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.

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 & TRANSLATIONAL ONCOLOGY. - ISSN 1699-048X. - 22:6(2020), pp. 844-851. [10.1007/s12094-019-02193-w]

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

Santini D.;Giusti R.;Filetti M.;Marchetti P.;
2020

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.
2020
beyond progression; egfr; nsclc; osimertinib; progression of disease; t790m; acrylamides; adult; aged; aged; 80 and over; aniline compounds; antineoplastic agents; carcinoma; non-small-cell lung; combined modality therapy; disease progression; erbb receptors; female; health knowledge; attitudes; practice; humans; italy; lung neoplasms; male; middle aged; mutation; survival analysis; treatment outcome
01 Pubblicazione su rivista::01a Articolo in rivista
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 & TRANSLATIONAL ONCOLOGY. - ISSN 1699-048X. - 22:6(2020), pp. 844-851. [10.1007/s12094-019-02193-w]
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