Erlotinib (Tarceva) for non small cell lung cancer advanced or metastatic maintenance monotherapy

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1 Erlotinib (Tarceva) for non small cell lung cancer advanced or metastatic maintenance monotherapy September 2008 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The Research Programme is part of the National Institute for Health Research

2 Erlotinib (Tarceva) for non small cell lung cancer advanced or metastatic maintenance monotherapy Target group Non small cell lung cancer (NSCLC): advanced or metastatic (stage IIIB and IV) with at least stable disease after first line platinum-based chemotherapy maintenance monotherapy to prevent or delay disease progression. Technology description Erlotinib hydrochloride (Tarceva, CP , OSI-774, R-1415) is an orally-active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the underlying molecular mechanisms involving oncogenes and tumour suppressor genes that play critical roles in the conversion of normal cells into a cancerous state. It is anticipated that erlotinib will be used as an addition to existing treatment. The use of erlotinib as maintenance therapy will preclude its use in patients on progression as a second-line therapy, since progression on erlotinib implies resistance to the drug. Erlotinib is administered at 150mg daily. The regulatory study for erlotinib maintenance may include a requirement for patient selection on the basis of tumour biomarkers. Erlotinib is currently licensed for second line monotherapy for locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Erlotinib is in phase III clinical trials for colorectal cancer, head and neck cancer, and as maintenance therapy in NSCLC in combination with bevacizumab. Innovation and/or advantages If licensed, erlotinib will be the first orally-active non-cytotoxic drug approved for use as monotherapy to maintain remissions in NSCLC that is non-progressive after cytotoxic chemotherapy. Developer Roche. Availability, launch or marketing dates, and licensing plans: In phase III clinical trials. NHS or Government priority area: The topic is relevant to the Cancer Reform Strategy (2007) and the NHS Cancer Plan (2000). Relevant guidance NICE technology appraisal in development. Erlotinib for advanced non-small cell lung cancer. Expected November NICE technology appraisal in development. Gefitinib for non-small cell lung cancer. Expected November NICE technology appraisal in development. Cetuximab for advanced non-small cell lung cancer. Expected date of issue to be announced 3. NICE technology appraisal. Bevacizumab for non-small cell lung cancer. Terminated NICE technology appraisal. Pemetrexed disodium for the treatment of mesothelioma

3 NICE technology appraisal. Pemetrexed for the treatment of non-small cell lung cancer NICE clinical guideline. Lung Cancer: the diagnosis and treatment of lung cancer (expected review date February 2009) 7. National Comprehensive Cancer Network (NCCN). Clinical practice guideline on non-small cell lung cancer SIGN. Management of patients with lung cancer European Society for Medical Oncology (ESMO). Minimum clinical recommendations for the diagnosis, treatment and follow-up of non-small cell lung cancer Clinical need and burden of disease Lung cancer is the second most common cancer diagnosed in the UK. In England and Wales there were 33,183 new cases diagnosed in 2005, with 29,271 registered deaths in In England and Wales lung cancer has a one-year survival rate of 25% and a fiveyear survival rate of 7% 12. NSCLC accounts for approximately 75% of all lung cancers 13. Approximately 75% of newly diagnosed patients already have advanced (stage III or IV) disease 14 (around 24,887 patients in England and Wales), with a five-year survival rate of less than 1% 15. Existing comparators and treatments Maintenance therapy is currently not part of standard care, therefore no clear comparator exists. Treatment options for stage IIIB or IV NSCLC include radiation therapy, chemotherapy with radiation therapy, and chemotherapy alone. Chemotherapy may be recommended for patients with non-resectable stage III or IV disease provided they have a good performance status (PS) a. Current NICE guidance recommends that first-line chemotherapy should include a combination of a platinum drug (cisplatin or carboplatin) and a single third generation drug, such as docetaxel, gemcitabine, pacitaxel or vinorelbine. Efficacy and safety Trial code, name SATURN; BO18192: NSCLC; erlotinib maintenance therapy after first line chemotherapy; phase III 16. NCT : NSCLC; maintenance chemotherapy vs. erlotinib; phase III. Previously treated NSCLC; erlotinib vs. placebo; phase III. Sponsor Roche. Hospices Civils de Lyon. University of Toronto. Status Recruitment complete. Ongoing. Published 18. Location Worldwide. France. - Design Participants in trial Randomised, double blind, placebo controlled. n=1,700; NSCLC; locally advanced, recurrent or metastatic; EGFR positive or negative. After 4 cycles of platinum-based Randomised, controlled. n=435 (planned); NSCLC; advanced (PS 0-1); not progressing on first line cisplatin- Randomised, double blind, placebo controlled. n=731; adults; NSCLC; stage IIIA-IIIB (PS 0 to 3); disease progression after one or two prior a 0 or 1 on the World Health Organisation performance status scale, or a Karnofsky score of

