Non-small cell lung cancer (NSCLC) is the most

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1 Vol 3 April 2011 Clinical Pharmacist 109 First-line treatment for non-small cell lung cancer is surgery; but many patients are not suitable and, for these patients, management may involve radiotherapy, chemotherapy or newer targeted therapies Lung cancer treatment By Steve Williamson, MSc, MRPharmS, and Simon Purcell, DipClinPharm, MRPharmS SUMMARY Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. There have been a number of treatment developments for this condition in recent years so this article focuses mainly on the treatment of NSCLC. The treatment of small cell lung cancer is discussed in Box 1 (p110). Surgery Surgery provides the best chance of a cure for patients with stage I or stage II NSCLC. It involves removal of the tumour through resecting one or more lobes of the lung (lobectomy or bi-lobectomy) or through removal of the whole lung (pneumonectomy). The surgery is challenging and should only be undertaken in a unit with an appropriate level of expertise. The postoperative mortality rate is about 5% and patients can experience significant complications after surgery, including haemorrhage, Coloured chest X-ray showing lung cancer in frontal view Surgery provides the best chance of cure for patients with stage I and II non-small cell lung cancer (NSCLC). However, many patients with early NSCLC are not suitable for surgery and, for such patients, radiotherapy is the treatment of choice. First-line treatment of patients with advanced NSCLC is usually with a chemotherapy regimen that includes one platinum-based drug plus a third-generation medicine (eg, paclitaxel). In recent years the use of targeted treatments (eg, erlotinib or gefitinib) has improved outcomes for patients with advanced NSCLC. Simon Fraser Science Photo Library respiratory failure, infection and arrhythmias. 11 It is of vital importance, therefore, that patients are carefully selected and are fit for surgery. Assessment of a patient s performance status is mentioned in the accompanying article (p106). Pulmonary function tests are also routinely carried out before both surgery and radical radiotherapy. 12 Increasingly, adjuvant chemotherapy is being given after surgery to improve survival. Cisplatin plus vinorelbine is the most commonly used regimen and has been shown to increase median survival. In one study patients who were given the combination had a median This is one of two CL NICAL FOCUS articles in this issue of Clinical Pharmacist that are linked to a Centre for Pharmacy Postgraduate Education learning@lunch flex module on lung cancer designed for hospital pharmacists and technicians in England. You can use these articles to provide key background knowledge on the topic before participating in a learning@lunch flex session at your hospital. The module contains reflective questions, case studies and practice activities to allow you to put your learning into action. You can order copies of this module via your CPPE key contact at the hospital or by ing Jayne Plant on jayne@cppe.ac.uk. Find out more at

2 110Clinical Pharmacist April 2011 Vol 3 Box 1: Treatment of small cell lung cancer Although non-small cell lung cancer management has benefited from the development of targeted therapies, small cell lung cancer (SCLC) is still treated with traditional cytotoxic chemotherapy combination regimens. SCLC is very aggressive and has nearly always metastasised by the time of diagnosis; this means treatment will be palliative and not curative. Nevertheless, chemotherapy can initially achieve good responses. Regimens The table (inset) summarises the commonly used chemotherapy regimens for small cell lung cancers. Combination regimens such as CAV, EP, and CE can produce initial response rates of 80%. 1 The cyclophosphamide-based regimens (eg, CAV) were the traditional regimens of choice but have now been superseded by etoposide and platinum-based drug combinations, which have the benefit of reduced myelosuppression. One of the biggest comparative trials showed that EP (versus cyclophosphamide plus epirubicin and vincristine) gave a superior median survival (14.5 versus 9.7 months), with a five-year survival of 10% versus 3% for limited-stage disease. 