithelial Ovarian Cancer, Fallopian Tube Cancer, Carcinosarcoma (Malignant Mixed Müllerian Tumors), Clear Cell Carcinoma of the Ovary, Mucinous Carcinoma of the Ovary, Grade 1 Endometrioid Carcinoma, Low-Grade Serous Carcinoma, Primary Peritoneal Cancer
Thymic Carcinoma and Thymoma
Thyroid Carcinoma	Papillary Carcinoma
Vaginal Cancer

MEDICALLY NECESSARY

Pemetrexed (Pemfexy) is considered medically necessary and, therefore, covered for the following conditions:

CENTRAL NERVOUS SYSTEM CANCERS

Primary Central Nervous System Lymphoma

Induction therapy as a single agent if individual who is unsuitable for or intolerant to high-dose methotrexate for one of the following indications:

Primary CNS lymphoma (PCNSL)
Primary vitreoretinal lymphoma/PCNSL ocular variant (without other CNS involvement)

For the treatment of individuals as a single-agent treatment for relapsed or refractory disease, for any of the following indications:

Prior whole-brain radiation therapy (RT)
Prior high-dose methotrexate-based regimen without prior RT
With whole-brain RT or involved-field RT in individuals who received a prior high-dose methotrexate-based regimen, without prior RT after no response or short response duration (12 months or more) to the prior regimen
Prior high-dose systemic therapy with stem cell rescue

Limited Brain Metastases

Used for limited brain metastases in non-small cell lung cancer (NSCLC) in combination with amivantamab-vmjw and carboplatin for exon 19 deletion or L858R (National Comprehensive Cancer Network [NCCN] preferred regimen) or in combination with osimertinib and cisplatin or carboplatin for one of the following indications:

As initial treatment in select cases (e.g., small asymptomatic brain metastases) for newly diagnosed or stable systemic disease or if reasonable systemic treatment options exist
As treatment for recurrent brain metastases

Extensive Brain Metastases

Used for extensive brain metastases in NSCLC in combination with amivantamab-vmjw and carboplatin for exon 19 deletion or L858R (NCCN preferred) or in combination with osimertinib and cisplatin or carboplatin for one of the following:

May be considered as primary treatment in select cases (e.g., small asymptomatic brain metastases)
As treatment for recurrent disease with stable systemic disease or reasonable systemic treatment options

Leptomeningeal Metastases

For the treatment of individuals with intracerebrospinal fluid (CSF) leptomeningeal metastases from NSCLC that is EGFR mutation-positive for one of the following indications:

As primary treatment in individuals with good risk status (Karnofsky Performance Status [KPS] ≥60, no major neurologic deficits, minimal systemic disease, and reasonable systemic treatment options if needed)
As maintenance treatment in individuals with negative CSF cytology or in clinically stable individuals with persistently positive CSF cytology

MESOTHELIOMA

Peritoneal

Used in combination with cisplatin or carboplatin (both NCCN preferred for epithelioid histology), or as a single agent as first-line systemic therapy for*^% any of the following indications:

Adjuvant treatment of medically operable and complete cytoreduction achievable; with preoperative low-risk features^{^}following cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC), if presence of any surgical/pathologic high-risk features^‡
Medically operable disease and complete cytoreduction achievable; with preoperative low risk features^{^} if progression following CRS + HIPEC if no prior adjuvant systemic therapy given
Medically inoperable disease; complete cytoreduction not achievable, or presence of any high-risk features^‡

Used in combination with one of the following regimens:

Pembrolizumab and (cisplatin or carboplatin) (NCCN preferred)
Bevacizumab and (cisplatin or carboplatin) (NCCN preferred for epithelioid histology)

The above regimens are used as first-line systemic therapy for*^%any of the following:

Adjuvant treatment of medically operable and complete cytoreduction achievable; with preoperative low-risk features^{^} following CRS + HIPEC, if presence of any surgical/pathologic high-risk features^‡
Medically operable disease and complete cytoreduction achievable; with preoperative low risk features^{^}if progression following CRS + HIPEC if no prior adjuvant systemic therapy given
Medically inoperable disease; complete cytoreduction not achievable, or presence of any high-risk features^‡

NCCN notes: *May also be used for pericardial mesothelioma and tunica vaginalis testis mesothelioma.
^% Best supportive care is recommended for individuals presenting with PS 3–4.
^{^}Low-risk features: epithelioid histology; absence of any high-risk features.
^‡High-risk features: biphasic/sarcomatoid histology, nodal metastasis, Ki-67 >9%, thrombocytosis, PS 2, bicavitary disease, high disease burden/incomplete cytoreduction (Peritoneal Cancer Index [PCI] >17, completeness of cytoreduction [cc] score >1)

Subsequent systemic therapy*^{%^} as a single agent (NCCN preferred)
NCCN preferred subsequent systemic therapy*%, if immunotherapy was administered as first-line treatment or to be considered as a rechallenge if good response to front-line pemetrexed (Pemfexy)–based treatment with one of the following regimens:

In combination with cisplatin
In combination with cisplatin and bevacizumab
In combination with carboplatin
In combination with carboplatin and bevacizumab

NCCN notes: *May also be used for pericardial mesothelioma and tunica vaginalis testis mesothelioma.
^%Best supportive care is recommended for individuals presenting with PS 3–4.

^Consider rechallenge with pemetrexed-based therapy if good response to front-line pemetrexed-based treatment.

