Pemetrexed is a folate analog metabolic inhibitor that is indicated for the use to treat certain cancers.

FDA Approved Indications
The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of the following conditions:

• Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer as:
  • Initial treatment in combination with cisplatin; or
  • Maintenance treatment of patients whose disease has not progressed after four cycles of platinum-based first-line chemotherapy; or
  • After prior chemotherapy as a single-agent; or
• Mesothelioma: in combination with cisplatin.

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered.

NCCN Approved Indications

Bladder Cancer

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of bladder cancer when:

• Used as a single agent for clinical stage T4b or T2-4a, N1-3 disease, or for recurrence post cystectomy, or for metastatic disease as subsequent systemic therapy.

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of bladder cancer- primary carcinoma of the urethra when:

• Used as a single agent as subsequent systemic therapy for recurrent or metastatic disease.

Note: Chemotherapy regimen based on histology. See Non-Urothelial and Urothelial with Variant Histology (BL-D) if appropriate.

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of bladder cancer/ upper GU tract tumors when:

• Used as a single agent as subsequent systemic therapy for metastatic disease.

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of bladder cancer- urothelial carcinoma of the prostate when:

• Used as a single agent as subsequent systemic therapy for metastatic disease.

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered.

Central Nervous System Cancers - Primary CNS Lymphoma

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of Central Nervous System Cancers - Primary CNS Lymphoma when used as a:

• Single-agent treatment for progressive or recurrent disease in patients who have received prior methotrexate-based regimen without prior radiation therapy (RT):
  • After prolonged (equal or greater than 12 months) response to prior regimen; or
  • In combination with RT after short (less than 12 months) or no response to prior regimen; or
• Systemic treatment as a single agent for progressive or recurrent disease;
  • May be considered in patients with prior whole brain radiation therapy; or
  • In patients who received prior high-dose chemotherapy with stem cell rescue after a prolonged response (greater than or equal to 12 months).

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered. 

Cervical Cancer

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of cervical cancer as a:

• Second-line therapy as a single agent for:
  • Local/regional recurrence; or
  • Distant metastases.

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered.

Malignant Pleural Mesothelioma

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of malignant pleural mesothelioma when used as:

• Induction chemotherapy in combination with cisplatin for medically operable clinical stage I-III disease; or
• Used as a single agent or in combination with carboplatin or cisplatin as treatment of:
  • Unresectable clinical stage I-III disease and tumors of epithelial histology; or
  • Resected clinical stage I-III disease in patients not treated with induction chemotherapy; or
  • Clinical stage IV disease, tumors of sarcomatoid or mixed histology, or medically inoperable tumors in patients with performance status (PS) 0-2; or

• Used in combination with bevacizumab and cisplatin as treatment of:
  • Unresectable clinical stage I-III disease and tumors of epithelial histology: or
  • Clinical stage IV disease, tumors of sarcomatoid or mixed histology, or medically inoperable tumors in patients with performance status (PS) 0-2; or
• Second-line chemotherapy as a single agent:
  • If not administered first-line; or
  • As rechallenge if good sustained response at the time initial chemotherapy was interrupted (if administered first-line).

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered.

Non-Small Cell Lung Cancer (NSCLC)

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of NSCLC when used as:

• Preoperative concurrent chemoradiation in combination with carboplatin or cisplatin for:
  • Resectable or possibly resectable superior sulcus tumors (T3 invasion or T4 extension, N0-1); or
  • T3 invasion or resectable T4 extension, N0-1 disease in the chest wall, proximal airway, or mediastinum; or
• Combination with cisplatin:
  • May be used as induction chemotherapy for operable stage IB (peripheral T2a, N0), stage I (central T1ab-2a, N0), stage II (T1ab-2ab, N1 or T2b, N0), stage IIB (T3, N0), or stage IIIA (T3, N1) with negative mediastinal nodes as an alternative for patients likely to receive adjuvant chemotherapy; or
  • As neoadjuvant chemotherapy for T3 invasion or resectable T4 extension, N0-1 disease in the chest wall, proximal airway, or mediastinum; or
  • As induction chemotherapy with or without radiation for T1-2 or T3 (other than invasive) N2, M0; or
  • May be used as induction chemotherapy for T1-3, N0-1 (including T3 with multiple nodules in the same lobe) as an alternative for patients likely to receive adjuvant chemotherapy; or

