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 Torniai; D 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

doi:10.1007/s12094-019-02193-w

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

IRCCS Fondazione Policlinico Universitario A. Gemelli

Research output: Contribution to journal › Article › peer-review

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 language	English
Journal	Clinical and Translational Oncology
DOIs	https://doi.org/10.1007/s12094-019-02193-w
Publication status	E-pub ahead of print - Aug 7 2019

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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

Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients : a multicenter study of clinicians' attitudes. / 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; Torniai, M; Cortinovis, D; Sala, E; Maggioni, C; Follador, A; Macerelli, M; Nigro, O; Tuzi, A; Iacono, D; Migliorino, M R; Banna, G; Porzio, G; Cannita, K; Ferrara, M G; Bria, E; Galetta, D; Ficorella, C; Tiseo, M.

In: Clinical and Translational Oncology, 07.08.2019.

Research output: Contribution to journal › Article › peer-review

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, Torniai, M, Cortinovis, D, Sala, E, Maggioni, C, Follador, A, Macerelli, M, Nigro, O, Tuzi, A, Iacono, D, Migliorino, MR, Banna, G, Porzio, G, Cannita, K, Ferrara, MG, Bria, E, Galetta, D, Ficorella, C & 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

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 ; Torniai, M ; Cortinovis, D ; Sala, E ; Maggioni, C ; Follador, A ; Macerelli, M ; Nigro, O ; Tuzi, A ; Iacono, D ; Migliorino, M R ; Banna, G ; Porzio, G ; Cannita, K ; Ferrara, M G ; Bria, E ; Galetta, D ; Ficorella, C ; Tiseo, M. / Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients : a multicenter study of clinicians' attitudes. In: Clinical and Translational Oncology. 2019.

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

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.",

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

year = "2019",

month = aug,

day = "7",

doi = "10.1007/s12094-019-02193-w",

language = "English",

journal = "Clinical and Translational Oncology",

issn = "1699-048X",

publisher = "Springer-Verlag Italia",

}

TY - JOUR

T1 - Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients

T2 - a multicenter study of clinicians' attitudes

AU - Cortellini, A

AU - Leonetti, A

AU - Catino, A

AU - Pizzutillo, P

AU - Ricciuti, B

AU - De Giglio, A

AU - Chiari, R

AU - Bordi, P

AU - Santini, D

AU - Giusti, R

AU - De Tursi, M

AU - Brocco, D

AU - Zoratto, F

AU - Rastelli, F

AU - Citarella, F

AU - Russano, M

AU - Filetti, M

AU - Marchetti, P

AU - Berardi, R

AU - Torniai, M

AU - Cortinovis, D

AU - Sala, E

AU - Maggioni, C

AU - Follador, A

AU - Macerelli, M

AU - Nigro, O

AU - Tuzi, A

AU - Iacono, D

AU - Migliorino, M R

AU - Banna, G

AU - Porzio, G

AU - Cannita, K

AU - Ferrara, M G

AU - Bria, E

AU - Galetta, D

AU - Ficorella, C

AU - Tiseo, M

PY - 2019/8/7

Y1 - 2019/8/7

N2 - 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.

AB - 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.

U2 - 10.1007/s12094-019-02193-w

DO - 10.1007/s12094-019-02193-w

M3 - Article

C2 - 31392645

JO - Clinical and Translational Oncology

JF - Clinical and Translational Oncology

SN - 1699-048X

ER -