Scottish Medicines Consortium accepts use of Alimta (pemetrexed) for treatment of non-small cell lung cancer

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On 8th December 2014, the Scottish Medicines Consortium accepted for use within NHS Scotland Alimta (pemetrexed) monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer (other than predominantly squamous cell histology) in patients whose disease has not progressed immediately following platinum-based chemotherapy¹.

Rates of lung cancer in Scotland are among the highest in the world² and are significantly higher in Scotland compared with the other UK countries for both men and women³.
“Acceptance for use from the SMC is good news for Scottish patients and brings the available treatment options in line with those in England” said Phil Knott, Head of Oncology for Lilly UK. “This indication has been funded in England by the Cancer Drugs Fund since April 2013, and this news means Scottish patients can now also benefit from pemetrexed as a maintenance therapy, offering a valuable treatment option for clinicians.”

The latest acceptance from the SMC means pemetrexed is now approved in three indications for the treatment of non-small cell lung cancer and one further indication for use in the treatment of mesothelioma in Scotland. Appropriate stage IIIB/IV patients in Scotland can now be treated with pemetrexed /cisplatin until progression, followed by pemetrexed single agent as a maintenance therapy.

About Alimta (pemetrexed)

Therapeutic indications⁴

Malignant Pleural Mesothelioma:

• ALIMTA (pemetrexed) in combination with cisplatin is indicated for the treatment of chemotherapy naive patients with unresectable malignant pleural mesothelioma (MPM).

Non-Small Cell Lung Cancer:

• ALIMTA in combination with cisplatin is indicated for the first line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) other than predominantly squamous cell histology.
• ALIMTA is indicated as monotherapy for the second line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
• ALIMTA is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.

Mode of Action (MoA)

ALIMTA is a multi-targeted antifolate that disrupts the folate-dependent metabolic processes essential for cell replication. ALIMTA inhibits all folate-dependent enzymes involved in the biosynthesis of thymidine and purine nucleotides, thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT).

ALIMTA is transported into the cells, by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, ALIMTA is converted to polyglutamate forms by the enzyme folypolyglutamate synthetase. This polyglutamate is retained in the cells, where it inhibits TS, DHFR and GARFT. Polyglutamate is a time-and concentration-dependent process that occurs in tumour cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.^5,6

References

1. Alimta SMC Recommendation, http://www.scottishmedicines.org.uk Accessed 8th Dec 2014
2. Cancer Research UK, Lung Cancer Key Stats, http://www.cancerresearchuk.org/cancer-info/cancerstats/keyfacts/lung-cancer/ Updated November 2014
3. Cancer Research UK, Lung Cancer Incidence Statistics http://www.cancerresearchuk.org/cancer-info/cancerstats/types/lung/incidence/ Accessed 04 December 2014
4. Alimta Summary of Product Characteristics
5. Swainston Harrison T, Scott LJ. Pemetrexed Adis Drug Profile. Am J Cancer 2003; 2(5):359-370
6. Adjei AA. Pharmacology and mechanism of action of pemetrexed Clinical Lung Cancer 2004;5: S51-55