• Initial treatment as definitive concurrent chemoradiation in combination with carboplatin or cisplatin (with or without an additional 4 cycles of pemetrexed after concurrent chemoradiation if given with cisplatin) for:
  • Medically inoperable stage IB (peripheral T2a, N0), stage I (central T1ab-2a, N0), stage II (T1ab-2ab, N1 or T2b, N0), stage IIB (T3, N0), or stage IIIA (T3, N1) with negative mediastinal nodes and N1 disease; or
  • Unresectable superior sulcus tumors (T4 extension, N0-1); or
  • Unresectable stage IIIA (T4, N0-1); or
  • T1-2 or T3 (other than invasive), N2 nodes positive, M0; or
  • T3 invasion, N2 nodes positive, M0; or
  • Stage IIIB (T1-3, N3 positive, M0); or
  • Contralateral or ipsilateral mediastinal node-positive stage IIIB (T4 extension, N2-3); or
  • Stage IV, M1b disease and limited non-brain metastases confirmed, if definitive therapy for thoracic disease is feasible; or
• Adjuvant chemotherapy in combination with cisplatin:
  • May be considered following definitive radiation therapy in medically inoperable high-risk stage IB (peripheral T2a, N0), stage I (central T1ab-2a, N0), stage II (T1ab- 2ab, N1; T2b, N0), stage IIB (T3, N0), or stage IIIA (T3, N1) with negative mediastinal nodes and N0 disease; or
  • For high-risk, margin-negative stage IB (T2a, N0) and IIA (T2b, N0); or
  • For margin-positive stage IB (T2a, N0) and IIA (T2b, N0); or
  • For margin-positive stage IIA (T2b, N0) following radiation; or
  • For stage IIA (T1ab-2a, N1) and IIB (T3, N0; T2b, N1); or
  • For margin-negative stage IIIA (T1-3, N2; T3, N1); or
  • For resectable superior sulcus tumors (T3 invasion or T4 extension, N0-1); or
  • For T3 invasion or resectable T4 extension, N0-1 tumors in the chest wall, proximal airway, or mediastinum if not given as initial treatment; or
  • For clinical stage IIIA disease (T1-3, including T3 with multiple nodules in the same lobe) that was clinically N2 but has negative N2, N3 nodes on mediastinal biopsy and negative margins post-surgery; or
  • For clinical stage IIIA disease (T1-2, T3 other than invasive, N2 nodes positive, M0) with no apparent progression or local progression after induction chemotherapy; or
  • For separate pulmonary nodule(s) in the same lobe (T3) or ipsilateral non-primary lobe (T4), N0-1; or
  • For margin-negative or margin-positive, R1 separate pulmonary nodule(s) in the same lobe (T3) or ipsilateral non-primary lobe (T4), N2; or

• Adjuvant concurrent chemoradiation in combination with carboplatin or cisplatin (with or without an additional 4 cycles of pemetrexed after concurrent chemoradiation if given with cisplatin) for:
  • Margin-positive stage IIA (T1ab-2a, N1) and IIB (T3, N0; T2b, N1); or
  • Margin-positive stage IIIA (T1-3, N2; T3, N1); or
  • Margin-positive T3 invasion or resectable T4 extension, N0-1 tumors in the chest wall, proximal airway, or mediastinum if not given as initial treatment; or
  • Clinical stage IIIA disease (T1-3, including T3 with multiple nodules in the same lobe) that was clinically N2 but has negative N2, N3 nodes on mediastinal biopsy and positive margins post-surgery; or
  • Margin-positive separate pulmonary nodule(s) in the same lobe (T3) or ipsilateral non-primary lobe (T4), N2; or
• Concurrent chemoradiation in combination with carboplatin or cisplatin (with or without an additional 4 cycles of pemetrexed after concurrent chemoradiation if given with cisplatin) if radiation not previously given for locoregional recurrence in the mediastinal lymph nodes or for superior vena cava obstruction; or
• Treatment for recurrence or metastasis for tumors of nonsquamous cell histology as a single agent for patients with performance status (PS) 2, in combination with cisplatin for (PS) 0-1, or in combination with carboplatin for (PS) 0-2 as:
  • First-line therapy for EGFR, ALK, ROS1, and PD-L1 negative or unknown; or
  • Subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, or osimertinib therapy; or
  • Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, or alectinib therapy; or
  • Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib therapy; or
  • Subsequent therapy for PD-L1 expression-positive (greater than or equal to 50%) and EGFR, ALK, and ROS1 negative tumors and prior pembrolizumab therapy; or

• Treatment for recurrence or metastasis in combination with bevacizumab and cisplatin or carboplatin for patients with performance status 0-1, tumors of nonsquamous cell histology, and no history of recent hemoptysis as:
  • First-line therapy for EGFR, ALK, ROS1, and PD-L1 negative or unknown; or
  • Subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, or osimertinib therapy; or
  • Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, or alectinib therapy; or
  • Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib therapy; or
  • Subsequent therapy for PD-L1 expression-positive (greater than or equal to 50%) and EGFR, ALK, and ROS1 negative tumors and prior pembrolizumab therapy; or
• Treatment for recurrence or metastasis of nonsquamous cell histology in patients with performance status 0-2 who achieve tumor response or stable disease following chemotherapy:
  • As a single agent for continuation maintenance therapy if previously used with a first-line chemotherapy regimen; or
  • In combination with bevacizumab if bevacizumab previously used with a first-line pemetrexed/platinum chemotherapy regimen; or
  • As a single agent for switch maintenance; or 

• Single agent (if not already given) as subsequent therapy for metastatic disease in patients with performance status 0-2 and tumors of nonsquamous cell histology:
  • Following progression on a first-line cytotoxic regimen; or
  • For further progression on a systemic immune checkpoint inhibitor or other systemic therapy.

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered.

Ovarian Cancer - Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of ovarian cancer - epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer when used as a:

• Single-agent therapy for persistent disease or recurrence.

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered.

Thymomas and Thymic Carcinomas

The use of pemetrexed (Alimta®) may be considered medically necessary when used in the treatment of thymomas and thymic carcinomas when used as a:

• Second-line therapy as a single agent.

The use of pemetrexed (Alimta®) for any other indication not listed on this policy will be considered not medically necessary, and therefore, non-covered.

Pemetrexed (Alimta®) is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances including, but not limited to the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.