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Multicenter Study
. 2020 Jun;22(6):844-851.
doi: 10.1007/s12094-019-02193-w. Epub 2019 Aug 7.

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

A Cortellini  1   2 , A Leonetti  3 , A Catino  4 , P Pizzutillo  4 , B Ricciuti  5 , A De Giglio  5 , R Chiari  6 , P Bordi  3 , D Santini  7 , R Giusti  8 , M De Tursi  9 , D Brocco  10 , F Zoratto  11 , F Rastelli  12 , F Citarella  7 , M Russano  7 , M Filetti  8 , P Marchetti  8   13 , R Berardi  14 , M Torniai  14 , D Cortinovis  15 , E Sala  15 , C Maggioni  15 , A Follador  16 , M Macerelli  16 , O Nigro  17 , A Tuzi  17 , D Iacono  18 , M R Migliorino  18 , G Banna  19 , G Porzio  20   21 , K Cannita  21 , M G Ferrara  22   23 , E Bria  22   23 , D Galetta  4 , C Ficorella  20   21 , M Tiseo  3   24
Affiliations
Multicenter Study

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

A Cortellini et al. Clin Transl Oncol. 2020 Jun.

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.

Keywords: Beyond progression; EGFR; NSCLC; Osimertinib; Progression of disease; T790M.

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