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Liposomal Cisplatin (Lipoplatin) in Combination with Gemcitabine for Pancreatic Cancer – First Line

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Liposomal Cisplatin (Lipoplatin) in Combination with Gemcitabine for Pancreatic Cancer – First Line Horizon Scanning Centre September 2012 Liposomal cisplatin (Lipoplatin) in combination with gemcitabine for pancreatic cancer – first line SUMMARY NIHR HSC ID: 7481 Liposomal cisplatin is intended to be used in combination with gemcitabine as first line therapy for the treatment of unresectable pancreatic cancer. If licensed, it would provide an additional treatment option for this patient group This briefing is who currently have few effective options. Liposomal cisplatin is a new formulation that targets and fuses with human tumour cells allowing for the based on specific delivery of the cytotoxic drug directly into cancer cells. This reduces information the toxicity of cisplatin and helps evade the immune system. available at the time of research and a Pancreatic cancer is the ninth most common cancer in the UK and the fifth limited literature most common cause of death from cancer. It is often diagnosed at an search. It is not advanced stage and has 1-year and 5-year survival rates of around 12% and intended to be a 3% respectively. The majority of cases occur between 60-80 years of age. In definitive statement 2008, there were 7,179 new diagnoses in England and Wales and 7,065 on the safety, deaths occurred in 2010. efficacy or effectiveness of the For unresectable pancreatic cancer, treatment is palliative. Current options health technology include gemcitabine in combination with capecitabine, FOLFIRINOX, or covered and should monotherapy with gemcitabine or fluorouracil. Liposomal cisplatin is currently not be used for in a phase III clinical trial comparing its effect on one-year survival against commercial treatment with gemcitabine alone. This trial is expected to complete in Q2 purposes or 2014. commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. NIHR Horizon Scanning Centre, University of Birmingham Email: [email protected] Web: http://www.hsc.nihr.ac.uk NIHR Horizon Scanning Centre TARGET GROUP • Pancreatic cancer: unresectable – first line; in combination with gemcitabine. TECHNOLOGY DESCRIPTION Liposomal cisplatin (Lipoplatin) is a new formulation that targets and fuses with human tumour cells allowing for the specific delivery of the cytotoxic drug directly into cancer cells. This reduces the toxicity of cisplatin and helps evade the immune system. Liposomal cisplatin is intended to be used for the treatment of unresectable pancreatic cancer and is administered by intravenous (IV) infusion at 200mg/m2 on days 1, 8 and 15 of a 21 day cycle, in combination with gemcitabine at 1,000mg/m2 on days 1 and 8 of a 21 day cycle for 3 cycles or until disease progression. Liposomal cisplatin is in phase III clinical trials for non-small cell lung cancer, head and neck cancer and ovarian cancer, and in phase II trials for gastric cancer. INNOVATION and/or ADVANTAGES If licensed, liposomal cisplatin will provide an additional treatment option for this patient group who currently have few effective options. DEVELOPER Regulon Inc. AVAILABILITY, LAUNCH OR MARKETING In phase III clinical trials. PATIENT GROUP BACKGROUND Pancreatic cancer is the ninth most common cancer in the UK and the fifth most common cause of death from cancer1. It may arise in the head, body or tail of the pancreas and symptoms, which include jaundice, nausea, diarrhoea, weight loss, loss of appetite and severe pain, vary depending on the tumour site2,3. There are three main types described: infiltrating ductal adenocarcinomas, which account for around 90% of pancreatic cancers, acinar cell carcinoma, and pancreatoblastoma4. NHS or GOVERNMENT PRIORITY AREA This topic is relevant to: • Improving Outcomes: A Strategy for Cancer (2011). 2 NIHR Horizon Scanning Centre CLINICAL NEED and BURDEN OF DISEASE Pancreatic cancer has one of the worst prognoses of all solid tumours, with >95% of those affected dying of their disease4. The high mortality rate is, at least in part, due to the vast majority of patients presenting at an advanced stage3. Patients with unresectable, locally advanced disease have a median survival of 6-11 months, and patients with metastatic disease have a median survival of 2-6 months5. The 1-year survival rate is low, at around 12%, and less than 3% survive to 5 years3. Pancreatic cancer affects both sexes equally, with a lifetime risk of 1 in 77 for men and 1 in 79 for women6. It is rare before the age of 45 years; 80% of cases occur between 60-80 years of age7. In 2008, there were 7,179 new diagnoses in England and Wales6, and 7,065 deaths occurred in 20108. In 2010-11, there were 23,893 hospital admissions due to pancreatic cancer in England, accounting for 30,016 finished consultant episodes and 98,426 bed days9 (ICD C25). PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE technology appraisal. The use of gemcitabine for the treatment of pancreatic cancer (TA25). 