Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians’ attitudes

A. Cortellini, A. Leonetti, A. Catino, P. Pizzutillo, B. Ricciuti, A. De Giglio, R. Chiari, P. Bordi, D. Santini, R. Giusti, M. De Tursi, D. Brocco, F. Zoratto, F. Rastelli, F. Citarella, M. Russano, M. Filetti, P. Marchetti, R. Berardi, M. TorniaiD. Cortinovis, E. Sala, C. Maggioni, A. Follador, M. Macerelli, O. Nigro, A. Tuzi, D. Iacono, M. R. Migliorino, G. Banna, G. Porzio, K. Cannita, M. G. Ferrara, E. Bria, D. Galetta, C. Ficorella, M. Tiseo

Research output: Contribution to journalArticle

Abstract

Background: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed “non-drugable” progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. Methods: We conducted a study on “post-progression” (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), “switched therapies” or best supportive care only (BSC). Results: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35–0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33–0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68–1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52–1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). Conclusion: Our study confirmed that in clinical practice, in case of “non-druggable” disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.

Original languageEnglish
JournalClinical and Translational Oncology
DOIs
Publication statusE-pub ahead of print - Jan 1 2019

Keywords

  • Beyond progression
  • EGFR
  • NSCLC
  • Osimertinib
  • Progression of disease
  • T790M

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cortellini, A., Leonetti, A., Catino, A., Pizzutillo, P., Ricciuti, B., De Giglio, A., Chiari, R., Bordi, P., Santini, D., Giusti, R., De Tursi, M., Brocco, D., Zoratto, F., Rastelli, F., Citarella, F., Russano, M., Filetti, M., Marchetti, P., Berardi, R., ... Tiseo, M. (2019). Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians’ attitudes. Clinical and Translational Oncology. https://doi.org/10.1007/s12094-019-02193-w