2 Experience with the UK standard carboplatin-based regimen CE, which is essentially a modification of EP, suggests it is as effective. Carboplatin is less toxic and easier to administer, which is important when treatment is palliative, and the clinician needs to balance the benefits of treatment with the effects of toxicity on the quality of life of patients. Until recently there had been little progress in chemotherapy for SCLC, but there is now interest around the use of the camptothecin derivatives topotecan and irinotecan, which have shown promising activity. Topotecan was recently granted a UK licence as monotherapy for the treatment of adult patients with relapsed SCLC. A randomised, phase III study in 211 patients with relapsed SCLC showed IV topotecan to be at least as effective as CAV (median survival 25 versus 24.7 weeks) but with the advantage of improved control of several disease-related symptoms and fewer dose reductions for non-haematological toxicity, particularly neurotoxicity. 3 Further randomised studies have shown that oral and IV topotecan have similar efficacy. 4,5 In a randomised, phase III study of 141 relapsed SCLC patients considered unsuitable for further IV chemotherapy, oral topotecan added to best supportive care (BSC) significantly extended median survival compared with BSC alone (25.9 versus 13.9 weeks). 6 Relapse In the treatment of SCLC, most patients experience a good initial response with stabilisation of disease and palliation of symptoms, but patients will invariably relapse at some point. Patients who have had at least six months of stable disease Chemotherapy regimens for SCLC REGIMEN NAME DRUG DOSING PER CYCLE COMMENTS EP 7 Cisplatin IV 60 80mg/m 2 day 1 Etoposide IV 115mg/m 2 days 3 5 CE 8 Carboplatin IV 5 area under curve (AUC) day 1 Etoposide IV 120mg/m 2 day 1 Etoposide oral 240mg/m 2 days 2 3 CAV 9 Cyclophosphamide IV 750mg/m 2 day 1 Doxorubicin IV 50mg/m 2 day 1 Vincristine IV 1.2mg/m 2 (maximum 2mg) day 1 Topotecan 3 Topotecan oral 2.3mg/m 2 /day for five days every 21 days (for four cycles) will often be retreated with the same chemotherapy regimen used first line. If the relapse is earlier than six months a second-line regimen (eg, topotecan) may be tried or they will receive BSC (ie, treatment to support and control the symptoms but not actually treat the cancer). Radiotherapy Radiotherapy is used to treat SCLC, particularly thoracic and cranial metastases, because it has been shown to improve disease control and have a survival benefit when compared with chemotherapy alone. Paraneoplastic syndromes Patients with SCLC are also particularly prone to paraneoplastic syndromes, which are defined as hormonal, neurological, haematological and other clinical and biochemical disturbances associated with the cancer but not directly related to invasion by the primary tumour or its metastases. Cisplatin is effective but highly toxic and requires prolonged administration with IV fluid support to avoid renal toxicity. Nausea is particularly bad with cisplatin. May be given with concurrent radiation Carboplatin is substituted for cisplatin to produce a better tolerated regimen. A variety of slightly different etoposide dose schedules are used Now most commonly used as secondline therapy Oral option, approved by NICE in November for use if retreatment with the first-line regimen is not considered appropriate and the CAV regimen is contraindicated survival of 65.7 months compared with 43.7 months for patients who were not given adjuvant chemotherapy, giving a 8.6% improvement in overall survival at five years. 13 Radiotherapy Radiotherapy with curative intent is the choice for patients with stage I to III NSCLC who are not suitable for surgery. Traditionally the total radiotherapy dose is calculated and the dose is then divided into smaller portions known as fractions. These fractions are given once daily over three to four weeks. Recent research has focused on delivering the fractions more quickly in a schedule known as CHART (continuous, hyperfractionated, accelerated radiotherapy), with smaller doses of radiation given three times a day over 12 consecutive days. CHART has a small but significant survival advantage over traditional radiotherapy but has proven difficult to adopt in some European countries due to constraints on services, such as the availability of the linear accelerators required and the staff who operate them. Chemotherapy Platinum-based chemotherapy combinations are the standard first-line treatment for advanced NSCLC. The National Institute for Health and Clinical Excellence recommends using a combination of a single thirdgeneration medicine (eg, vinorelbine, gemcitabine or

