Horizon Scanning Research September 2015 & Intelligence Centre

Dacomitinib for locally advanced or metastatic EGFR positive non- small cell lung cancer – first line

LAY SUMMARY

Lung cancer is often diagnosed at a late or advanced stage, when it This briefing is has already spread to other parts of the body. The life expectancy is based on information often less than a year. Non-small cell lung cancer is the most common available at the time type of lung cancer. of research and a limited literature Dacomitinib is a new drug being developed to treat patients with search. It is not advanced non-small cell lung cancer where the cancer cells have a intended to be a particular mutation (called EGFR positive). Dacomitinib is taken as a definitive statement tablet once a day. A study is currently looking to see how well on the safety, dacomitinib works in stopping non-small cell cancer from growing and efficacy or spreading, and how safe it is to take. effectiveness of the health technology If dacomitinib is licensed for use in the UK, it will offer an additional covered and should treatment option for patients with advanced EGFR positive non-small not be used for cell lung cancer and may improve survival. commercial purposes or commissioning NIHR HSRIC ID: 5620 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 Research & Intelligence Centre, University of Birmingham. Email: [email protected] Web: www.hsric.nihr.ac.uk Horizon Scanning Research & Intelligence Centre

TARGET GROUP

• Non-small cell lung cancer (NSCLC): advanced or metastatic; with epidermal growth factor receptor (EGFR) activating mutations – first line.

TECHNOLOGY

DESCRIPTION

Dacomitinib (PF-00299804) is a highly selective inhibitor of the pan-epidermal growth factor receptor (EGFR) family of tyrosine kinases (ErbB family). EGFRs play a major role in tumour cell proliferation and tumour vascularisation, and are often overexpressed or mutated in various tumour cell types. Dacomitinib specifically and irreversibly binds to and inhibits multiple EGFR subtypes, resulting in inhibition of proliferation and induction of apoptosis in EGFR-expressing tumour cells. Dacomitinib is administered orally at 45mg once daily until disease progression.

Dacomitinib does not currently have any Marketing Authorisation in the EU for any indication. Dacomitinib is also in phase II trials for glioblastoma, head and neck cancer, gastric cancer and brain metastases.

INNOVATION and/or ADVANTAGES

If licensed, dacomitinib will offer an additional treatment option for patients with advanced NSCLC.

DEVELOPER

Pfizer Limited.

AVAILABILITY, LAUNCH OR MARKETING

In phase III clinical trials.

PATIENT GROUP

BACKGROUND

Approximately 85-90% of all lung cancers are of the non-small cell type; NSCLC can be further classified into three histological sub-types, namely large-cell undifferentiated carcinoma, squamous cell carcinoma, and adenocarcinoma1. The symptoms of NSCLC include haemoptysis, malaise, significant weight loss, dyspnoea, and voice loss2. Smoking is the main cause of lung cancer, responsible for in excess of 80% of cases; other known risk factors include exposure to asbestos, arsenic, radon, and non-tobacco-related polycyclic aromatic hydrocarbons3. NSCLC has frequently metastasised by the time of diagnosis, resulting in a poor prognosis.

Horizon Scanning Research & Intelligence Centre

NHS or GOVERNMENT PRIORITY AREA

This topic is relevant to: • NHS England. 2013/14 NHS Standard Contract for Cancer: Chemotherapy (Adult). B15/S/a. • NHS England. 2013/14 NHS Standard Contract for Cancer: Chemotherapy (Children, Teenagers and Young Adults). B12/S/b. • NHS England. 2013/14 NHS Standard Contract for Cancer: Radiotherapy (All Ages). B01/S/a.

CLINICAL NEED and BURDEN OF DISEASE

Lung cancer is the second most common cancer in the UK, accounting for 13% of all new cases4. In England and Wales, there were 44,488 new diagnoses in 20124, and in 2013, 30,424 deaths from lung cancer were registered5. Around 85-90% of lung cancers are non- small cell6. Incidence of lung cancer is higher in lower socioeconomic groups, and survival is poorer in these groups compared to higher socioeconomic groups7. The majority of lung cancers are diagnosed in the later stages of the disease, with 21% presenting with locally and regionally advanced disease (stage IIIB) and 48% presenting with metastases (stage IV)2. Approximately 15% of NSCLC is evaluated as EGFR positive8. For people presenting with stage IIIB NSCLC the 5-year survival rate is around 7-9%; and for people presenting with stage IV NSCLC the 5-year survival rate varies from 2-13%2. Median survival for patients with stage IV NSCLC treated with platinum-based therapy is 8-12 months9,10.

In 2013-14, there were 88,350 hospital admissions in England due to lung cancer (ICD-10 C34), accounting for 108,216 finished consultant episodes and 282,717 bed days11. In 2013, there were 60,848 deaths from lung cancer registered in England and Wales12.