4 chemotherapy, eligible patients will be randomised to receive either erlotinib 150mg daily or placebo. gemcitabine. Randomised to maintenance with gemcitabine or erlotinib immediately after first line chemotherapy. Until disease progression or toxicity. PFS. chemotherapy regimens. Randomised to erlotinib or placebo maintenance. Follow-up Until disease progression, death or unacceptable toxicity. - Primary 25% increase in progression-free Response rate; median outcome survival (PFS) in unselected duration of response; PFS; patients; 30% increase in PFS in OS. EGFR positive patients. Secondary Overall survival (OS); time to OS; toxicity; quality of Toxicity. outcomes progression (TTP); objective life. response rate; duration of response; safety and tolerability; quality of life. PFS, OS and TTP from start of chemotherapy. Key results - - Response rate 8.9% with erlotinib and <1% with placebo (p=<0.001). Median duration of response 7.9 and 3.7 months respectively; PFS 2.2 and 1.8 months (hazard ratio 0.61, adjusted for stratification: p<0.001); OS 6.7 and 4.7 months respectively (hazard ratio 0.70 p<0.001) Expected reporting date Adverse effects - Study started June 2006; completion date unknown % of erlotinib group discontinued treatment due to adverse effects; 9% experienced moderate to severe rash. Estimated cost and cost impact The cost of erlotinib 150mg once a day for 30 days is 1,631. The cost for 4 months of treatment is 6, Potential or intended impact speculative Associated costs may include patient tumour biomarker testing. Patients Reduced morbidity Increased survival time Improved quality of life for patients and/or carers Quicker, earlier or more accurate diagnosis or identification of disease Other: None identified - 4

5 Services Increased use Service reorganisation required Staff or training required Decreased use Other: Delay need for secondline and palliative care None identified Costs Increased unit cost compared to alternative Increased costs: more patients coming for treatment Increased costs: capital investment needed New costs: Savings: Other: Delay need for second-line and palliative care References 1 National Institute for Health and Clinical Excellence. Erlotinib for the treatment of advanced non-small cell lung cancer. Technology Appraisal in development - publication expected November National Institute for Health and Clinical Excellence. Gefitinib for non-small cell lung cancer. 10 th wave. Technology Appraisal in development. Expected November National Institute for Health and Clinical Excellence. Cetuximab for advanced non-small cell lung cancer. Technology Appraisal in development. Expected date of use to be announced. 4 National Institute for Health and Clinical Excellence. Bevacizumab for the treatment of non-small cell lung cancer. Technology Appraisal terminated National Institute for Health and Clinical Excellence. Pemetrexed disodium for the treatment of mesothelioma. Technology appraisal 135. January 2008 (review expected September 2010). 6 National Institute for Health and Clinical Excellence. Pemetrexed for the treatment of non-small cell lung cancer. Technology Appraisal 124. August National Institute for Health and Clinical Excellence. Lung Cancer: The diagnosis and treatment of lung cancer. Clinical Guideline 24. February National Comprehensive Cancer Network (NCCN). Clinical practice guideline on non-small cell lung cancer, September Scottish Intercollegiate Guidelines Network (SIGN). Management of patients with lung cancer, Guideline 80, February European Society for Medical Oncology (ESMO). Minimum clinical recommendations for the diagnosis, treatment and follow-up of non-small cell lung cancer (NSCLC). Annals of Oncology 2005; 16 (1): Cancer Research UK, Cancer Stats Lung cancer and smoking UK, September Coleman M, Rachet B, Woods L et al. Trends in socio-economic inequalities in cancer survival in England and Wales up to British Journal of Cancer 2004; 90(7): EMedicine. Lung cancer: Non-small cell. Available at: (accessed ). 14 Liverpool Reviews and Implementation Group, ERG Report. Pemetrexed for the treatment of relapsed nonsmall cell lung cancer. National Institute for Clinical Excellence National Collaborating Centre for Acute Care. The diagnosis and treatment of lung cancer: methods, evidence and guidance. National Collaborating Centre for Acute Care Clinical Trials. NCT A study of Tarceva (erlotinib) following platinum-based chemotherapy in patients with advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC). Available at: (accessed ). 17 Clinical trials. NCT IFCT-GFPC A randomised phase III trial assessing in patients with advanced non-small cell lung cancer. Available at: (accessed ). 18 Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non-small cell lung cancer. New England Journal of Medicine. 2005; Jul 14: 353 (2): British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. Number 55. BMJ Publishing Group, London. March

6 The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)