Pleural

Induction systemic therapy*^{^} for clinical stage I disease and epithelioid histology prior to surgical exploration and one of the following regimens:

In combination with cisplatin or carboplatin (NCCN preferred)
In combination with (cisplatin or carboplatin) and pembrolizumab (NCCN preferred)
In combination with (cisplatin or carboplatin) and bevacizumab (NCCN preferred)
As a single agent

Used in combination with cisplatin or carboplatin (both NCCN preferred for epithelioid histology) as first-line systemic therapy*^{^} for one of the following stages:

Clinical stage I disease and epithelioid histology as initial treatment
Clinical stage II-IV disease and epithelioid histology, sarcomatoid or biphasic histology (any stage), or if medically inoperable as initial treatment
Clinical stage I disease and epithelioid histology following surgical exploration (if induction systemic therapy not given)

Single-agent therapy as first-line systemic therapy*^{^} for one of the following stages:

Clinical stage I disease and epithelioid histology as initial treatment
Clinical stage II-IV disease and epithelioid histology, sarcomatoid or biphasic histology (any stage), or if medically inoperable as initial treatment
Clinical stage I disease and epithelioid histology following surgical exploration (if induction systemic therapy not given)

Used in combination with one of the following regimens:

(Cisplatin or carboplatin) and pembrolizumab (NCCN preferred)
(Cisplatin or carboplatin) and bevacizumab (NCCN preferred for epithelioid histology)

The above regimens are used as first-line systemic therapy*^{^} for for one of the following indications:

Clinical stage I disease and epithelioid histology as initial treatment
Clinical stage II–IV disease and epithelioid histology, sarcomatoid or biphasic histology (any stage), or if medically inoperable as initial treatment
Clinical stage I disease and epithelioid histology following surgical exploration (if induction systemic therapy not given)

Subsequent systemic therapy as a single agent (NCCN preferred)
As the initial treatment of malignant pleural mesothelioma in individuals with unresectable disease or who are otherwise not candidates for curative surgery in combination with cisplatin
NCCN-preferred subsequent systemic therapy, if immunotherapy was administered as first-line treatment or to be considered as a rechallenge if good response to front-line pemetrexed (Pemfexy)–based treatment and one of the following regimens:

In combination with cisplatin
In combination with cisplatin and bevacizumab
In combination with carboplatin
In combination with carboplatin and bevacizumab

NCCN notes: *May also be used for pericardial mesothelioma and tunica vaginalis testis mesothelioma.

^{^}Best supportive care is recommended for individuals presenting with PS 3–4.

NONSQUAMOUS NSCLC (e.g., ADENOCARCINOMA WITH MIXED SUBTYPES), LARGE CELL CARCINOMA
Pemetrexed (Pemfexy) are indicated for the treatment of individuals with nonsquamous NSCLC for the following indications:

Preoperative Therapy

For the treatment of individuals as preoperative concurrent chemoradiation (NCCN-preferred regimen) in combination with carboplatin or cisplatin, for any of the following indications:

Superior sulcus tumors (T3 invasion, N0-1)
Possibly resectable superior sulcus tumors (T4 invasion, N0-1)
Chest wall, trachea/carina, or mediastinum; T3 invasion, N0-1; resectable T4 invasion, N0-1 disease
Resectable stage IIIA (T4 [size], N0-1) disease

Neoadjuvant Therapy

As neoadjuvant systemic therapy in combination with cisplatin (NCCN preferred) or carboplatin (useful in certain circumstances for those who are not candidates for cisplatin-based therapy) if tumor deemed resectable after surgical evaluation and if likely to receive adjuvant chemotherapy for stage IB or IIA (if high-risk features are present)*, or stage IIB, IIIA or IIIB ([T2-T3, N2b; T4, N2]) if ineligible for immunotherapy or targeted therapy.

NCCN note: *Examples of high-risk features may include poorly differentiated tumors (including lung neuroendocrine tumors [excluding well-differentiated neuroendocrine tumors]), vascular invasion, wedge resection, visceral pleural involvement, and unknown lymph node status (Nx).

Neoadjuvant systemic therapy for stage IB–IIIA, IIIB (T2–T3, N2b; T4, N2) disease (tumors ≥4 cm or node positive) for nonsquamous histology if tumor deemed resectable after surgical evaluation (if candidates for immune checkpoint inhibitors)* in combination with one of the following regimens:

cisplatin and nivolumab (if no known EGFR mutations or ALK gene fusion)
carboplatin and nivolumab (if no known EGFR mutations or ALK gene fusion)
cisplatin and pembrolizumab
cisplatin or carboplatin and durvalumab (if no known EGFR mutations or ALK gene fusion)

NCCN note: *Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, and some oncogenic drivers (i.e., EGFR exon 19 deletion or L858R mutation; ALK, RET, or ROS1 gene fusion) have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors.

As neoadjuvant systemic therapy for nonsquamous histology in combination with osimertinib and either cisplatin or carboplatin for stage II-IIIA, IIIB ([T2–T3, N2b; T4, N2]) NSCLC that is positive for EGFR exon 19 deletion or L858R mutation if tumor deemed resectable after surgical evaluation

As neoadjuvant systemic therapy for stage IB–IIIA, IIIB (T2–T3, N2b; T4, N2) disease (tumors ≥4 cm or node positive) for nonsquamous histology if tumor deemed resectable after surgical evaluation (if candidates for immune checkpoint inhibitors)* in combination with one of the following regimens:

Cisplatin and nivolumab (if no known EGFR mutations or ALK rearrangements)
Carboplatin and nivolumab (if no known EGFR mutations or ALK rearrangements)
Cisplatin and pembrolizumab
Cisplatin or carboplatin and durvalumab (and no known EGFR mutations or ALK rearrangements)

NCCN note: *Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, and some oncogenic drivers (i.e., EGFR exon 19 deletion or exon 21 L858R, ALK rearrangements) have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors.

