Tarceva Italian Lung Optimization tRial

Non Small Cell Lung Cancer (NSCLC) Clinical Trial

— TAILOR  

Official title:

Optimization of Erlotinib for the Treatment of Patients With Advanced Non Small Cell Lung Cancer: an Italian Randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00637910
• Other study ID #: FARM6F5JER
• Secondary ID: 2007-004786-17
• Status: Recruiting
• Phase: Phase 3
• First received: March 12, 2008
• Last updated: February 23, 2012
• Start date: November 2007
• Est. completion date: February 2013

Study information

• Verified date: February 2012
• Source: Fatebenefratelli and Ophthalmic Hospital
• Contact: Marina C Garassino, MD
• Phone: +39 0263632223
• Email: marina.garassino[@]fbf.milano.it
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: Ministry of HealthItaly: National Bioethics CommitteeItaly: National Institute of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to assess the superiority of docetaxel in comparison to erlotinib in second line in wild-type EGFR tumour patients.

Description:

Erlotinib is registered in all patients affected with NSCLC in second and subsequent lines with a small benefit on Overall Survival. Recent evidence suggest that patients with EGFR mutations have a clear benefit when they are treated with EGFR tyrosine kinase inhibitors, while the role of these drugs in wild-type EGFR patients, that are representing the large majority (about 85-90%), is still unclear and no properly planned trials assessed before this issue. Recently, indirect evidence on subgroup analyses on randomized trial suggest that chemotherapy might be superior to erlotinib in wild-type EGFR patients.

Moreover, several authors do not recommend the use of EGFR determined with immunohistochemistry (IHC) or FISH because they do not reproducibly predict outcome.

For these reasons the protocol was amended in May 2011 in a superiority trial of docetaxel versus erlotinib, while the first version was aimed to assess the interaction with biomarkers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 850
• Est. completion date: February 2013
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or older

• Histological or cytological confirmation of NSCLC (may be from initial diagnosis of NSCLC or subsequent biopsy). Only patients with available tissue samples may be included in the study

• Absence of EGFR mutations of exons 19 or 21 (randomization)

• Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy

• One prior platinum-based at adequate doses and taxane free regimen

• Measurable (uni-dimensional) disease by RECIST in a lesion not previously irradiated or non-measurable disease

• ECOG-PS 0-2

• ANC greater than 1.5 x 109/L and platelets greater than 100 x 109/L

• Bilirubin level either normal or <1.5xULN

• AST (SGOT) and ALT (SGPT) <2.5xULN (=5 x ULN if liver metastases are present)

• Serum creatinine <1.5xULN

• Effective contraception for both, male and female pts, if the risk of conception exists

• Recovery from all acute toxicities of prior therapies

• Provision of written informed consent to the analysis of biological markers (registration)

• Provision of written informed consent to enter the randomized part of the study (randomization)

Exclusion Criteria:

• Prior therapy with an experimental agent whose primary mechanism of action is inhibition of EGFR or its associated tyrosine kinase

• Prior chemotherapy with taxanes

• Newly diagnosed CNS metastases that have not yet been treated with surgery and/or radiation. Pts with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they have evidence of clinically SD (no steroid therapy or steroid dose being tapered) for at least 28 daysLess than 14 days since completion of prior radiotherapy or persistence of any radiotherapy related toxicity

• Any unresolved chronic toxicity from previous anticancer therapy that, in the opinion of the investigator, makes it inappropriate for the patient to be enrolled in the study Known severe hypersensitivity to erlotinib or any of the excipients of this product

• Known hypersensitivity to docetaxel, polysorbate 80 or other drugs formulated with polysorbate 80, or any of the excipients of docetaxel

• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ

• Unable to swallow tablets

• Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic or patients with uncomplicated progressive lymphangitic carcinomatosis need not be excluded)

• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease)

• As judged by the investigator, any inflammatory changes of the surface of the eye

• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Erlotinib
Erlotinib 150 mg/day per os until disease progression or unacceptable toxicity develops
• Docetaxel
Docetaxel 75 mg/mq on day 1, every 21 days (3-weekly schedule) or Docetaxel 35 mg/mq 0n day 1,8 and 15 every 28 days (weekly schedule). _Until disease progression or unacceptable toxicity develops