3 Vol 3 April 2011 Clinical Pharmacist 111 Radiotherapy can be used to treat stage I to III non-small cell lung cancer docetaxel) plus a platinum-based drug (carboplatin or cisplatin). 11 The choice of the combination will vary according to the preferences of the clinician and the treating centre. Details of commonly used regimens are outlined in Box 2. The regimens are usually given for four cycles unless there is evidence that a patient s disease has progressed, in which case the regimen will be stopped. Recently a large trial of a first-line combination of pemetrexed plus cisplatin was shown to offer a significantly longer survival than gemcitabine plus cisplatin (median of 12.6 months compared with 10.9 months) in patients with adenocarcinoma of the lung. 19 This was the first time a difference had been shown in response to NSCLC chemotherapy depending on the disease histology. This led to a change in the licence of pemetrexed to reflect the higher activity in patients with non-squamous NSCLC. Pemetrexed is administered at a dose of 500mg/m 2 every three weeks. Although chemotherapy can improve symptoms survival benefit is modest. The response rate is around 30 40% and the median survival is around 10 months. 20 For patients who are less fit and considered unable to tolerate combination chemotherapy, single agent gemcitabine (1,200 1,250mg/m 2 ) or oral vinorelbine (60 80mg/m 2 ) can be used. If a patient s disease progresses despite first-line treatment, he or she is assessed for suitability of second-line treatment with docetaxel or pemetrexed monotherapy. The TAX317 study of docetaxel versus best supportive care (BSC) showed a clear survival benefit with docetaxel (75mg/m 2 ) the one-year survival rate was 37% for docetaxel versus 11% for BSC. 21 However, the response rate was low (7%) and a large proportion of patients experienced moderate-to-severe neutropenia with docetaxel. Pemetrexed has been shown to have similar efficacy to that of second-line docetaxel. 22 Pemetrexed exhibits a slightly more favourable toxicity profile than docetaxel, but is more expensive. P Marazzi Science Photo Library principle, toxic therapy is not acceptable if prolongation of survival and palliation of symptoms is unlikely. Patients receiving chemotherapy must be monitored and counselled on the risks of bone marrow suppression and neutropenia. Patients must be warned that if they develop a febrile illness, or are feeling unwell with symptoms of infection, they immediately require their full blood count and neutrophil count to be checked by their GP, hospital emergency department or oncology ward. See Box 3 (p113) for an outline of some of the supportive therapies used. Targeted therapies Erlotinib Erlotinib was the first targeted therapy to have a significant impact in NSCLC. It is a small molecule inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. EGFR is part of the control mechanism of cell growth that is fundamentally deranged in cancer. EGFR overproduction is common in NSCLC and is associated with aggressive tumour cell biology, chemotherapy resistance and reduced survival. Second- or third-line erlotinib was shown in the BR21 study 23 to have a survival benefit comparable to that of docetaxel in the TAX317 study, 21 but without the neutropenia and myelotoxicity associated with chemotherapy. Erlotinib was administered as a 150mg once-daily dose given until disease progression. In the BR21 study median overall survival was 4.7 months in the placebo arm compared with 6.7 months in the erlotinib arm. The percentage of patients surviving at 12 months was 22% and 31%, respectively. This two-month increase Box 2: Combination chemotherapy for NSCLC The following are options for first-line intravenous chemotherapy treatment of advanced non-small cell lung cancer: Gemcitabine plus carboplatin (21-day cycle) 14 Gemcitabine 1,250mg/m 2 on day 1 and day 8 Carboplatin 5 AUC on day 1 Paclitaxel plus carboplatin (21-day cycle) 15 Paclitaxel 175mg/m 2 on day 1 Carboplatin 5 AUC on day 1 Paclitaxel plus cisplatin (21-day cycle) 16 Paclitaxel 175mg/m 2 on day 1 Cisplatin 70mg/m 2 on day 1 Vinorelbine plus cisplatin (21-day cycle) 17 Vinorelbine 25 30mg/m 2 (maximum 60mg) on day 1 and day 8 Cisplatin 60 80mg/m 2 on day 1 Docetaxel plus cisplatin (21-day cycle) 18 Toxicity Management of side effects of chemotherapy is important; clinicians treating lung cancer must ensure there is a balance between toxicity and benefit. In Docetaxel 75mg/m 2 on day 1 Cisplatin 75mg/m 2 on day 1