Initial Treatment

As NCCN-preferred concurrent chemoradiation in combination with carboplatin or cisplatin as a consideration if stereotactic ablative radiotherapy (SABR) is not feasible as initial treatment for those who are medically inoperable, high surgical risk as determined by thoracic surgeon and those who decline surgery after thoracic surgical consultation and any of the following indications:

Stage IB (peripheral T2a, N0), stage I (central T1–T2a, N0), stage II (T1–T2ab, N1; T2b, N0), stage IIB (T1, N2a; T3, N0), or stage IIIA (T3, N1) on clinical assessment that is N0 after pathologic lymph node evaluation
T2a-3, N0 disease on mediastinal biopsy

For the treatment of individuals as initial treatment, for any of the following regimens:

In combination with pembrolizumab and platinum chemotherapy for metastatic disease with no EGFR or ALK genomic tumor aberrations
In combination with cisplatin for locally advanced or metastatic disease
As a single agent for the maintenance treatment of individuals with locally advanced or metastatic, nonsquamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
As a single agent for the treatment of individuals with recurrent, metastatic nonsquamous, NSCLC after prior chemotherapy.

For the treatment of individuals as initial (NCCN-preferred regimen) definitive concurrent chemoradiation (in combination with carboplatin or cisplatin) for any of the following indications:
- Medically inoperable high surgical risk as determined by thoracic surgeon, and those who decline surgery after thoracic consultation for T1-3, N1 nodes positive, M0 disease on mediastinal biopsy
- Unresectable superior sulcus tumors (T4 invasion, N0-1)
- Unresectable stage IIIA (T4, N0-1)
- T1-T3, N2 nodes positive, M0 disease on mediastinal biopsy
- Stage IIIB (T1-2, N3) and stage IIIC (T3, N3) (following pathologic confirmation of N3 disease)
- Contralateral or ipsilateral mediastinal node-positive stage IIIB (T4, N2) and stage IIIC (T4, N3) (following pathologic confirmation of N2-3 disease)
- Stage IVA, M1b and stage IVB (T1-3, N1-2 or T4, N0-2) disease if performance status 0–2 and solitary or limited non-brain metastases confirmed, if definitive therapy for thoracic disease is feasible

Treatment for Recurrent, Advanced, or Metastatic Disease

For the treatment of individuals as first-line therapy for one of the following:

As first-line therapy for EGFR exon 19 deletion or exon 21 L858R recurrent, advanced, or metastatic disease in combination with osimertinib and cisplatin or carboplatin.
NCCN-preferred first-line therapy for EGFR exon 20 insertion mutation positive recurrent, advanced, or metastatic disease in combination with amivantamab-vmjw and carboplatin.

For the treatment of individuals as first-line therapy for PD-L1 expression–positive (≥1%) tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
and no contraindications** to PD-1 or PD-L1 inhibitors, and PS 0-2 for any of the following regimens:

In combination with pembrolizumab and either carboplatin or cisplatin (NCCN-preferred regimen)
In combination with nivolumab, ipilimumab, and either carboplatin or cisplatin
in combination with cemiplimab-rwlc and either carboplatin or cisplatin (NCCN preferred)

Treatment for recurrent, advanced, or metastatic disease of nonsquamous cell histology, for individuals with performance status 0-2, no contraindications** to PD-1 or PD-L1 inhibitors, and no EGFR exon 19 deletion or L858R; ALK, RET, or ROS1 gene fusion in combination with any of the following:
- Either cisplatin or carboplatin and pembrolizumab (NCCN preferred)
- Nivolumab, ipilimumab, and either carboplatin or cisplatin
- Cemiplimab-rwlc and either carboplatin or cisplatin (NCCN preferred)
- Tremelimumab-actl, durvalumab, and either carboplatin or cisplatin
NCCN notes: *Complete genotyping for EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, NRG1, and ERBB2 (HER2), via biopsy and/or plasma testing. Treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes.
**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, and some oncogenic drivers (i.e., EGFR exon 19 deletion or exon 21 L858R; ALK, RET, or ROS1 rearrangements) have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors.

Treatment for recurrent, advanced, or metastatic disease of nonsquamous cell histology if contraindications** to PD-1 or PD-L1 inhibitors or if EGFR exon 19 deletion or L858R mutation; ALK, RET, or ROS1 gene fusion and performance status 0–2

In combination with carboplatin or cisplatin if contraindications** to PD-1 or PD-L1 inhibitors for PS 0–1 or NCCN preferred for PS 2
As a single agent

The above regimens are used as one of the following lines of therapy:

Initial systemic therapy for PD-L1 expression positive (≥1%) and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive) with contraindications to PD-1 or PD-L1 inhibitors
Initial systemic therapy for PD-L1 <1% and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
First-line therapy for EGFR exon 20 mutation–positive tumors
First-line or subsequent therapy for BRAF V600E mutation–positive tumors
First-line or subsequent therapy for NTRK1/2/3 gene fusion–positive tumors
First-line or subsequent therapy for MET exon 14 skipping mutation–positive tumors
Subsequent therapy for RET rearrangement–positive tumors and prior pralsetinib, selpercatinib, or cabozantinib
First-line or subsequent therapy therapy for ERBB2 (HER2) mutation–positive tumors
First-line therapy for NRG1 gene fusion positive tumors
Subsequent therapy for EGFR exon 19 deletion or exon 21 L858R tumors and prior erlotinib ± (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, amivantamab-vmjw + lazertinib or dacomitinib therapy
Subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation–positive tumors and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy
Subsequent therapy for ALK rearrangement–positive tumors and prior crizotinib, ceritinib, alectinib, brigatinib, ensartinib or lorlatinib therapy
Subsequent therapy for ROS1 rearrangement–positive tumors and prior crizotinib, entrectinib, repotrectinib, or taletrectinib, or lorlatinib therapy
Subsequent therapy for PD-L1 expression–positive (≥1%) tumors and negative for actionable molecular biomarkers* after prior PD-1/PD-L1 inhibitor but no prior platinum-containing chemotherapy