Locations

Country	Name	City	State
Italy	S. Giovanni di Dio Hospital	Agrigento
Italy	Pesenti-Fenaroli Hospital	Alzano Lombardo	Bergamo
Italy	Ospedale San Donato	Arezzo
Italy	Oncologia A.S.L. AV1	Ariano Irpino	Avellino
Italy	Centro di Riferimento Oncologico	Aviano	Pordenone
Italy	Azienda Ospedaliera Universitaria Consorziale Policlinico	Bari
Italy	Fatebenefratelli Hospital	Benevento
Italy	G. Rummo Hospital	Benevento
Italy	Ospedali Riuniti	Bergamo
Italy	Ospedale centrale di Bolzano	Bolzano	BZ
Italy	Oncologia Medica Azienda Spedali Civili	Brescia	BS
Italy	Pneumologia Azienda Spedali Civili	Brescia	BS
Italy	Armando Businco Oncological Hospital	Cagliari
Italy	Ospedale S. Elia	Caltanissetta	CL
Italy	Presidio Ospedaliero Cardarelli ASL 3	Campobasso
Italy	Ospedale Civile di Casalpusterlengo	Casalpusterlengo	Lodi
Italy	Ospedale Civile Ferrari	Casarano	Lecce
Italy	Multimedia Santa Maria	Castellanza	Varese
Italy	Sant'Anna Hospital	Como
Italy	S. Sebastiano Hospital	Correggio	Reggio Emilia
Italy	Mariano Santo Hospital	Cosenza
Italy	Ospedale Maggiore di Crema	Crema
Italy	S. Croce e Carle Hospital	Cuneo
Italy	Istituto Toscano Tumori Ospedale S. Giuseppe Antica Sede	Empoli	Firenze
Italy	Fabriano Hospital	Fabriano	Ancona
Italy	A.O.U. S. Anna	Ferrara
Italy	A.O.U. Careggi	Firenze
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	A.O. San Martino	Genova
Italy	Galliera Hospital	Genova
Italy	Azienda Ospedaliera Melegnano- P.O. Gorgonzola	Gorgonzola	Milano
Italy	San Leonardo Hospital	Gragnano	Napoli
Italy	Ospedale Santa Barbara	Iglesias	Carbonia Iglesias
Italy	F. Veneziale Hospital	Isernia
Italy	Renzetti Hospital	Lanciano	Chieti
Italy	Ospedale S. Maria Goretti	Latina	LT
Italy	Azienda Ospedaliera di Lecco	Lecco
Italy	Ospedale Mater Salutis	Legnago	Verona
Italy	Legnano Hospital	Legnano	Milano
Italy	Umberto I Hospital	Lugo	Ravenna
Italy	Ospedale Civile di Legnano -Presidio di Magenta	Magenta	Milano
Italy	Umberto I Hospital	Mestre	Venezia
Italy	Azienda Ospedaliera Luigi Sacco Polo Universitario	Milano
Italy	Fatebenefratelli and Ophthalmic Hospital	Milano
Italy	Fondazione Ospedale Maggiore Policlinico - Mangiagalli e Regina Elena	Milano
Italy	San Carlo Borromeo Hospital	Milano
Italy	San Paolo Hospital	Milano
Italy	Monfalcone Hospital	Monfalcone	Gorizia
Italy	Policlinico Universitario di Monserrato	Monserrato	Cagliari
Italy	Ospedale Valdichiana "Nottola"	Montepulciano	Siena
Italy	San Gerardo Hospital	Monza	Milano
Italy	A.O. Monaldi	Napoli
Italy	Cardarelli Hospital	Napoli
Italy	D. Cotugno Hospital	Napoli
Italy	San Gennaro Hospital - ASL NA 1	Napoli
