Clin Oncol | Volume 7, Issue 1 | Research Article | Open Access

Erlotinib Treatment Beyond Progression in EGFR Mutant Patients Who Have Responded to EGFR TKIs in Stage IIIB/IV NSCLC: An Open Label Randomized Trial

Jussi P Koivunen1*, Sanna Iivanainen1, Eeva-Maija Nieminen2, Aija Knuuttila2, Taneli Saariaho3, Eira Ritanen4, Jarkko Ahvonen5 and Jami Mandelin6

1Department of Oncology and Radiotherapy, Oulu University Hospital and MRC Oulu, Finland
2Department of Pulmonary Medicine, Helsinki University Hospital and University of Helsinki, Finland
3Department of Pulmonary Medicine, Turku University Hospital, Finland
4Department of Oncology, Kuopio University Hospital, Finland
5Department of Oncology, Tampere University Hospital, Finland
6University of Helsinki, Finland

*Correspondance to: Jussi P Koivunen 

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Treatment of EGFR mutation-positive advanced Non-Small-Cell Lung Cancer (NSCLC) beyond progression using EGFR TKIs is a valid therapeutic option in oligo- or asymptomatic progression. Previous studies have shown that combination of 1st generation EGFR TKIs to chemotherapy increases Progression-Free (PFS) and Overall Survival (OS) in 1st line treatment of EGFR positive
disease but the beneficial role of this combination is unproven in later treatment lines. In this open-label, phase 2 trial, we randomly assigned 18 patients with previously 1st generation EGFR TKI treated, EGFR mutation-positive advanced NSCLC in a 1:1 ratio to receive either sequential combination of erlotinib + chemotherapy (erlotinib d5-18 on 21d chemotherapy cycle) or standard chemotherapy. The primary endpoint was investigator-assessed Progression-Free Survival (PFS).
The median PFS was similar with erlotinib + chemotherapy and chemotherapy alone (4.2 vs. 3.4 months; CI: 3.5 to 4.8; p=0.305). The clinical benefit rate was comparable in the two groups: 66.7% with erlotinib + chemotherapy and 63.0% with standard chemotherapy (p=NS). The median overall survival was similar with erlotinib + chemotherapy and chemotherapy (9.7 vs. 8.3 months; 95% CI, 6.5 to 10.1; p=0.402). Adverse events of grade ≥ 3 were analogous in both groups (44.4% in both), 
neutropenia/neutropenic fever (33.3%) and infection (22.2%) being the most common.
The sequential combination of erlotinib + chemotherapy is a safe option in the treatment of patients who have progressed on 1st generation TKIs compared to chemotherapy alone. The primary endpoint, PFS, was consistent in both arms though statistically insignificant.


NSCLC; EGFR mutation; Acquired resistance; Chemotherapy; EGFR TKI


Koivunen JP, Iivanainen S, Nieminen E-M, Knuuttila A, Saariaho T, Ritanen E, et al. Erlotinib Treatment Beyond Progression in EGFR Mutant Patients Who Have Responded to EGFR TKIs in Stage IIIB/IV NSCLC: An Open Label Randomized Trial. Clin Oncol. 2022;7:1904..

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