For the treatment of individuals with recurrent, advanced, or metastatic disease, with PS 0–1 and no history of recent hemoptysis if contraindications** to PD-1 or PD-L1 inhibitors or if EGFR exon 19 deletion or L858R mutation; ALK, RET, or ROS1 gene fusion in combination with one of the following regimens and lines of therapy:

In combination with one of the following regimens:

Bevacizumab and cisplatin
Bevacizumab and carboplatin

For any of the following lines of therapy:

Initial systemic therapy for PD-L1 <1% and negative for actionable molecular biomarkers^* (may be KRAS G12C mutation positive) with contraindications to PD-1 or PD-L1 inhibitors
Initial systemic therapy for PD-L1 <1% and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
First-line therapy for EGFR exon 20 mutation–positive tumors
First-line or subsequent therapy for BRAF V600E mutation–positive tumors
First-line or subsequent therapy for NTRK1/2/3 gene fusion–positive tumors
First-line or subsequent therapy for MET exon 14 skipping mutation–positive tumors
First-line therapy for ERBB2 (HER2) mutation–positive tumors
First-line therapy for NRG1 gene fusion positive tumors
Subsequent therapy for RET rearrangement–positive tumors and prior pralsetinib, selpercatinib, or cabozantinib
Subsequent therapy for EGFR mutation–positive (exon 19 deletion or exon 21 L858R) tumors and prior erlotinib ± (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, amivantamab-vmjw + lazertinib, or dacomitinib therapy
Subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation–positive tumors and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy
Subsequent therapy for ALK rearrangement–positive tumors and prior alectinib, brigatinib, ceritinib, crizotinib, ensartinib, or lorlatinib therapy
Subsequent therapy for ROS1 rearrangement–positive tumors and prior crizotinib, entrectinib, repotrectinib taletrectinib, or lorlatinib therapy
Subsequent therapy for PD-L1 expression–positive (≥1%) tumors and negative for actionable molecular biomarkers* after prior PD-1/PD-L1 inhibitor but no prior platinum-containing chemotherapy

For the treatment of individuals with recurrent, advanced, or metastatic disease, with PS 0–2 and who achieve tumor response or stable disease following initial systemic therapy, for PD-L1 ≥50% in combination with durvalumab, for any of the following lines of therapy:

As a single agent for continuation maintenance therapy
In combination with bevacizumab for continuation maintenance therapy if bevacizumab previously used with a first-line pemetrexed (Pemfexy)/platinum chemotherapy regimen
In combination with pembrolizumab for continuation maintenance therapy if previously used first-line as part of a pembrolizumab/pemetrexed (Pemfexy) and either cisplatin or carboplatin regimen
In combination with cemiplimab-rwlc for continuation maintenance therapy if previously used as first-line as part of cemiplimab/pemetrexed (Pemfexy) and either cisplatin or carboplatin
As a single agent for switch maintenance

For the treatment of individuals as a single agent (if not already given) as subsequent systemic therapy for recurrent, advanced, or metastatic disease in individuals with an ECOG PS 0–2 and tumors, except for progression after subsequent systemic therapy and for locoregional recurrence or symptomatic local disease, except for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior RT) with no evidence of disseminated disease.
Continuation maintenance therapy in combination with pembrolizumab for recurrent, advanced, or metastatic disease for PD-L1 expression–positive (≥1%) or PD-L1 expression <1% tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive) and no contraindications** to PD-1 or PD-L1 inhibitors in individuals with PS 0–2 who achieve a response or stable disease following first-line therapy with pembrolizumab/pemetrexed and either cisplatin or carboplatin for nonsquamous cell histology

NCCN note: *Complete genotyping for EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, and ERBB2 (HER2), via biopsy and/or plasma testing. If a clinically actionable marker is found, it is reasonable to start therapy based on the identified marker. Treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes.

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene drivers (e.g., EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK , RET or ROS1 rearrangements), have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors.

Single agent (if not already given) as subsequent systemic therapy for recurrent, advanced, or metastatic disease in those with PS 0–2 and tumors of nonsquamous cell histology
NCCN-preferred subsequent therapy for EGFR exon 19 deletion or L858R mutation* positive recurrent, advanced, or metastatic disease (nonsquamous) in combination with amivantamab-vmjw (if not previously given) and carboplatin following disease progression on osimertinib or lazertinib for symptomatic systemic disease with multiple lesions

NCCN note: *not an option for EGFR S768I, L861Q, and/or G719X mutations

Concurrent Chemoradiation Therapy

For the treatment of individuals in combination with carboplatin or cisplatin if radiation not previously given for the treatment of locoregional recurrence or symptomatic local disease, for one of the following indications:
- Mediastinal lymph nodes
- Superior vena cava (SVC) obstruction

Adjuvant Chemotherapy

Adjuvant chemotherapy* in combination with cisplatin (NCCN preferred) or carboplatin (for those who are not candidates for cisplatin-based therapy) following resection based on findings at surgery for any of the following indications:

stage IB (for T2a tumors = 4cm, N0) with high risk features**
stage IIA (T2b, N0) with high risk features**
stage IIB (T1 2a, T2a-T2b N1; T3, N0;
stage IIIA (T1, N2b; T2, N2a; T3, N1-N2a; T4, N0–1) and stage IIIB (T2–T3, N2b; T4, N2)

NCCN-preferred adjuvant concurrent chemoradiation for nonsquamous cell histology in combination with carboplatin or cisplatin for margin-positive (R1 or R2) and any of the following indications:

stage IIB (T1, N2a; T2a–T2b, N1; T3, N0) based on findings at surgery
stage IIIA (T1, N2b;T2,N2a; T3, N1–N2a; T4, N0–1) and stage IIIB (T2–T3, N2b; T4, N2) based on findings at surgery
clinical presentation of disease in the chest wall, trachea/carina, mediastinum, or diaphragm; T3 invasion, N0–1; resectable T4 invasion, N0–1 following initial treatment with surgery
clinical presentation of stage IIIA (T4 [size], N0–1) disease following initial treatment with surgery

Adjuvant sequential chemoradiation for nonsquamous cell histology in combination with cisplatin (NCCN preferred) or carboplatin, for those who are not candidates for cisplatin-based therapy) for any of the following indications:

R1 or R2 stage IB (T2a, N0) (based on findings at surgery)
R1 or R2 stage IIA (T2b, N0) (based on findings at surgery)
R1 stage IIB (T1, N2a; T2a-T2b, N1; T3, N0) (based on findings at surgery)
R0 or R1 stage IIIA (T1, N2b; T2,N2a; T3, N1-N2a; T4, N0-1) and stage IIIB (T2-T3, N2b; T4, N2) (based on findings at surgery)
clinical presentation of disease in the chest wall, trachea/carina, mediastinum, or diaphragm; T3 or T4 invasion, N0-1; with R1 resection following initial treatment with surgery
clinical presentation of stage IIIA (T4 [size], N0-1) disease with R1 resection following initial treatment with surgery

NCCN note: *If received chemotherapy as part of neoadjuvant therapy, then adjuvant chemotherapy should not be given.

**Examples of high-risk features may include poorly differentiated tumors (including lung neuroendocrine tumors [excluding well-differentiated neuroendocrine tumors]), vascular invasion, wedge resection, visceral pleural involvement, and unknown lymph node status (Nx). These factors independently may not be an indication and may be considered when determining treatment with adjuvant chemotherapy.

OVARIAN CANCER, FALLOPIAN TUBE CANCER, PRIMARY PERITONEAL CANCER

Epithelial Ovarian Cancer, Fallopian Tube Cancer, Clear Cell Carcinoma of the Ovary, Mucinous Carcinoma of the Ovary, Grade 1 Endometrioid Carcinoma, Primary Peritoneal Cancer- Carcinoma (Malignant Mixed Müllerian Tumors)

For the treatment of individuals as a single-agent therapy for any of the following indications:

As immediate treatment for serially rising CA-125 in individuals who previously received chemotherapy

For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
For complete remission and relapse more than 6 months after completing chemotherapy (platinum-resistant disease)
For radiographic and/or clinical relapse in individuals with previous complete remission and relapse after 6 or more months after completing prior chemotherapy (platinum-sensitive disease)

Low-Grade Serous Carcinoma

For the treatment of individuals with a single-agent therapy of platinum-sensitive or platinum-resistant recurrence.

CERVICAL CANCER

As second-line or subsequent therapy as a single agent for the treatment of individuals with one of the following indications:

Local/regional recurrence
Stage IVB or recurrence with distant metastases

THYMOMAS AND THYMIC CARCINOMA

As preoperative systemic therapy for surgically resectable disease if R0 resection is considered uncertain as a single agent for those who cannot tolerate first-line combination regimens
For postoperative systemic therapy as a single agent for those who cannot tolerate first-line combination regimens for one of the following indications:
- Thymic carcinoma after R1 or R2 resection
- Thymoma after R2 resection

For the treatment of individuals as first-line therapy for recurrent, advanced, or metastatic disease as a single agent for those who cannot tolerate first-line combination regimens for any of the following:

Potentially resectable locally advanced disease
Potentially resectable solitary metastasis or ipsilateral pleural metastasis
Following surgery for solitary metastasis or ipsilateral pleural metastasis
Medically inoperable/unresectable solitary metastasis or ipsilateral pleural metastasis
Extrathoracic metastatic disease

Subsequent systemic therapy as a single agent (NCCN preferred for thymoma; other recommended therapy for thymic carcinoma) for one of the following indications:

Unresectable locally advanced disease

Solitary metastasis or ipsilateral pleural metastasis

Extrathoracic metastatic disease

THYROID CARCINOMA

Papillary Carcinoma, Follicular Carcinoma

For treatment in combination with carboplatin for progressive and/or symptomatic disease after progression following prior treatment, for one of the following:

Unresectable locoregional recurrent or persistent radioactive iodine (RAI)-refractory disease

Distant metastatic RAI-refractory disease

Oncocytic Carcinoma

If disease progression following prior treatment for treatment in combination with carboplatin of progressive and/or symptomatic for one of the following indications:

Unresectable locoregional recurrent or persistent disease

Distant metastatic disease

Anaplastic Carcinoma

In combination with carboplatin if disease progression following prior treatment as second-line therapy for stage IVC (metastatic) disease

VAGINAL CANCER

Second-line or subsequent therapy as a single agent for one of the following indications:

Locoregional recurrence
Stage IVB or recurrent distant metastases

EXPERIMENTAL/INVESTIGATIONAL

All other uses of pemetrexed (Pemfexy) are considered experimental/investigational and, therefore, are not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

MANDATES

PENNSYLVANIA MEMBERS

In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

SIDE EFFECTS/PHARMACOKINETICS

Individuals undergoing treatment with pemetrexed (Pemfexy) should be pretreated with folic acid, vitamin B₁₂, and dexamethasone to reduce the severity of hematologic and gastrointestinal toxicity of pemetrexed (Pemfexy). The vitamin therapy should continue on a daily basis as a prophylactic measure to reduce treatment-related hematologic toxicity.