4 112Clinical Pharmacist April 2011 Vol 3 in survival could be considered modest, but there are many anecdotal examples of a small proportion of patients having a significant and prolonged response. The advantage of a targeted therapy in these cases is that, unlike traditional chemotherapy with cumulative bone marrow toxicity, some patients can continue to take erlotinib for a long period. Erlotinib is not free from toxicity the adverse effect profile of the EGFR inhibitors is different from traditional chemotherapy with patients prone to diarrhoea and severe skin reactions. Early results from a study on the use of erlotinib for patients with EGFR mutations are promising. The OPTIMAL study 24 compared first-line erlotinib with combination chemotherapy using gemcitabine and carboplatin. Preliminary findings show a response rate of about 84% with erlotinib versus about 37% with chemotherapy. The progression-free survival with erlotinib was reported to be 13.1 months, compared with 4.6 months for chemotherapy. 24 The full trial results are needed to confirm these findings. Gefitinib Gefitinib is another EGFR inhibitor that has been under investigation for several years, but early trials yielded poor results, which slowed the development of the drug. More recently, when used in trials that specifically identified patients with EGFR-TK mutations, the benefit of gefitinib has become clear. The Iressa pan-asia study (IPASS) 25 investigated patients with lung adenocarcinoma who had never smoked or were very light smokers. The trial showed that, in the subgroup of patients with an EGFR-TK mutation, the median progression-free survival with gefitinib was 9.5 months versus 6.3 months for those treated with paclitaxel plus carboplatin. The objective Continued on p113 In calcium and vitamin D3 supplementation?do you have a portfolio documenting your professional development 3 Choices Lemon, Dissolve and Tutti Frutti 2 Presentations Chewable and Effervescent tablets 1 Dose 1,200mg calcium and 800 IU vitamin D3 Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to ProStrakan Ltd on Refer to the Summary of Product Characteristics before prescribing, particularly in relation to side-effects, precautions and contraindications. Adcal-D3, Adcal-D3 Lemon and Adcal-D3 Dissolve are used as an adjunct to specific therapy for osteoporosis and in situations requiring therapeutic supplementation of malnutrition. Legal category: P. Further information is available on request from the Marketing Authorisation Holder: ProStrakan Ltd Galabank Business Park, Galashiels, Scotland TD1 1QH. Alternatively, it may be found in the Summary of Product Characteristics. Adcal-D3 is a registered trademark of ProStrakan Ltd. Date of preparation: January Code: M001/1382 CAREER DEVELOPMENT (p119)

5 Vol 3 April 2011 Clinical Pharmacist 113 Continued from p112 tumour response rate was higher for gefitinib (71.2% versus 47.3%). However, there was no statistically significant difference in the estimates of overall survival between groups and gefitinib was shown to be inferior, compared with carboplatin plus gemcitabine, for patients without the EGFR-TK mutation. There has been some debate over the applicability of the IPASS trial to a western population since the evidence for clinical effectiveness was derived mainly from a trial of gefitinib in east-asian women who were non-smokers and had tumours with adenocarcinoma histology. Nonetheless, it is likely that the efficacy of gefitinib depends on the EGFR-TK mutation status of the patient, and that EGFR- TK mutation-positive patients are likely to respond to gefitinib irrespective of their gender, ethnicity, smoking status or the histology of their tumour. Bevacizumab Another targeted therapy is bevacizumab, which is licensed to be given in addition to platinum-based chemotherapy for the first-line treatment of patients with locally advanced metastatic or recurrent non-squamous NSCLC. Data from two large studies (ECOG 4599 and AVAiL) 26,27 showed a small survival advantage when bevacizumab was added to standard combination chemotherapy. The ECOG study showed a median overall survival of 12.3 months in patients taking bevacizumab plus paclitaxel and carboplatin compared with 10.3 months for chemotherapy alone. 26 However, the AVAiL study showed no overall survival benefit with the addition of bevacizumab to gemcitabine and cisplatin therapy, despite improvement in progression-free survival. The mixed trial results, high cost and concerns over pulmonary haemorrhage caused by bevacizumab are barriers to its use. 27 Maintenance treatment The role of erlotinib in the management of NSCLC has expanded to include maintenance treatment after first-line chemotherapy. In the SATURN study, erlotinib was given to patients with locally advanced or metastatic NSCLC who did not progress immediately after four cycles of platinum-based double chemotherapy. 