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Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.
Pemetrexed is a multitargeted antifolate that inhibits thymidylate synthase, DHFR and GARFT, starving cells of the nucleotides needed for DNA synthesis. In EMPHACIS (2003), cisplatin-pemetrexed gave OS 12.1 versus 9.3 months compared with cisplatin alone, the first randomised survival gain in mesothelioma, and it became the first approved treatment for the disease in 2004. It is now given with pembrolizumab (KEYNOTE-483) or bevacizumab (MAPS), and it was the chemotherapy comparator that nivolumab-ipilimumab beat in CheckMate 743. It is also standard in non-squamous NSCLC, dosed at 500 mg/m2 every 21 days with a platinum for 4 to 6 cycles, then optional maintenance. Folic acid and vitamin B12 supplementation and dexamethasone premedication are required. It remains the chemotherapy backbone in mesothelioma that newer agents are added to rather than replacing.
Multitargeted antifolate inhibiting thymidylate synthase, DHFR, and GARFT.
1.Enters cells via the reduced folate carrier
Given by infusion or injection in a clinic or hospital outpatient department, so it is a Part B drug: Medicare pays 80% after the Part B deductible and the patient owes 20% coinsurance, uncapped in Original Medicare unless a Medigap policy applies. HCPCS J9305 for Alimta; generics and Pemfexy/Pemrydi RTU have separate codes with different patient coinsurance.
Multi-source generic; covered under the medical benefit without prior authorisation in most plans, as part of standard regimens. Plans increasingly prefer generic pemetrexed over Alimta.
Sources: Medicare.gov: Chemotherapy · Medicare.gov: Prescription drugs (outpatient, Part B). Not medical or financial advice; verify with your plan.
Sources: NICE TA181 · SMC advice: pemetrexed. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
As a single agent for locally advanced or metastatic NSCLC after prior chemotherapy
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
Non-squamous NSCLC: 1) as initial treatment with cisplatin; 2) as a single agent after prior chemotherapy
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
As a single agent for locally advanced or metastatic NSCLC after prior chemotherapy
Confirmed: the accelerated approval of 2004 converted to traditional approval 4.9 years after it was granted.
Non-squamous NSCLC: 1) as initial treatment with cisplatin; 2) as a single agent after prior chemotherapy
Confirmed: the accelerated approval of 2008 converted to traditional approval 0.8 years after it was granted.
In combination with pembrolizumab and carboplatin for first-line treatment of metastatic non-squamous NSCLC
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
In combination with pembrolizumab and carboplatin for first-line treatment of metastatic non-squamous NSCLC
Confirmed: the accelerated approval of 2018 converted to traditional approval 0.7 years after it was granted.
| Region | Year | Indication |
|---|---|---|
| US | 2004 | Unresectable pleural mesothelioma with cisplatin |
| US | 2008 | Non-squamous NSCLC first line |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia (grade 3+) | - | 23% |
| Fatigue | 48% | - |
| Nausea | 82% | - |
| Rash | 16% | - |
Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
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Adding chemotherapy to osimertinib delays progression. Whether it extends life, and whether the same benefit could be had by giving the chemotherapy later to the patients who need it, is what the overall survival analysis and the registry watch on this roadmap are for.
The moment lung cancer stopped being one disease for treatment purposes. Before this trial the pathology report said cancer or not cancer; after it, the subtype chose the drug, and the tissue had to be preserved well enough to answer the question.
Platinum-pemetrexed remains the chemotherapy backbone in mesothelioma, now combined with pembrolizumab or bevacizumab, or replaced by dual immunotherapy in non-epithelioid disease.
Query for this drug: (TITLE:"Pemetrexed" OR ABSTRACT:"Pemetrexed" OR TITLE:"Alimta" OR ABSTRACT:"Alimta" OR TITLE:"and generics" OR ABSTRACT:"and generics") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Pemetrexed, not a curated reading list.
Shares Study of STK-012 Alone and With Other Treatments in Patients With Advanced Lung Cancer and Other Cancers, Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors, A Phase II Study of SSGJ-706 Monotherapy and Combination Therapy in Advanced Non-Small Cell Lung Cancer（NSCLC） Patients, A Study to Evaluate the Safety and Efficacy of HB0025 Injection in Patients With Advanced Solid Tumor.
Shares Phase 3 trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma, A Study to Compare Pharmacokinetics, Efficacy, Safety, and Immunogenicity of MB12 (Proposed Pembrolizumab Biosimilar) to Keytruda® in Non-small Cell L, JMT101 in Combination With Osimertinib, Versus Cisplatin-pemetrexed in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Chara, Study of Pemetrexed+Platinum Chemotherapy With or Without Cosibelimab in First Line Metastatic Non-squamous NSCLC.
Shares A Study to Evaluate the Safety and Efficacy of HB0025 Injection in Patients With Advanced Solid Tumor, Volrustomig Priming Regimens Exploratory Phase II Platform Study, A Global Study of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for Participants With Metastatic Non-small Cell Lung, A Study To Assess the Safety, Tolerability, and Efficacy of Imzokitug in Combination With Pumitamig and Platinum-Doublet Chemotherapy (PDCT) Versus Pu.
Shares Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC, Study of STK-012 Alone and With Other Treatments in Patients With Advanced Lung Cancer and Other Cancers, A Study Comparing BL-B01D1 With Platinum Based Chemotherapy in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer(PANKU-Lung01), A Study of BH-30643 in Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations.
Shares A Study of LP-300 With Carboplatin and Pemetrexed in Never Smokers With Advanced Lung Adenocarcinoma, JMT101 in Combination With Osimertinib, Versus Cisplatin-pemetrexed in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Chara, Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer, A Study of TY-9591 With Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor NSCLC.
Shares De-escalation Immunotherapy mAintenance Duration Trial for Stage IV Lung Cancer Patients With Disease Control After Chemo-immunotherapy Induction, JYP0322 Versus Platinum Based Doublet Chemotherapy in ROS1 Positive Patients Previously Treated With ROS1-TKIs., Efficacy and Safety Evaluation of PLB1004 in Patients With Non-squamous NSCLC Harboring EGFR Exon 20 Insertion., Efficacy and Biomarker Development for Lung Cancer Treated With Immune Checkpoint Inhibitors.
Shares Safety, Immunogenicity and Preliminary Clinical Activity Study of PDC*lung01 Cancer Vaccine in NSCLC, A Phase 1/2 Study of BA3071 in Patients With Solid Tumors, Efficacy and Biomarker Development for Lung Cancer Treated With Immune Checkpoint Inhibitors, Study of Eftilagimod Alfa (Efti) in Combination With Pembrolizumab and Chemotherapy Versus Placebo in Combination With Pembrolizumab and Chemotherapy .
Shares A Clinical Trial of LBL-024 Combination Drug in Patients With Advanced Solid Tumours[Substudy 01(NSCLC)], LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib, DZD6008 Combination Therapy in Patients With Locally Advanced or Metastatic NSCLC With EGFR Mutation (TIAN-SHAN7), A Phase I/II Study of CS2009 in Participants With Advanced Solid Tumors.