Ireland Latest News

New Treatment Now Available for Patients with Refractory Metastatic Colorectal Cancer

HSE reimburses Servier’s ▼Lonsurf®(trifluridine/tipiracil)

Dublin, Ireland [1st February, 2017] – Servier Ireland today announced that Lonsurf® (trifluridine/tipiracil) is now reimbursed in Ireland under the High Tech Scheme, within its marketing authorisation, as an option for treating metastatic colorectal cancer. LONSURF® is indicated in adults who have had previous treatment with available therapies including fluoropyrimidine - oxaliplatin- or irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) agents and anti-epidermal growth factor receptor (EGFR) agents, or when these therapies are not suitable. LONSURF® was trialled in three centres in Ireland; Bon Secours Hospital, Cork, Adelaide and Meath Hospital, Dublin and St Vincent’s Hospital, Dublin during the pivotal phase III RECOURSE study.

This announcement comes at a time when there is a real need for further treatment options for patients with refractory metastatic colorectal cancer. With the changing funding landscape for new treatments in Ireland, the addition of new products in later lines of therapy could be crucial to those patients.

“Data from the pivotal RECOURSE study provides evidence that LONSURF may offer Irish patients with refractory metastatic colorectal cancer extended survival as well as a reduction in risk of death compared to placebo”, said Professor Ray McDermott, Consultant Medical Oncologist, Tallaght Hospital, Dublin and one of the Irish RECOURSE investigators. “There are not many options left when a patient has had previous treatments. LONSURF is potentially a valuable new treatment that I can offer to my patients with metastatic colorectal cancer regardless of their RAS status or resistance to previous lines of treatment”, continued McDermott.

Servier welcomes the HSE’s decision and the positive news it brings for patients with metastatic colorectal cancer and their families. The HSE reimbursement comes after marketing authorisation was granted by the European Commission in May and the NICE recommendation in August 2016 based on data from the Phase III RECOURSE study. Servier is an international pharmaceutical company, with no shareholders, governed by a non-profit Foundation. The recommendation underpins the company’s commitment to research in the field of oncology and its philosophy of delivering life-enhancing medicines to the patients who need them.

“With this approval, we are delivering on a promise to bring an oral new treatment to patients with advanced metastatic colorectal cancer across Europe,” said Mr Francois Druguet, Country Manager Servier Ireland. “We are excited about this important milestone, which demonstrates Servier’s commitment to improving the lives of patients living with cancer. LONSURF has also been shown to prolong progression-free survival and preserve performance status, allowing patients to make time for more moments that matter.”

In coming to their decision, the HSE considered evidence from the international, double-blind, placebo-controlled Phase III RECOURSE study, which investigated the efficacy and safety of trifluridine/tipiracil plus best supportive care (BSC) compared to placebo plus BSC in 800 patients with previously treated mCRC.1 The trial met the primary endpoint of a statistically significant improvement in overall survival (OS).1 The median OS improved from 5.2 months with placebo (+BSC) to 7.2 months with trifluridine/tipiracil (+BSC).2 The hazard ratio for death in the trifluridine/tipiracil group versus the placebo group was 0.69 (95% confidence interval [CI], 0.59 to 0.81; P<0.0001), this translated into 1-year survival rates of 27.1% and 16.6%, respectively.2

The most frequently observed side effects (≥ 30%) in patients receiving trifluridine/tipiracil were neutropenia, nausea, decreased appetite, diarrhoea, fatigue, anaemia, thrombocytopenia, increase in total bilirubin, alkaline phosphatase and AST levels, and leucopenia.1,3


1 - Mayer R, et al. New England Journal of Medicine. 2015;372:1909-1919.
2 - Mayer R, et al. Journal of Clinical Oncology 34, 2016 (suppl 4S; abstr 634)
3 - Lonsurf SPC available at http://www.medicines.ie/medicine/16726/SPC Accessed October 2016

