Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L)

Introduction: Alternation of osimertinib and afatinib is a potential approach to overcome osimertinib resistance and to allow complementation of drug efficacy without compromising safety in patients with epidermal growth factor receptor gene (EGFR)–mutated non–small cell lung cancer (NSCLC). Methods...

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Main Authors: Azuma, K. (Author), Chiba, Y. (Author), Daga, H. (Author), Fujimoto, D. (Author), Hataji, O. (Author), Hayashi, H. (Author), Hirano, K. (Author), Ikeda, S. (Author), Nakagawa, K. (Author), Nakamura, A. (Author), Nishio, K. (Author), Okada, H. (Author), Sakai, K. (Author), Sakata, S. (Author), Tachihara, M. (Author), Yamamoto, N. (Author), Yano, Y. (Author), Yokoyama, T. (Author), Yonesaka, K. (Author)
Format: Article
Language:English
Published: Elsevier Ireland Ltd 2022
Subjects:
Online Access:View Fulltext in Publisher
LEADER 03110nam a2200397Ia 4500
001 10.1016-j.lungcan.2022.04.004
008 220706s2022 CNT 000 0 und d
020 |a 01695002 (ISSN) 
245 1 0 |a Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L) 
260 0 |b Elsevier Ireland Ltd  |c 2022 
856 |z View Fulltext in Publisher  |u https://doi.org/10.1016/j.lungcan.2022.04.004 
520 3 |a Introduction: Alternation of osimertinib and afatinib is a potential approach to overcome osimertinib resistance and to allow complementation of drug efficacy without compromising safety in patients with epidermal growth factor receptor gene (EGFR)–mutated non–small cell lung cancer (NSCLC). Methods: Treatment-naive patients with stage IV NSCLC harboring an activating EGFR mutation (L858R or exon-19 deletion) were enrolled. Alternating cycles of osimertinib at 80 mg/day for 8 weeks followed by afatinib at 20 mg/day for 8 weeks were administered. The primary end point was 12-month progression-free survival (PFS) probability. Results: Forty-six patients were enrolled and treated with study therapy. The 12-month PFS probability was 70.2% (60% confidence interval [CI], 63.9–75.6%; 95% CI, 54.2–81.5%), which did not meet the primary end point. After a median follow-up time of 25.7 months, the median PFS was 21.3 months (95% CI, 16.3 months–not reached). The overall response rate was 69.6% (95% CI, 54.2–82.3%). The most common treatment-related adverse events (any grade or grade ≥ 3, respectively) were diarrhea (73.9%, 4.3%), rash acneiform (63.0%, 2.2%), and paronychia (52.2%, 0%). Five cases of pneumonitis, two of grade 2 and thres of grade 3, were apparent, all of which developed during osimertinib treatment. Exploratory evaluation of circulating tumor DNA suggested that coexisting TP53 mutations did not influence PFS for the alternating therapy. Conclusions: Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy. © 2022 The Authors 
650 0 4 |a Afatinib 
650 0 4 |a Epidermal growth factor receptor (EGFR) 
650 0 4 |a Non-small cell lung cancer (NSCLC) 
650 0 4 |a Osimertinib 
700 1 0 |a Azuma, K.  |e author 
700 1 0 |a Chiba, Y.  |e author 
700 1 0 |a Daga, H.  |e author 
700 1 0 |a Fujimoto, D.  |e author 
700 1 0 |a Hataji, O.  |e author 
700 1 0 |a Hayashi, H.  |e author 
700 1 0 |a Hirano, K.  |e author 
700 1 0 |a Ikeda, S.  |e author 
700 1 0 |a Nakagawa, K.  |e author 
700 1 0 |a Nakamura, A.  |e author 
700 1 0 |a Nishio, K.  |e author 
700 1 0 |a Okada, H.  |e author 
700 1 0 |a Sakai, K.  |e author 
700 1 0 |a Sakata, S.  |e author 
700 1 0 |a Tachihara, M.  |e author 
700 1 0 |a Yamamoto, N.  |e author 
700 1 0 |a Yano, Y.  |e author 
700 1 0 |a Yokoyama, T.  |e author 
700 1 0 |a Yonesaka, K.  |e author 
773 |t Lung Cancer