PATIENT PATHWAY

RELEVANT GUIDANCE

NICE Guidance

• NICE technology appraisal. Pemetrexed maintenance treatment following induction therapy with pemetrexed and cisplatin for non-squamous non-small-cell lung cancer (TA309). April 2014. • NICE technology appraisal. Erlotinib for the first-line treatment of locally advanced or metastatic EGFR-TK mutation-positive non-small-cell lung cancer (TA258). June 2012. • NICE technology appraisal. Erlotinib monotherapy for maintenance treatment of non- small-cell lung cancer (TA227). June 2011. • NICE technology appraisal. Gefitinib for the first-line treatment of locally advanced or metastatic non-small-cell lung cancer (TA192). July 2010. • NICE technology appraisal. Pemetrexed for the maintenance treatment of non-small-cell lung cancer (TA190). June 2010. • NICE technology appraisal. Pemetrexed for the first-line treatment of non-small-cell lung cancer (TA181). September 2009. • NICE technology appraisal. Erlotinib for the treatment of non-small-cell lung cancer (TA162). November 2008. • NICE technology appraisal. Pemetrexed for the treatment of non-small-cell lung cancer (TA124). August 2007. Horizon Scanning Research & Intelligence Centre

• NICE clinical guideline. Lung cancer: the diagnosis and treatment of lung cancer (CG121). April 2011. • NICE quality standard. Quality standard for lung cancer (QS17). March 2012.

Other Guidance

• European Society for Medical Oncology. Metastatic non-small cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. 20143. • Scottish Intercollegiate Guidelines Network. Management of lung cancer (137). 201413. • National Comprehensive Cancer Network. The NCCN clinical practice guidelines in oncology. Non-small cell lung cancer. 201314. • American College of Chest Physicians. Treatment of stage IV non-small cell lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. 201315. • American Society of Clinical Oncology. 2011 focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non- small cell lung cancer. 201116.

CURRENT TREATMENT OPTIONS

The aim of treatment for locally advanced or metastatic NSCLC is to prolong survival, improve quality of life, and control disease-related symptoms17. Treatment strategies should take into account the tumour histology and molecular pathology, as well as the patient’s age, performance status, comorbidities, and preferences3. Patients who smoke should be encouraged to cease, as cessation improves treatment outcomes3.

Current NICE guidelines recommend that chemotherapy is offered to patients with stage IV NSCLC and a good performance status (WHO 0 or 1 or a Karnofsky score of 80–100)18. Induction chemotherapy for advanced NSCLC should be a combination of a single third generation drug (docetaxel, gemcitabine, paclitaxel, or vinorelbine) plus a platinum drug (either carboplatin or cisplatin)18. Afatinib is an option, for epidermal growth factor receptor tyrosine kinase (EGFR-TK) positive metastatic NSCLC not previously treated with an EGFR- TK inhibitor19. Erlotinib and gefitinib are also options for patients with EGFR-TK positive metastatic NSCLC19.

EFFICACY and SAFETY

Trial ARCHER 1050, NCT01774721, NCT01858389, A7471047; dacomitinib; DP312804; dacomitinib vs gefitinib, phase II. phase III. Sponsor SFJ Pharmaceuticals Inc. Pfizer. Status Ongoing. Ongoing. 21 Source of Trial registry20. Trial registry . information Location EU (not UK), Japan, China and Korea. USA and Korea. Design Randomised, active controlled. Non-randomised, uncontrolled. Participants n=440; aged ≥18 years; evidence of n=35; aged 18 years and older; pathologically confirmed NSCLC with histologically confirmed, advanced EGFR activating mutation (exon 19 NSCLC; cohort A: T790M mutation of deletion or the L858R mutation in exon EGFR in exon 20, cohort B: all patients 21); no prior treatment with systematic irrespective of EGFR status, but therapy for NSCLC. excluding known T790M mutations. Horizon Scanning Research & Intelligence Centre

Schedule Randomised to dacomitinib 45mg oral, All participants receive dacomitinib 45mg once daily; or gefitinib 250mg oral, once oral every 12 hours on days 1-4 of the daily. first week, followed by 60mg every 12 hours on days 1-4 of each 2 week cycle thereafter. Follow-up Active treatment until disease 78 weeks follow up period. progression. Primary Progression free survival (PFS) at 18 Best overall response; objective response outcome/s months. rate. Secondary Overall survival (OS) and OS at 18 and Disease control rate; duration of outcome/s 30 months; patient reported outcomes of response, PFS. health related quality of life (HRQOL); European quality of life questionnaire (EQ-5D). Expected Study completion date reported as Study completion date reported as reporting February 2017. August 2015. date

ESTIMATED COST and IMPACT

COST

The cost of dacomitinib is not yet known.