Pemetrexed (Pemfexy) is primarily excreted unchanged by the kidney. Decreased renal function will result in reduced clearance and greater exposure area under curve (AUC) to pemetrexed (Pemfexy) compared to individuals with normal renal function. Hepatic and renal function should be monitored with periodic testing.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern US to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.

ECOG Performance Status
Grade	ECOG
0	Fully active, able to carry on all predisease performance without restriction
1	Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2	Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours
3	Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4	Completely disabled. Cannot carry on any self- care: totally confined to bed or chair
5	Dead

*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, pemetrexed (Pemfexy) intravenous (IV) infusion is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION STATUS (FDA)

Pemetrexed (Pemfexy) IV infusion was first approved by the FDA on February 8, 2020, in combination with cisplatin for the initial treatment of individuals with locally advanced or metastatic non-squamous, non-small cell lung cancer (NSCLC), as a single agent for the maintenance treatment of individuals with locally advanced or metastatic non-squamous NSCLC. Supplemental approvals for pemetrexed (Pemfexy) have since been issued by the FDA.

SQUAMOUS NON-SMALL CELL LUNG CANCER

Pemetrexed (Pemfexy) is not indicated for the treatment of individuals with squamous cell NSCLC.

Description

Pemetrexed (Pemfexy) for intravenous infusion is classified as an antineoplastic agent for use in chemotherapy as a single agent or in combination with other chemotherapy drugs. Pemetrexed (Pemfexy) is a folate analogue metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that pemetrexed inhibits TS, DHFR, and GARFT, which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers, such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT.

On December 13, 2019, Eagle Pharmaceuticals, Inc. and Eli Lilly and Company reached a settlement that allowed the US Food and Drug Administration (FDA) to shift the approval from tentative to final. The FDA approved Eagle Pharmaceuticals' pemetrexed (Pemfexy), calling it a branded alternative to Eli Lilly's Alimta®. The December announcement allowed for an initial limited entry of Pemfexy into the market on February 1, 2022, with an uncapped entry on April 1, 2022. The lawsuits were regarding patents.

The efficacy of pemetrexed (Pemfexy) was evaluated in Study JMDB (NCT00087711), a multicenter, randomized, open-label study conducted in 1725 chemotherapy-naive individuals with stage IIIb/IV NSCLC. Individuals were randomly assigned to receive pemetrexed with cisplatin or gemcitabine with cisplatin. Randomization was stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 versus 1, sex, disease stage, basis for pathological diagnosis (histopathological/cytopathological), history of brain metastases, and investigative center. Pemetrexed was administered intravenously over 10 minutes at a dose of 500 mg/m² on Day 1 of each 21-day cycle and cisplatin was administered intravenously at a dose of 75 mg/m² approximately 30 minutes after pemetrexed administration on Day 1 of each cycle. Gemcitabine was administered at a dose of 1250 mg/m² on Day 1 and Day 8 of each 21-day cycle and cisplatin was administered intravenously at a dose of 75 mg/m² approximately 30 minutes after administration of gemcitabine on Day 1 of each cycle. Treatment was administered up to a total of six cycles; individuals in both arms received folic acid, vitamin B₁₂, and dexamethasone. The major efficacy outcome measure was overall survival. A total of 1725 individuals were enrolled, with 862 individuals randomly assigned to pemetrexed in combination with cisplatin and 863 individuals to gemcitabine in combination with cisplatin. The median age was 61 years (range, 26–83 years), 70% were male, 78% were White, 17% were Asian, 2.9% were Hispanic or Latino, and 2.1% were Black or African American, and fewer than 1% were other races. Among individuals for whom ECOG PS (n=1722) and smoking history (n=1516) were collected, 65% had an ECOG PS of 1, 36% had an ECOG PS of 0, and 84% were smokers. For tumor characteristics, 73% had nonsquamous non-small cell lung cancer (NSCLC) and 27% had squamous NSCLC; 76% had stage IV disease. Among 1252 individuals with non-squamous NSCLC histology, 68% had a diagnosis of adenocarcinoma, 12% had large cell histology, and 20% had other histologic subtypes.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Cancer Society (ACS). What Is Non-Small Cell Lung Cancer? [ACS Web site]. 01/29/2024. Available at: What Is Lung Cancer? | Types of Lung Cancer | American Cancer Society. Accessed April 14, 2026.

Asukai Y, Valladares A, Camps C, et al. Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population. BMC Cancer. 2010;10:26.

Azzoli C, Temin S, Aliff T. 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice guideline update on chemotherapy for stage IV non-small-cell-lung cancer. J Clin Oncol. 2012;8(1):63-66.

Barlesi F, Scherpereel A. Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous non-small-cell lung cancer: update survival analysis of the AVAPERL (MO22089) randomized phase III trial. Ann Oncol. 2014;25:1044-1052.

Elsevier's Clinical Pharmacology Compendium. Pemetrexed (Pemfexy). [Clinical Key Web site]. 01/09/2026. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed April 14, 2026.