Subject to additional monitoring. Lonsurf® (trifluridine/tipiracil) Abbreviated prescribing information: COMPOSITION*: Lonsurf 15 mg/6.14 mg: film-coated tablet containing 15 mg trifluridine and 6.14 mg tipiracil (as hydrochloride). Lonsurf 20 mg/8.19 mg: film-coated tablet containing 20 mg trifluridine and 8.19 mg tipiracil (as hydrochloride). INDICATION*: Treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti EGFR agents. DOSAGE AND ADMINISTRATION*: Recommended starting dose: 35 mg/m2/dose taken orally twice daily on Days 1 to 5 and Days 8 to 12 of each 28-day cycle, within 1 hour after completion of the morning and evening meals. Dosage calculated according to body surface area, not exceeding 80 mg/dose. Possible dosing adjustments based on individual safety and tolerability: 3 permitted dose reductions to a minimum dose of 20 mg/m2 twice daily, dose escalation permitted after a dose reduction. CONTRAINDICATIONS*: Hypersensitivity to the active substances or to any of the excipients. WARNINGS*: Bone marrow suppression: Complete blood cell counts must be obtained prior to initiation of therapy, prior to each cycle and as needed. Treatment must not be started if absolute neutrophil count <1.5 x109/L, if platelet counts <75x109/L, or if unresolved Grade 3 or 4 non-haematological clinically relevant toxicity. Patient should be monitored closely for infections, appropriate measures should be administered as clinically indicated. Gastrointestinal toxicity: anti-emetic, anti-diarrhoeal and other measures should be administered as clinically indicated, dose modifications should be applied as necessary. Renal impairment: not recommended if severe renal impairment or end-stage renal disease. Patients with moderate renal impairment should be more frequently monitored for haematological toxicities. Hepatic impairment: not recommended if moderate or severe hepatic impairment. Proteinuria: monitoring by dipstick urinalysis recommended prior to starting and during therapy. Excipients: contain lactose. INTERACTIONS*: Precautions: medicinal products that interact with nucleoside transporters CNT1, ENT1 and ENT2, inhibitors of OCT2 or MATE1, human thymidine kinase substrates (e.g. zidovudine), hormonal contraceptives. FERTILITY*. PREGNANCY AND BREASTFEEDING*: Not recommended. CONTRACEPTION*: For women and men, highly effective contraceptive measures must be used during treatment and for 6 months after stopping treatment. DRIVE & USE MACHINES*: Fatigue, dizziness or malaise may occur. UNDESIRABLE EFFECTS*: Very common: Neutropenia, leukopenia, anaemia, thrombocytopenia, decreased appetite, diarrhoea, nausea, vomiting, fatigue. Common: Lower respiratory tract infection, upper respiratory tract infection, febrile neutropenia, lymphopenia, monocytosis, hypoalbuminaemia, insomnia, dysgeusia, neuropathy peripheral, dizziness, headache, flushing, dyspnoea, cough, abdominal pain, constipation, stomatitis, oral disorder, hyperbilirubinaemia, Palmar-plantar erythrodysaesthesia syndrome, rash, alopecia, pruritus, dry skin, proteinuria, pyrexia, oedema, mucosal inflammation, malaise, hepatic enzyme increased, blood alkaline phosphatase increased, weight decreased. Uncommon: Septic shock, enteritis infectious, lung infection, biliary tract infection, influenza, urinary tract infection, gingival infection, herpes zoster, tinea pedis, candidiasis, bacterial infection, infection, cancer pain, pancytopenia, granulocytopenia, monocytopenia, erythropenia, leukocytosis, dehydration, hyperglycaemia, hyperkalaemia, hypokalaemia, hypophosphataemia, hypernatraemia, hyponatraemia, hypocalcaemia, gout, anxiety, neurotoxicity, dysaesthesia, hyperaesthesia, hypoaesthesia, syncope, paraesthesia, burning sensation, lethargy, visual acuity reduced, vision blurred, diplopia, cataract, conjunctivitis, dry eye, vertigo, ear discomfort, angina pectoris, arrhythmia, palpitations, embolism, hypertension, hypotension, pulmonary embolism, pleural effusion, rhinorrhoea, dysphonia, oropharyngeal pain, epistaxis, enterocolitis haemorrhagic, gastrointestinal haemorrhage, pancreatitis acute, ascites, ileus, subileus, colitis, gastritis, reflux gastritis, oesophagitis, impaired gastric emptying, abdominal distension, anal inflammation, mouth ulceration, dyspepsia, gastrooesophageal reflux disease, proctalgia, buccal polyp, gingival bleeding, glossitis, periodontal disease, tooth disorder, retching, flatulence, breath odour, hepatotoxicity, biliary dilatation, skin exfoliation, urticaria, photosensitivity reaction, erythema, acne, hyperhidrosis, blister, nail disorder, joint swelling, arthralgia, bone pain, myalgia, musculoskeletal pain, muscular weakness, muscle spasms, pain in extremity, sensation of heaviness, renal failure, cystitis noninfective, micturition disorder, haematuria, leukocyturia, menstrual disorder, general physical health deterioration, pain, feeling of body temperature change, xerosis, blood creatinine increased, electrocardiogram QT prolonged, international normalised ratio increased, activated partial thromboplastin time prolonged, blood urea increased, blood lactate dehydrogenase increased, protein total decreased, C-reactive protein increased, haematocrit decreased. Post-marketing experience: interstitial lung disease reported in Japanese patients. OVERDOSE*. PROPERTIES*: Trifluridine is an antineoplastic thymidine-based nucleoside analogue and tipiracil hydrochloride is a thymidine phosphorylase (TPase) inhibitor. Following uptake into cancer cells, trifluridine, is phosphorylated by thymidine kinase, further metabolised in cells to a deoxyribonucleic acid DNA substrate, and incorporated directly into DNA, preventing cell proliferation. However, trifluridine is rapidly degraded by TPase and readily metabolised by a first-pass effect following oral administration, hence the inclusion of the TPase inhibitor, tipiracil hydrochloride. PRESENTATION*: Pack of 20 or 60 film-coated tablets. LES LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. www.servier.com. Marketing Authorisation: EU/1/16/1096/001-006. Legal Category: POM. Date of Text: April 2016. Further information available from: Servier Laboratories Ireland Ltd, Block 2, West Pier Business Campus, Old Dunleary Road, Dun Laoghaire, Co. Dublin, Tel (01) 6638110, Fax (01) 6638120, www.servier.ie.

* For complete information, please refer to the Summary of Product Characteristics on www.medicines.ie.

 


1617C1LNPRDig. Date of Preparation: February 2017.
This is intended for healthcare professionals only.