28 Erlotinib demonstrated improved mean progression-free survival (22.4 weeks compared with 16.0 weeks for placebo) and median overall survival. Quality of life was no worse for patients treated with erlotinib than for those in the placebo group, although it could be argued that patients need to be relatively fit and have good performance status for maintenance therapy to be considered. Pemetrexed has also shown benefit as maintenance therapy for patients with non-squamous NSCLC. One study demonstrated an overall survival for patients with NSCLC receiving pemetrexed maintenance treatment of 15.5 months compared with 10.3 months for patients receiving placebo. 29 Adverse events with pemetrexed include fatigue, nausea, loss of appetite, tingling or numbness in the hands and feet, and skin rash. Monitoring patients on oral treatment Erlotinib and gefitinib are oral medicines that are taken continuously until a patient s disease progresses. They have the advantage of not causing myelosuppression and, therefore, regular monitoring for this is not required. However, other significant side effects need to be managed 75% of patients taking erlotinib develop a rash and over 50% experience diarrhoea. 30 The toxicities seen with these oral agents are often idiopathic and so it is vital that patients receive appropriate information and counselling on how to take their medicines, the likely side effects and whom to contact in the case of any problems. Most cancer centres operate a 24-hour helpline or triage service for patients. Many specialist oncology pharmacists have expanded their role into chemotherapy counselling and toxicity management clinics. There is a current trend in oncology for chemotherapy to be delivered closer to patients homes and scoping exercises are being undertaken to assess the feasibility of community pharmacies dispensing oral anticancer treatments (some already do so for private prescriptions). The responsibilities of pharmacists in ensuring safe and effective use of oral anticancer treatments are almost certainly going to develop further. The future There are many new treatment options for NSCLC in development. At the European Society of Medical Oncology conference, held in Milan, Italy, in October 2010, the first evidence of use of the next generation of TK inhibitors was presented. Afatinib irreversibly inhibits EGFR-TK and has activity against EGFR mutations not sensitive to erlotinib or gefitinib. The placebo-controlled LUX-Lung 1 study 31 sought to establish the role of afatinib Box 3: Supportive therapies Adverse effects associated with the treatment of lung cancer will often need to be managed using supportive therapies as described below. Antiemetics Cisplatin-based chemotherapy is highly emetogenic and can cause delayed nausea and vomiting (24 hours after chemotherapy), which can be difficult to treat. 5-HT 3 antagonists (eg, ondansetron or granisetron) can be used in conjunction with dexamethasone to prevent chemotherapyinduced nausea and vomiting. Newer medicines, such as aprepitant a neurokinin-1 receptor antagonist have been shown to reduce the incidence of acute and delayed nausea and vomiting associated with cisplatin-based regimens. Analgesics Patients with lung cancer will typically present with some degree of chest, shoulder or back pain. Treatment should follow the World Health Organization s pain ladder. Renal function must be monitored closely and caution exercised when using non-steroidal anti-inflammatory drugs for patients being treated with pemetrexed or cisplatin. Granulocyte-colony stimulating factor Recombinant human granulocyte-colony stimulating factor (GCSF) is occasionally used to prevent neutropenia in an episode of neutropenic sepsis following adjuvant chemotherapy. However, because the treatment intent for most lung cancers is palliative, dose-reduction of chemotherapy is the preferred strategy in most cancer centres for the management of neutropenia. Creams Skin toxicity (typically a papulopustular, follicular, acneiform rash) is a common side effect of the newer EGFR-TK inhibitors erlotinib and gefitinib. Preventive treatment with emollients (such as aqueous cream) is often advised followed by treatment with topical or systemic corticosteroids and antibacterials if skin rash becomes more severe.

