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.
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.
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).
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.
F Hoffmann-La Roche Ltd.
Copyright 2010 Elsevier Ltd. All rights reserved.