Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study
Open accessAbstract
Background First-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) is usually limited to four to six cycles. Maintenance therapy can delay progression and prolong survival. The oral epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC. We designed the phase 3, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy.Methods Between December, 2005, and May, 2008, 1949 patients were included in the run-in phase (four cycles of platinum-based chemotherapy). At the end of the run-in phase, 889 patients who did not have progressive disease were entered into the main study, and were randomly allocated using a 1:1 adaptive randomisation method through a third-party interactive voice response system to receive erlotinib (150 mg/day; n=438) or placebo (n=451) until progression or unacceptable toxicity. Patients were stratified by EGFR immunohistochemistry status, stage, Eastern Cooperative Oncology Group performance status, chemotherapy regimen, smoking history, and region. Co-primary endpoints were progression-free survival (PFS) in all analysable patients irrespective of EGFR status, and PFS in patients whose tumours had EGFR protein overexpression, as determined by immunohistochemistry. This study is registered with www.ClinicalTrials.gov, number NCT00556712.Findings 884 patients were analysable for PFS; 437 in the erlotinib group and 447 in the placebo group. After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group, median PFS was significantly longer with erlotinib than with placebo: 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group (HR 0.71, 95% CI 0.62-0.82; p<0.0001). PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib (n=307) compared with EGFR-positive patients given placebo (n=311; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group; HR 0.69, 0.58-0.82; p<0.0001). The most common grade 3 or higher adverse events were rash (37 [9%] of 443 patients in the erlotinib group vs none of 445 in the placebo group) and diarrhoea (seven [2%] of 443 patients vs none of 445). Serious adverse events were reported in 47 patients (11%) on erlotinib compared with 34 patients (8%) on placebo. The most common serious adverse event was pneumonia (seven cases [2%] with erlotinib and four [<1%] with placebo).Interpretation Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo. First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy.Funding F Hoffmann-La Roche Ltd.
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In a small subgroup of EGFR mutation-positive patients in the SATURN trial, completing four to six cycles of chemotherapy followed by maintenance TKI was validated.
“it is also reasonable to consider completing four to six cycles followed by a maintenance TKI, an approach validated in a small subgroup of EGFR mutation-positive patients in the SATURN trial.59”
In the erlotinib switch maintenance trial, subgroup analyses showed benefit only in patients with stable disease after induction, not in those with tumour response.
“In the erlotinib trial, subgroup analyses revealed a benefit restricted to patients with stable disease (SD) after induction treatment, as opposed to patients with tumour response.”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [77]
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- Authors
- Cappuzzo, F., Ciuleanu, T., Stelmakh, L., Cicenas, S., Szczésna, A., Juhász, E., Esteban, E., Molinier, O., Brugger, W., Melezínek, I., Klingelschmitt, G., Klughammer, B., & Giaccone, G.
- Affiliations
- Ospedale di Livorno (IT)
- Institute of Oncology Prof. Dr. Ion Chiricuta (RO)
- First Pavlov State Medical University of St. Petersburg (RU)
- Országos Korányi Tbc és Pulmonológiai Intézet (HU)
- Hospital Universitario Central de Asturias (ES)
- Centre Hospitalier du Mans (FR)
- University of Freiburg (DE)
- Roche (United Kingdom) (GB)
- F. Hoffmann-La Roche AG (CH)
- National Institutes of Health (US)
- Corresponding author
- Cappuzzo, Federico
- ORCID
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 11
- Issue
- 6
- Pages
- 521-529
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2100912832
- Cited by
- 1,186
- References
- 26
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 20 · 2022: 14 · 2021: 17 · 2020: 32 · 2019: 34 · 2018: 49 · 2017: 81 · 2016: 73 · 2015: 145 · 2014: 142 · 2013: 172 · 2012: 176
- FWCI
- 146.16
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- 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, maintenance therapy, advanced non-small cell lung cancer, EGFR tyrosine kinase inhibitors, EGFR overexpression, progression-free survival, platinum-based chemotherapy, EGFR immunohistochemistry, second-line therapy, oral anticancer drugs, quality of life, patient-reported outcomes, patient-reported quality of life
- MeSH terms
- Erlotinib Hydrochloride, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunohistochemistry, Lung Neoplasms, Male, Middle Aged, Mutation, Quinazolines, Survival Rate, Disease-Free Survival, Protein Kinase Inhibitors, ErbB Receptors
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