SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC

Abstract

8001 Background: Erlotinib (E), a small-molecule EGFR TKI, is proven to extend survival versus placebo (P) in 2nd/3rd-line advanced NSCLC. The phase III SATURN study (BO18192) was initiated to evaluate E as maintenance therapy after standard 1st-line platinum-based chemotherapy (CT) in advanced NSCLC. Methods: Patients with no evidence of disease progression after 4 cycles of CT were randomized to receive either E 150 mg/day or P until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) in all patients and the co-primary endpoint was PFS in EGFR immunohistochemistry-positive (IHC+) patients. Results: A total of 1,949 patients entered the CT phase, of whom 889 were randomized to E (n=438) or P (n=451). Median age was 60 years for both arms. Baseline characteristics for E and P arms (%): male/female: 73/27 and 75/25; adenocarcinoma + BAC/squamous-cell/other: 47/38/15 and 44/43/13; stage IIIB/IV: 26/74 and 24/76; Caucasian/Asian/other: 84/14/2 and 83/15/2; ECOG PS 0/1: 31/69 and 32/68; current/former/never smoker: 55/28/18 and 56/27/17. PFS (by investigator assessment; confirmed by independent review) was significantly prolonged with E versus P in all patients (HR 0.71 [95% CI 0.62–0.82]; p<.0001) and in EGFR IHC+ patients (HR 0.69 [95% CI 0.58–0.82]; p<.0001). Subgroup analyses will be reported. Response rate was 12% with E versus 5% with P. Disease control rate (complete response + partial response + stable disease >12 wks) was 40.8% with E versus 27.4% with P (p<.0001). OS data are not yet mature. E was well tolerated: the majority of treatment-related adverse events (AEs) were grade 1/2. AEs reported in ≥10% of all patients were rash (60% with E versus 9% with P) and diarrhea (20% with E versus 5% with P); again, most were grade 1/2. Only 2.3% of patients receiving E had a serious treatment-related AE and 2.8% withdrew due to a treatment-related AE. Conclusions: The SATURN study met its primary and co-primary endpoints with high statistical significance. Erlotinib in the 1st-line maintenance setting is well tolerated, and significantly improves disease control and delays progression versus placebo across patient subgroups. [Table: see text]

Futility for subgroup analyses in the adaptive signature design

“…Simulation results under the null hypothesis (Table 4, rows [1][2][3][4][5][6][7][8][9][10][11][12] show that the proposed method controls the type I error. Under the alternative hypothesis, some power is lost with respect to the subgroup design without futility.…”

“…both will be considered as primary analyses (e.g. Sequential Tarceva in Unresectable NSCLC (SATURN) study 2 ). Adaptive designs with subgroup selection have been considered.…”

Hemorrhage of brain metastasis from non-small cell lung cancer post gefitinib therapy: two case reports and review of the literature

“…It is expressed in a variety of human cancers including NSCLC (40%-80%), colorectal (25%-77%), pancreatic (30%-50%), breast (15%-30%), ovarian (35%-70%), prostate (40%) and gastric (33%) cancers [ 1 ]. Among the above-mentioned cancers, NSCLC was one of the most frequently studied objects of EGFR-targeted therapy, as evidenced by such clinical trials as INTEREST, ISEL (for gefitinib), and BR21 and SATURN (for erlotinib, another EGFR-TKI) [ 2 , 4 , 10 , 11 ].…”

Updates in non-small cell lung cancer - insights from the 2009 45th annual meeting of the American Society of Clinical Oncology

“…Sequential erlotinib in unresectable NSCLC (SATURN) trial was a placebo-controlled, randomized, double-blind, phase III study that enrolled 889 patients with advanced NSCLC, and patients were randomized to erlotinib or placebo if their cancer did not progress after at least four cycles of first-line platinum-based chemotherapy [ 17 ]. The study met its primary endpoint demonstrating a significantly improved PFS with erlotinib in all comers (HR 0.71; p < 0.0001), and in EGFR-positive subgroup (HR 0.69; p < 0.0001).…”