Italy	ASL SA1 -P.O. Umberto I	Nocera Inferiore	Salerno
Italy	Ospedale Maggiore della Carità	Novara
Italy	Azienda Ospedaliera Universitaria Presidio "Paolo Giaccone"	Palermo
Italy	Centro Oncologico "La Maddalena"	Palermo
Italy	Policlinico Universitario Palermo	Palermo	PA
Italy	Presidio Ospedaliero "M. Ascoli" ARNAS Civico	Palermo
Italy	San Francesco Hospital	Paola	Cosenza
Italy	San Massimo Hospital	Penne	Pescara
Italy	S. Maria della Misericordia Hospital	Perugia
Italy	Piacenza Hospital	Piacenza
Italy	Ospedale Valdelsa "Campostaggia"	Poggibonsi	Siena
Italy	S. Maria degli Angeli Hospital	Pordenone
Italy	Ospedale Civile Santa Maria delle Croci	Ravenna
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	Rho Hospital - Azienda Ospedaliera Salvini-Garbagnate	Rho	Milano
Italy	Oncologia Medica-San Camillo Forlanini Hopsital	Roma
Italy	Ospedale San Pietro Fatebenefratelli	Roma
Italy	Pneumologia Oncologica II-San Camillo Forlanini Hospital	Roma
Italy	Policlinico Umberto I	Roma
Italy	Policlinico Umberto I	Roma
Italy	S. Giovanni - Addolorata Hospital	Roma
Italy	Università Campus Bio-Medico	Roma
Italy	Azienda Ospedaliera S. Giovanni di Dio e Ruggi d'Aragona	Salerno
Italy	Ospedale Civile di Saluzzo Savigliano	Saluzzo	Cuneo
Italy	Policlinico San Donato	San Donato Milanese	Milano
Italy	B. Eustachio Hospital	San Severino Marche	Macerata
Italy	Azienda Ospedaliera Busto Arsizio	Saronno	Varese
Italy	Ospedale Civile SS. Annunziata	Sassari
Italy	Universita' di Sassari Oncologia Medica	Sassari
Italy	Ospedale di Scandiano	Scandiano	Reggio Emilia
Italy	Ospedale Civili Riuniti Giovanni Paolo II	Sciacca	Agrigento
Italy	IRCCS Multimedica	Sesto San Giovanni	Milano
Italy	Ospedale Civile di Siderno - ASL n°9 Locri	Siderno	Reggio Calabria
Italy	Ospedale Morelli	Sondrio
Italy	Sondrio Hospital-Azienda Ospedaliera Valtellina e Valchiavenna	Sondrio
Italy	San Vincenzo Hospital	Taormina	Messina
Italy	Ospedale di Terni	Terni	TR
Italy	S. Giovanni Evangelista Hospital	Tivoli	Roma
Italy	A.O.U. San Giovanni Battista Molinette	Torino
Italy	Ospedali Riuniti Umberto I - Lancisi - Salesi	Torrette	Ancona
Italy	Presidio Ospedaliero San Luca	Vallo della Lucania	Salerno
Italy	Ospedale di Circolo	Varese
Italy	SS. Giovanni e Paolo Hospital	Venezia
Italy	Ospedale Policlinico G.B. Rossi	Verona	VR
Italy	San Bartolo Hospital	Vicenza
Italy	Ospedale Civile Vigevano	Vigevano	Pavia
Italy	Ospedale Civile di Vimercate	Vimercate	Milano
Italy	Ospedale di Vipiteno	Vipiteno	Bolzano
Italy	Belcolle Hospital	Viterbo
Italy	Vizzolo Predabissi Hospital	Vizzolo Predabissi	Milano

