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Cited by 374Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study

Ciuleanu, Tudor, Stelmakh, Lilia, Cicenas, Saulius, Miliauskas, Skaidrius, Grigorescu, Alexandru Calin, Hillenbach, Carina, Johannsdottir, Hrefna Kristin, Klughammer, Barbara +1 more·2012·The Lancet Oncology
DOI 10.1016/s1470-2045(11)70385-0
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Abstract

Background Erlotinib, docetaxel, and pemetrexed are approved for the second-line treatment of non-small-cell lung cancer (NSCLC), but no head-to-head data from large clinical trials are available. We undertook the Tarceva In Treatment of Advanced NSCLC (TITAN) study to assess the efficacy and tolerability of second-line erlotinib versus chemotherapy in patients with refractory NSCLC.Methods TITAN was an international, randomised multicentre, open-label, phase 3 study that was done at 77 sites in 24 countries. Chemotherapy-naive patients with locally advanced, recurrent, or metastatic NSCLC received up to four cycles of first-line platinum doublet chemotherapy, after which patients with disease progression during or immediately after chemotherapy were offered enrolment into TITAN. Enrolled patients were randomly assigned (1:1) by a minimisation method to ensure balanced stratification, to receive erlotinib 150 mg/day or chemotherapy (standard docetaxel or pemetrexed regimens, at the treating investigators' discretion), until unacceptable toxicity, disease progression, or death. Patients were stratified by disease stage, Eastern Cooperative Oncology Group performance status, smoking history, and region of residence. The primary endpoint was overall survival in the intention-to-treat population. TITAN was halted prematurely because of slow recruitment. This study is registered with ClinicalTrials.gov, number NCT00556322.Findings Between April 10, 2006, and Feb 24, 2010, 2590 chemotherapy-naive patients were treated with first-line platinum doublet chemotherapy, of whom 424 had disease progression and were enrolled into TITAN. 203 patients were randomly assigned to receive erlotinib and 221 were assigned to receive chemotherapy. Median follow-up was 27·9 months (IQR 11·0-36·0) in the erlotinib group and 24·8 months (12·1-41·6) in the chemotherapy group. Median overall survival was 5·3 months (95% CI 4·0-6·0) with erlotinib and 5·5 months (4·4-7·1) with chemotherapy (hazard ratio [HR] 0·96, 95% CI 0·78-1·19; log-rank p=0·73). The adverse-event profile of each group was in line with previous studies. Rash (98/196 [50%] in the erlotinib group vs 10/213 [5%] in the chemotherapy group for all grades; nine [5%] vs none for grade 3 or 4) and diarrhoea (36 [18%] vs four [2%] for all grades; five [3%] vs none for grade 3 or 4) were the most common treatment-related adverse events with erlotinib, whereas alopecia (none vs 23 [11%] for all grades; none vs one [<1%] for grade 3/4) was the most common treatment-related adverse event with chemotherapy.Interpretation No significant differences in efficacy were noted between patients treated with erlotinib and those treated with docetaxel or pemetrexed. Since the toxicity profiles of erlotinib and chemotherapy differ, second-line treatment decisions should take into account patient preference and specific toxicity risk profiles.Funding F Hoffmann-La Roche.

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Authors
Ciuleanu, T., Stelmakh, L., Cicenas, S., Miliauskas, S., Grigorescu, A. C., Hillenbach, C., Johannsdottir, H. K., Klughammer, B., & Gonzalez, E. E.
Affiliations
  • Institute of Oncology Prof. Dr. Ion Chiricuta (RO)
  • First Pavlov State Medical University of St. Petersburg (RU)
  • Lithuanian University of Health Sciences (LT)
  • F. Hoffmann-La Roche AG (CH)
Corresponding author
Ciuleanu, Tudor
ORCID
Venue
The Lancet Oncology
Publisher
Elsevier BV
Published
2012-03
Volume
13
Issue
3
Pages
300-308
ISSN
1470-2045 (ISSN-L)
DOI
10.1016/s1470-2045(11)70385-0
OpenAlex
W2037791152
Cited by
374
References
19
Citations by year
2026: 2 · 2025: 10 · 2024: 1 · 2023: 13 · 2022: 10 · 2021: 21 · 2020: 11 · 2019: 18 · 2018: 19 · 2017: 36 · 2016: 41 · 2015: 59 · 2014: 51 · 2013: 57 · 2012: 25
FWCI
49.54
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Lancet Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • Lithuanian University of Health Sciences (submittedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
erlotinib, non-small cell lung cancer, second-line therapy, docetaxel, pemetrexed, platinum-based chemotherapy, overall survival, EGFR tyrosine kinase inhibitors, disease progression, treatment safety, TITAN trial, head-to-head comparison, poor prognosis patients, metastatic lung cancer, recurrent lung cancer, smoking history, performance status
MeSH terms
Pemetrexed, Erlotinib Hydrochloride, Docetaxel, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Europe, Female, Glutamates, Guanine, Humans, Immunohistochemistry, Lung Neoplasms, Male, Middle Aged, Prospective Studies, Quinazolines, Time Factors, Chi-Square Distribution, Salvage Therapy, Treatment Outcome, Taxoids, Protein Kinase Inhibitors, Kaplan-Meier Estimate, Early Termination of Clinical Trials, ErbB Receptors

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