title: Predictive and prognostic factors in second- and third-line erlotinib treatment in NSCLC patients with known status of the EGFR gene.
abstract: Erlotinib is a reversible tyrosine kinase inhibitor of epidermal growth factor receptor (TKI EGFR). In Poland, as of July 2012, it is used in the treatment only of patients with non-small cell lung cancer (NSCLC) and with EGFR mutation gene after standard chemotherapy failure. The effectiveness of erlotinib in second- or third-line treatment of NSCLC patients without EGFR activating mutation gene remains debatable. Clinical trial results indicated that TKI EGFR showed an efficacy of 70‑80% in patients with EGFR mutations, while the clinical response to treatment among unselected Caucasian patients is only 10%. The present study was conducted in a group of 71 patients with inoperable, locally advanced or metastatic NSCLC treated with erlotinib as the second- or third-line therapy. Molecular tests (examination of EGFR mutation and gene amplification) were carried out retrospectively. Objective response rate, overall survival (OS) and progression-free survival (PFS) were calculated. Effects of clinical and molecular factors including the presence of EGFR mutations, EGFR gene amplification, patient performance status, rash, smoking status, time from diagnosis to start of therapy, weight loss and the serum LDH levels were analyzed. An objective response in the form of partial response occurred in only 5 patients (7%), who carried EGFR gene mutation. Median time to PFS for the entire group of patients was 1.5 months and median OS was 10 months. The strongest factors increasing the risk of progression in patients treated with erlotinib were the absence of activating mutations in the EGFR gene (6‑fold increased risk) and no treatment‑related rash (4.5‑fold increased risk). The most important factors affecting the risk of early mortality were poor performance status (HR 37.344; P>0.0001), no treatment-related rash (HR 14.9348; P=0.0002) and a short response time on the first-line chemotherapy (HR 9.519; P=0.0445).
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.forename: Dariusz M
authors.initials: DM
authors.lastname: Kowalski
authors.forename: Kamila Wojas
authors.initials: KW
authors.lastname: Krawczyk
authors.forename: Michał
authors.initials: M
authors.lastname: Szczyrek
authors.forename: Radosław
authors.initials: R
authors.lastname: Mlak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rolski
authors.forename: Aneta
authors.initials: A
authors.lastname: Szudy
authors.forename: Robert
authors.initials: R
authors.lastname: Kieszko
authors.forename: Kinga
authors.initials: K
authors.lastname: Winiarczyk
authors.forename: Janusz
authors.initials: J
authors.lastname: Milanowski
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors