title: Phase II study of erlotinib for previously treated patients with EGFR wild-type non-small-cell lung cancer, following EGFR mutation status reevaluation with the Scorpion Amplified Refractory Mutation System.
abstract: While assessing the efficacy of erlotinib in patients with epidermal growth factor receptor (EGFR) wild-type (WT) non-small-cell lung cancer (NSCLC), the sensitivity of the method used for the EGFR mutation analysis may affect the evaluation of the efficacy. We conducted a phase II study of erlotinib for previously treated patients with EGFR WT NSCLC screened by the peptide nucleic acid-locked nucleic acid (PNA-LNA) polymerase chain reaction (PCR) clamp method, which is known to be highly sensitive. The primary endpoint was the objective response rate (ORR). Preplanned reevaluation of the EGFR genotype as an exploratory endpoint was performed using the Scorpion Amplification Refractory Mutation System (S-ARMS) assay. Erlotinib was administered daily until disease progression or development of unacceptable toxicity. A total of 53 evaluable patients were enrolled. The histological subtypes were adenocarcinoma in 40 patients, squamous cell carcinoma in 9 patients and not otherwise specified NSCLC in 4 patients. Partial response (PR) was achieved in 6 patients (4 with adenocarcinoma and 2 with squamous cell carcinoma). The ORR was 11.3% [95% confidence interval (CI): 4.3-23.0]. The median progression-free survival (PFS) was 1.8 months (95% CI: 1.2-2.3). Samples from 26 of the 53 patients (49.0%) were available for EGFR mutation reanalysis with the S-ARMS assay. Of these 26 samples, only 1 sample of adenocarcinoma was found to be EGFR mutation-positive (exon 19 deletion) and the patient achieved a PR. The EGFR WT genotype was reconfirmed by the S-ARMS assay in the remaining 25 patients and 2 of these patients exhibited a PR. This study did not meet the primary endpoint, although erlotinib was found to be moderately effective in pretreated patients with EGFR WT NSCLC, even when the EGFR mutational status was confirmed by the highly sensitive PNA-LNA clamp PCR method.
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Morise
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi 489-8642, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Aichi 460-0001, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saka
authors.affiliation: Department of Respiratory Medicine, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Shindoh
authors.affiliation: Department of Respiratory Medicine, Toyohashi Municipal Hospital, Toyohashi, Aichi 441-8085, Japan.
authors.forename: Ryujiro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Respiratory Medicine, Komaki Municipal Hospital, Komaki, Aichi 485-8520, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kojima
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Hase
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi 466-8550, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of Respiratory Medicine, Aichi Cancer Center Aichi Hospital, Okazaki, Aichi 444-0011, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
keywords: epidermal growth factor receptor wild-type; erlotinib; non-small-cell lung cancer