Sponsors (3)

Lead Sponsor	Collaborator
Fatebenefratelli and Ophthalmic Hospital	Mario Negri Institute for Pharmacological Research, Niguarda Hospital

Country where clinical trial is conducted

Italy, 

References & Publications (31)

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Douillard JY, Shepherd FA, Hirsh V, Mok T, Socinski MA, Gervais R, Liao ML, Bischoff H, Reck M, Sellers MV, Watkins CL, Speake G, Armour AA, Kim ES. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol. 2010 Feb 10;28(5):744-52. doi: 10.1200/JCO.2009.24.3030. Epub 2009 Dec 28. — View Citation

Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, Chao TY, Nakagawa K, Chu DT, Saijo N, Duffield EL, Rukazenkov Y, Speake G, Jiang H, Armour AA, To KF, Yang JC, Mok TS. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011 Jul 20;29(21):2866-74. doi: 10.1200/JCO.2010.33.4235. Epub 2011 Jun 13. — View Citation

Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, Milanowski J, Karnicka-Mlodkowski H, Pesek M, Serwatowski P, Ramlau R, Janaskova T, Vansteenkiste J, Strausz J, Manikhas GM, Von Pawel J. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007 Apr 20;25(12):1545-52. — View Citation

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Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. — View Citation

Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA; TRIBUTE Investigator Group. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005 Sep 1;23(25):5892-9. Epub 2005 Jul 25. — View Citation

Hirsch FR, Varella-Garcia M, Bunn PA Jr, Franklin WA, Dziadziuszko R, Thatcher N, Chang A, Parikh P, Pereira JR, Ciuleanu T, von Pawel J, Watkins C, Flannery A, Ellison G, Donald E, Knight L, Parums D, Botwood N, Holloway B. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol. 2006 Nov 1;24(31):5034-42. — View Citation

Horgan AM, Bradbury PA, Amir E, Ng R, Douillard JY, Kim ES, Shepherd FA, Leighl NB. An economic analysis of the INTEREST trial, a randomized trial of docetaxel versus gefitinib as second-/third-line therapy in advanced non-small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1805-11. doi: 10.1093/annonc/mdq682. Epub 2011 Jan 27. — View Citation

Keedy VL, Temin S, Somerfield MR, Beasley MB, Johnson DH, McShane LM, Milton DT, Strawn JR, Wakelee HA, Giaccone G. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011 May 20;29(15):2121-7. doi: 10.1200/JCO.2010.31.8923. Epub 2011 Apr 11. — View Citation

Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. doi: 10.1016/S0140-6736(08)61758-4. — View Citation

Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, Ahn MJ, Ahn JS, Suh C, Kim SW. Randomized Phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res. 2010 Feb 15;16(4):1307-14. doi: 10.1158/1078-0432.CCR-09-1903. Epub 2010 Feb 9. — View Citation

Marchetti A, Martella C, Felicioni L, Barassi F, Salvatore S, Chella A, Camplese PP, Iarussi T, Mucilli F, Mezzetti A, Cuccurullo F, Sacco R, Buttitta F. EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol. 2005 Feb 1;23(4):857-65. — View Citation

Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K, Shinkai T, Negoro S, Imamura F, Eguchi K, Takeda K, Inoue A, Tomii K, Harada M, Masuda N, Jiang H, Itoh Y, Ichinose Y, Saijo N, Fukuoka M. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol. 2008 Sep 10;26(26):4244-52. doi: 10.1200/JCO.2007.15.0185. — View Citation

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19. — View Citation

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Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N, Gressot L, Vincent M, Burkes R, Coughlin S, Kim Y, Berille J. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000 May;18(10):2095-103. — View Citation

Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. — View Citation

Taron M, Ichinose Y, Rosell R, Mok T, Massuti B, Zamora L, Mate JL, Manegold C, Ono M, Queralt C, Jahan T, Sanchez JJ, Sanchez-Ronco M, Hsue V, Jablons D, Sanchez JM, Moran T. Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res. 2005 Aug 15;11(16):5878-85. — View Citation

van Zandwijk N, Mathy A, Boerrigter L, Ruijter H, Tielen I, de Jong D, Baas P, Burgers S, Nederlof P. EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer. Ann Oncol. 2007 Jan;18(1):99-103. Epub 2006 Oct 23. — View Citation

* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		12 months after the last patient is randomized	No
Secondary	Progression Free Survival		with 4 years and 12 months after the last patient is randomized	No
Secondary	Response assessed with RECIST criteria		within 4 years	No
Secondary	Quality of Life assessed with QLQ-C30 and QLQ-LC13 questionnaires		within 4 years	No
Secondary	Toxicity, graded according to the NCI-CTAE version 3.0		within 4 years	Yes
Secondary	Frequency and nature of serious adverse reactions		within 4 years	Yes
Secondary	Premature withdrawals		within 4 years	Yes