Lexi-Drugs Compendium. Pemetrexed. [Lexicomp Online Web site]. 04/16/2026. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed April 17, 2026.

Lorusso D, Ferrandina G, Pignata S, et al. Evaluation of pemetrexed (Alimta, LY231514) as second-line chemotherapy in persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group. Ann Oncol. 2009;21(1):61-66.

Malempati S, Nicholson H, Reid J, et al. Phase I trial and pharmacokinetic study of pemetrexed in children with refractory solid tumors: The Children's Oncology Group. J Clin Oncol. 2007;25(12):1505-1511.

Micromedex® Healthcare Series [Internet database]. Pemetrexed. Greenwood Village, CO: Thomson Micromedex. 04/03/2026. Available at: http://www.micromedexsolutions.com/micromedex2/librarian. Accessed April 14, 2026.

Miller DS, Blessing JA, Krasner CN, et al. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: A study of the Gynecologic Oncology Group. J Clin Oncol. 2009;27(16):2686-2691.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Central Nervous System Cancers V3.2025. [NCCN Web site] 12/05/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Cervical Cancer V4.2025. [NCCN Web site] 12/08/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Head and Neck Cancers V1.2026. [NCCN Web site] 08/12/2025. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Malignant Peritoneal Mesothelioma. V2.2026. [NCCN Web site] 10/03/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/mpem.pdf. [login required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Malignant Pleural Mesothelioma. V2.2026. [NCCN Web site] 10/03/2025. Available from: http://www.nccn.org/professionals/physician_gls/PDF/mpm.pdf. [login required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Non-Small Cell Lung Cancer V5.2026. [NCCN Web site] 03/13/2026. Available from: http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Ovarian Cancer V4.2026. [NCCN Web site]. 04/10/2026. Available from: http://www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Thymomas and Thymic Carcinomas V2.2025. [NCCN Web site] 05/19/2025. Available at: http://www.nccn.org/professionals/physician_gls/PDF/thymic.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Thyroid Carcinoma V1.2025. [NCCN Web site] 03/27/2025. Available at: http://www.nccn.org/professionals/physician_gls/PDF/thymic.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Vaginal Cancer V2.2026. [NCCN Web site] 12/04/2025. Available at: http://www.nccn.org/professionals/physician_gls/PDF/thymic.pdf [log in required]. Accessed April 14, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Drug & Biologics Compendium. Pemetrexed. [NCCN Web site] Available at: https://www.nccn.org/professionals/drug_compendium/content/. Accessed April 14, 2026.

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

Paz-Ares L. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013;31:2895-2902.

Peters S. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;Suppl 5:v116-v119.

Pemetrexed (Pemfexy™).[prescribing information]. Woodcliff Lake, NJ. Eagle Pharmaceuticals, Inc. Updated 12/2022. Available at https://www.pemfexy.com/wp-content/uploads/2022/02/PEMFEXY-pemetrexed_injection-prescribing_information.pdf. Accessed April 14, 2026.

Raizer J, Rademaker A. Pemetrexed in the treatment of relapsed/refractory primary central nervous system. Cancer. 2011;118:3743-3748.

Ricciardi S, Tomao S, Filippo M. Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer. Ther Clin Risk Manag. 2009;5:781-787.

Scagliotti G, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage NSCLC. J Clin Oncol. 2008;26:3543-3451.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. New drug application for the use of Pemfexy (pemetrexed). [FDA Website] 02/08/2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209472s000lbl.pdf. Accessed April 14, 2026.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. (Pemfexy) Pemetrexed prescribing information and approval letter [FDA Web site]. updated 12/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed April 14, 2026.

United States National Institutes of Health, National Cancer Institute (NCI). Drug information. FDA approval Pemetrexed Disodium. [NCI Web site]. Revised 12/29/2022. Available at: https://www.cancer.gov/about-cancer/treatment/drugs/pemetrexeddisodium. Accessed April 14, 2026.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J9304 Injection, pemetrexed (Pemfexy), 10 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.00.87o:

06/15/2026

This version of the policy will become effective 06/15/2026.

The following indications were updated in the Policy section:

This policy has been updated to communicate the coverage criteria for pemetrexed (Pemfexy) in accordance with the US Food and Drug Administration (FDA) prescribing information and the National Comprehensive Cancer Network (NCCN) Compendia. NCCN updates were made for NSCLC, Central Nervous System Cancers, Malignant Pleural Mesothelioma, Ovarian Cancer, Thymomas and Thymic Carcinomas.

The following indication was removed from the policy section:

Head and Neck Cancers

Revisions From 08.00.87o:

11/17/2025

This version of the policy will become effective 11/17/2025.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Revisions From 08.00.87n:

10/01/2024

This policy has been identified for the ICD-10 code update, effective 10/01/2024.

The following ICD-10 codes has been added to Attachment A of this policy:

C83.3A Diffuse large B-cell lymphoma, in remission
C83.5A Lymphoblastic (diffuse) lymphoma, in remission
C83.7A Burkitt lymphoma, in remission
C83.8A Other non-follicular lymphoma, in remission
C83.9A Non-follicular (diffuse) lymphoma, unspecified, in remission

Revisions From 08.00.87m:

04/08/2024

This version of the policy will become effective 04/08/2024.

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia for Central Nervous System Lymphoma, Malignant Pleural Mesothelioma, Nonsquamous Non-Small Cell Lung Cancer (NSCLC) and Ovarian cancer, Fallopian Tube Cancer, and Peritoneal Cancer.