IMPACT - SPECULATIVE

Impact on Patients and Carers

 Reduced mortality/increased length of survival  Reduced symptoms or disability

 Other  No impact identified

Impact on Health and Social Care Services

 Increased use of existing services  Decreased use of existing services

 Re-organisation of existing services  Need for new services

 Other:  None identified

Impact on Costs and Other Resource Use

 Increased drug treatment costs  Reduced drug treatment costs

 Other increase in costs:  Other reduction in costs:

 Other: uncertain unit cost compared to  None identified existing therapies.

Other Issues

 Clinical uncertainty or other research question  None identified identified:

Horizon Scanning Research & Intelligence Centre

REFERENCES

1 National Institute for Health and Care Excellence technology appraisal in development. Nintedanib for treating previously treated metastatic non-small cell lung cancer (ID438). Final scope. London: NICE; July 2014. 2 National Cancer Institute. General information about non-small cell lung cancer (NSCLC). www.cancer.gov/cancertopics/pdq/treatment/non-small-cell- lung/healthprofessional/page1#Section_48499. Accessed 11 August 2015. 3 Reck M, Popat S, Reinmuth N et al. Metastatic non-small cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2014;25(suppl 3):iii27-iii39. 4 Cancer Research UK. Lung cancer incidence statistics. www.cancerresearchuk.org/cancer- info/cancerstats/types/lung/incidence/ Accessed 12 August 2015. 5 Office for National Statistics. Mortality Statistics: Deaths Registered in England and Wales (Series DR) table 5, 2013. www.ons.gov.uk 6 American Cancer Society. Lung cancer (non-small cell). www.cancer.org/cancer/lungcancer-non- smallcell/detailedguide/non-small-cell-lung-cancer-what-is-non-small-cell-lung-cancer Accessed 12 August 2015. 7 Scottish Intercollegiate Guidelines Network (SIGN). Management of lung cancer (SIGN publication no. 137). Edinburgh: SIGN; February 2014. 8 National Institute of Health and Clinical Excellence. NICE technology appraisal costing statement. Erlotinib for the first-line treatment of locally advanced or metastatic EGFR-TK mutation-positive non-small-cell lung cancer. Technology appraisal TA258 London: NICE; June 2012. 9 Reinmuth N, Payer N, Muley T et al. Treatment and outcome of patients with metastatic NSCLC: a retrospective institution analysis of 493 patients. Respiratory Research 2013;14(1):139. 10 NIHR Horizon Scanning Centre. Ramucirumab (Cyramza) in combination with docetaxel for locally advanced or metastatic non-small cell lung cancer – second line. University of Birmingham, November 2014. www.hsc.nihr.ac.uk 11 Health and Social Care Information Centre. Hospital episode statistics for England. Inpatient statistics, 2013-14. www.hscic.gov.uk 12 Office for National Statistics. Deaths registered in England and Wales (series DR) - 2013. www.ons.gov.uk 13 Scottish Intercollegiate Guidelines Network. Management of lung cancer. National clinical guideline 137. Edinburgh: SIGN; February 2014. 14 National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Non-small cell lung cancer. Version 1. 2015. www.nccn.org/professionals/physician_gls/pdf/nscl.pdf 15 Socinski MA, Evans T, Gettinger S et al. Treatment of stage IV non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143suppl5:e341S-e368S. 16 Azzoli CG, Temin S, Aliff T et al. 2011 focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small cell lung cancer. Journal of Clinical Oncology 2011;29:3825-3831. 17 National Cancer Institute. Stage IV NSCLC Treatment. www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/healthprofessional/page11 Accessed 12 August 2015. 18 National Institute for Health and Clinical Excellence. Lung cancer: the diagnosis and treatment of lung cancer. Clinical guideline CG121. London: NICE; April 2011. 19 National Institute for Health and Care Excellence. NICE Pathways. Treatment for non-small cell lung cancer. www.pathways.nice.org.uk/pathways/lung-cancer Accessed 08 June 2015. 20 ClinicalTrials.gov. ARCHER 1050: A Randomized, Open Label Phase 3 Efficacy and Safety Study Of Dacomitinib (PF-00299804) Vs. Gefitinib For The First-Line Treatment Of Locally Advanced or Metastatic NSCLC In Subjects With EGFR Activating Mutations. clinicaltrials.gov/ct2/show/NCT01774721 Accessed 12 August 2015. 21 ClinicalTrials.gov. Phase 2 Open Label Trial Of Oral Intermittent Dacomitinib In Patients With Advanced NSCLC. clinicaltrials.gov/ct2/show/NCT01858389 Accessed 12 August 2015.