6 114Clinical Pharmacist April 2011 Vol 3 for patients who had failed a first-line EGFR-TK inhibitor. The study reported a 7% response rate in the patients receiving afatinib and a progression-free survival of 3.3 months compared with 1.1 months for placebo. However, there was no difference in overall survival found, which may have been due to placebo patients in the trial crossing over to active treatment. More data are needed to establish the role of this potential therapy. References 1 DeVita VT, Lawrence TS, Rosenberg SA, et al. DeVita, Hellman, and Rosenberg s Cancer: Principles and Practice of Oncology. 8th Edition. Philadelphia: Lippincott Williams and Wilkins; Sundstrom S, Bremnes RM, Kaasa S, et al. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years follow-up. Journal of Clinical Oncology 2002;20: Von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin and vincristine for the treatment of recurrent small-cell lung cancer. Journal of Clinical Oncology 1999;17: Von Pawel J, Gatzemeier U, Pujol JL, et al. Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small cell lung cancer. Journal of Clinical Oncology 2001;19: Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in relapsed small cell lung cancer. Journal of Clinical Oncology 2007;25: O Brien ME, Tudor-Eliade C, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. Journal of Clinical Oncology 2006;24: Evans WK, Osoba D, Feld R, et al. Etoposide (VP-16) and cisplatin: An effective treatment for relapse in small-cell lung cancer. Journal of Clinical Oncology 1985;3: Smith IE, Evans BD, Gore ME, et al. Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer. Journal of Clinical Oncology 1987;5: Sculier JP, Klastersky J, Libert P, et al: A phase II study evaluating CAV (cyclophosphamide, adriamycin, vincristine) potentiated or not by amphotericin B entrapped into sonicated liposomes, as salvage therapy for small-cell lung cancer. Lung Cancer 1990;6: National Institute for Health and Clinical Excellence. Topotecan for the treatment of relapsed small-cell lung cancer. November (accessed 5 January 2011). 11 National Institute for Health and Clinical Excellence. The diagnosis and treatment of lung cancer. February (accessed 5 January 2011). 12 Cancer Therapy Evaluation Program. Common terminology criteria for adverse events, version 3.0. August (accessed 5 January 2011). 13 Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncology 2006;7: Rudd RM, Gower NH, Spiro SG, et al. Gemcitabine plus carboplatin versus mitomycin, ifosfamide and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group. Journal of Clinical Oncology 2005;23: Kelly K, Crowley J, Bunn P, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: A Southwest Oncology Group trial. Journal of Clinical Oncology 2001;19: Bonomi P, Kim K, Fairdough D, et al. Comparison of survival and quality of life in advanced NSCLC patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin. Journal of Clinical Oncology 2000;18: Le Chevalier T, Brisgand D, Douillard JY, et al. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. Journal of Clinical Oncology 1994;12: Steve Williamson is a consultant pharmacist for cancer services at Northumbria Healthcare NHS Trust and North of England Cancer Network and Simon Purcell is a specialist oncology pharmacist and teacher practitioner at Clatterbridge Centre for Oncology NHS Foundation Trust. E: steve.williamson@nhct.nhs.uk 18 Fossella F, Pereira Jose R, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. Journal of Clinical Oncology 2003;21: Scagliotti V, Parikh P, Von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. Journal of Clinical Oncology 2008;26: Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. New England Journal of Medicine 2002;346: Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomised trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum based chemotherapy. Journal of Clinical Oncology 2000;18: Hanna N, Shepherd FA, Fossella FV, et al. Randomised phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. Journal of Clinical Oncology 2004;22: Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. New England Journal of Medicine 2005;353: Zhou C, Wu YL, Chen G, et al. Efficacy results from the randomized phase III OPTIMAL (CTONG 0802) study comparing first-line erlotinib versus carboplatin (CBDCA) plus gemcitabine (GEM) in Chinese advanced non-small-cell lung cancer (NSCLC) patients (PTS) with EGFR activating mutations. 35th European Society of Medical Oncologists Congress. Milan, Italy. October Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin paclitaxel in pulmonary adenocarcinoma. New England Journal of Medicine 2009;361: Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. New England Journal of Medicine 2006;355: Reck M, Von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non small-cell lung cancer: AVAiL. Journal of Clinical Oncology 2009:27; Cappuzzo F, Ciuleanu TS, Stelmakh l, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncology 2010;11: Ciuleanu T, Brodowicz T, Zielinski C, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for nonsmall-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009;374: Roche Products Limited. Summary Of Product Characteristics: Tarceva. September (accessed 5 January 2011). 31 Miller VA, Hirsh V, Cadranel J, et al. A phase IIB/III double-blind randomized trial of afatinib (BIBW2992, an irreversible inhibitor of EGFR/HER1 and HER2) + best supportive care (BSC) versus placebo + BSC in patients with NSCLC failing 1 2 lines of chemotherapy and erlotinib or gefitinib (LUX-LUNG 1). 35th European Society of Medical Oncologists Congress. Milan, Italy. October Now put your learning into practice by joining colleagues at a CPPE learning@lunch flex session in your hospital. During the session you will test your knowledge with five reflective questions and three true-to-life case studies. You will discuss the most appropriate treatment strategies for lung cancer while focusing on the emergency admission of Mrs Brown. Our other case studies will explore the place of erlotinib in therapy and the management of chemotherapy-induced nausea and vomiting. For more information about taking part in a learning@lunch flex session or setting up your own learning community, turn to the contact details on p109.