Policy title was changed from:

Pemetrexed (Alimta®), Pemetrexed (Pemfexy™)

to:

Pemetrexed (Pemfexy)

The following ICD-10 codes have been added to this policy:

C53.0 Malignant neoplasm of endocervix

C53.1 Malignant neoplasm of exocervix

C53.8 Malignant neoplasm of overlapping sites of cervix uteri

C53.9 Malignant neoplasm of cervix uteri, unspecified

C79.32 Secondary malignant neoplasm of cerebral meninges

C85.99 Non-Hodgkin lymphoma, unspecified, extranodal and solid organ sites

The following HCPCS codes have been removed from this policy:

J9294 Injection, pemetrexed (hospira) not therapeutically equivalent to j9305, 10 mg
J9296 Injection, pemetrexed (accord) not therapeutically equivalent to j9305, 10 mg
J9297 Injection, pemetrexed (sandoz), not therapeutically equivalent to j9305, 10 mg
J9305 Injection, pemetrexed, NOS 10 mg
J9322 Injection, pemetrexed (bluepoint) not therapeutically equivalent to j9305, 10 mg
J9323 Injection, pemetrexed ditromethamine, 10 mg

Revisions From 08.00.87l:

07/01/2023	This policy has been identified for the HCPCS code update, effective 07/01/2023. The following HCPCS codes have been added to this policy: J9322 Injection, pemetrexed (bluepoint) not therapeutically equivalent to j9305, 10 mg J9323 Injection, pemetrexed ditromethamine, 10 mg

Revisions From 08.00.87k:

04/01/2023

Inclusion of a policy in a Code Update memo does not imply that a full review of the policy was completed at this time.

This policy has been identified and updated for the CPT code update effective 04/01/2023.

The following HCPCs code has been added to the policy:

J9294 Injection, pemetrexed (hospira) not therapeutically equivalent to J9305,10 mg
J9296 Injection, pemetrexed (accord) not therapeutically equivalent to J9305,10 mg
J9297 Injection, pemetrexed (sandoz) not therapeutically equivalent to J9305,10 mg

Revisions From 08.00.87j:

11/07/2022

This version of the policy will become effective 11/07/2022.

The medical necessity criteria have been revised to reflect the National Comprehensive Cancer Network (NCCN) compendia for Nonsquamous Non-Small Cell Lung Cancer(NSCLC) and Ovarian cancer, Fallopian Tube Cancer, and Peritoneal Cancer, including the additional indication of Malignant Peritoneal Mesothelioma (Sarcomatoid, Epithelioid, Biphasic, Benign Multicystic, Well-Differentiated Papillary) and Low-Grade Serous Carcinoma.

The following ICD-10 codes have been added to this policy:

C45.2 Mesothelioma of pericardium
C45.7 Mesothelioma of other sites
C45.9 Mesothelioma, unspecified

The following ICD-10 codes have been removed from this policy:

C34.00 Malignant neoplasm of unspecified main bronchus

C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung

C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung

C56.9 Malignant neoplasm of unspecified ovary

C57.00 Malignant neoplasm of unspecified fallopian tube

C57.10 Malignant neoplasm of unspecified broad ligament

C57.20 Malignant neoplasm of unspecified round ligament

D15.0 Benign neoplasm of thymus

Revisions From 08.00.87i:

09/27/2021

This version of the policy will become effective 09/27/2021

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Policy criteria were updated to reflect NCCN recommendations for all indications.

New drug Pemetrexed (Pemfexy™) was added to the policy

This policy has been identified for the ICD-10 code update, effective 10/01/2021..

The following ICD-10 code has been added to this policy:

C56.3 Malignant neoplasm of bilateral ovaries

Revisions From 08.00.87h:

01/04/2020

This version of the policy will become effective 01/04/2020.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Policy criteria were updated to reflect NCCN recommendations:

Primary CNS lymphoma
Malignant pleural mesothelioma
NSCLC large cell carcinoma,
Ovarian cancer

The following indications were removed from the policy based on NCCN recommendations:

Bladder, urethral, and upper genitourinary (GU) tract cancers.

Revisions From 08.00.87g:

10/01/2020

This policy has been identified for the HCPCS code update, effective 10/01/2020.

The following HCPCS code has been revised in this policy:

J9305 Injection, pemetrexed, not otherwise specified, 10 mg

The following HCPCS code has been added to this policy:

J9034 Injection, pemetrexed (pemfexy), 10 mg

Revisions From 08.00.87f:

12/16/2019

This version of the policy will become effective 12/16/2019.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Extensive NCCN updates for policy criteria for primary carcinoma or urethra, Upper GU tumors, urothelial carcinoma of the prostate, CNS lymphoma, malignant pleural mesothelioma, and NSCLC were updated to reflect NCCN recommendations.

Revisions From 08.00.87e:

12/13/2017

This version of the policy will become effective 12/13/2017.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Policy criteria for primary carcinoma or urethra, Upper GU tumors, urothelial carcinoma of the prostate, CNS lymphoma, malignant pleural mesothelioma, and NSCLC were updated to reflect NCCN recommendations.

The following code was added: C57.9.

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

6/15/2026

Version Issued Date:

6/15/2026

Version Reissued Date:

Commercial

Medical Policy

Notification

Policy

Guidelines

Description

References

Coding

CPT Procedure Code Number(s)

ICD - 10 Procedure Code Number(s)

ICD - 10 Diagnosis Code Number(s)

HCPCS Level II Code Number(s)

Revenue Code Number(s)

MPMiscCodesNarrativesPub​

Coding and Billing Requirements

Cross Reference

Policy History

MPMiscCodesNarrativesPub