20013. • NICE interventional procedure guidance in development. IRE for the treatment of pancreatic cancer. Expected winter 201310. Other Guidance • ESMO. Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 20104. • Pancreatic Section of the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, and Royal College of Pathologists, Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer, periampullary and ampullary carcinomas. 20057. EXISTING COMPARATORS and TREATMENTS Curative surgery is currently a treatment option for only around 4% of the overall patient population3. As the majority of cases are diagnosed at advanced stages, the aim of treatment is usually palliative; to improve quality of life and relieve symptoms1. Current options include3,5: • Chemotherapy – gemcitabine in combination with capecitabine, FOLFIRINOX (fluorouracil, oxaliplatin and irinotecan); or monotherapy with gemcitabine or fluorouracil alone (if combination chemotherapy contraindicated). • Second line therapy may be considered for a small proportion of patients, if fit enough for subsequent treatment – fluoropyrimidines (fluorouracil or capecitabine) or oxaliplatin in combination with gemcitabine. • Concurrent chemo-radiotherapy – for locally advanced disease only. • Palliative surgery and endoscopic placement of biliary drainage stents to control symptoms such as jaundice and gastric outlet obstruction. 3 NIHR Horizon Scanning Centre • Palliative radiotherapy for control of symptoms associated with localised disease such as pain. EFFICACY and SAFETY Trial EUCTR2011-003601-25-GR, LipoGem- EUCTR2006-005485-40-GR, LipoGem- PII-1L-Pancr; liposomal cisplatin with PII-1L-Pancr; liposomal cisplatin with gemcitabine vs gemcitabine alone; phase gemcitabine; phase II. III. Sponsor Regulon AE. Regulon AE. Status Ongoing. Ongoing. Source of Trial registry11, manufacturer. Trial registry12, manufacturer. information Location EU (inc UK), USA and other countries. Greece. Design Randomised, active-controlled. Non-randomised, single arm. Participants n=328 (planned); adults; pancreatic n=61 (planned); adults aged 18-70 years; cancer; locally advanced or metastatic pancreatic cancer; unresectable, locally adenocarcinoma; no prior treatment. advanced or metastatic adenocarcinoma; chemotherapy naïve. Schedule Randomised to: Liposomal cisplatin, IV, 120mg/m2 on Arm 1: Liposomal cisplatin, IV, 200mg/m2, days 1, 8 and 15 of 21 day cycle, with plus gemcitabine, IV, 1,000mg/m2 on days gemcitabine, IV, 1,000mg/m2 on days 1 1 and 8 of 21 day cycle, both for 3 cycles. and 8 of 21 day cycle, both for 3 cycles. Patients without disease progression Patients without disease progression continue for 3 additional cycles. Then, continue with maintenance liposomal patients without disease progression cisplatin, IV, 120mg/m2 and gemcitabine, continue with maintenance liposomal IV, 1,000mg/m2 on days 1 and 15 of 28 cisplatin, IV, 200mg/m2 every 8 weeks. day cycle. Arm 2: gemcitabine, IV, 1,000mg/m2 on days 1, 8 and 15 of a 21 day cycle for 3 cycles. Patients without disease progression continue for 3 further cycles. Follow-up Active treatment period 18 weeks followed Active treatment period 9 weeks followed by maintenance therapy until disease by maintenance therapy until disease progression; follow-up until death. progression; follow-up until death. Primary One year survival; overall survival (OS). Disease control ratea; OS. outcome/s Secondary Progression-free survival (PFS); objective 1 year survival; toxicity; PFS; ORR; QoL; outcome/s response rate (ORR); quality of life (QoL); safety. safety. Expected Q2 2014. Q4 2013. reporting date COST and IMPACT ESTIMATED COST The cost of liposomal cisplatin is not yet known. a Defined as the sum of complete response, partial response and stable disease at week 9. 4 NIHR Horizon Scanning Centre IMPACT - SPECULATIVE Impact on Patients and Carers Reduced mortality/increased length of survival Reduced symptoms or disability Other: No impact identified Impact on Services Increased use of existing services if more Decreased use of existing services patients suitable for chemotherapy Re-organisation of existing services Need for new services Other: None identified Impact on Costs Increased drug treatment costs Reduced drug treatment costs Other
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