A Cortellini1,2, A Leonetti3, A Catino4, P Pizzutillo4, B Ricciuti5, A De Giglio5, R Chiari6, P Bordi3, D Santini7, R Giusti8, M De Tursi9, D Brocco10, F Zoratto11, F Rastelli12, F Citarella7, M Russano7, M Filetti8, P Marchetti8,13, R Berardi14, M Torniai14, D Cortinovis15, E Sala15, C Maggioni15, A Follador16, M Macerelli16, O Nigro17, A Tuzi17, D Iacono18, M R Migliorino18, G Banna19, G Porzio20,21, K Cannita21, M G Ferrara22,23, E Bria22,23, D Galetta4, C Ficorella20,21, M Tiseo3,24. 1. Medical Oncology Unit, St. Salvatore Hospital, Via Vetoio, 67100, L'Aquila, Italy. alessiocortellini@gmail.com. 2. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. alessiocortellini@gmail.com. 3. Medical Oncology, University Hospital of Parma, Parma, Italy. 4. Thoracic Oncology Unit, Clinical Cancer Centre "Giovanni Paolo II", Bari, Italy. 5. Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy. 6. Medical Oncology, Ospedali Riuniti Padova Sud "Madre Teresa Di Calcutta", Monselice, Italy. 7. Medical Oncology, Campus Bio-Medico University, Rome, Italy. 8. Medical Oncology, Sant'Andrea Hospital, Rome, Italy. 9. Department of Medical, Oral and Biotechnological Sciences, University G. D'Annunzio, Chieti-Pescara, Italy. 10. Clinical Oncology Unit, S.S. Annunziata Hospital, Chieti, Italy. 11. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy. 12. Medical Oncology, Fermo Area Vasta 4, Fermo, Italy. 13. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy. 14. Oncology Clinic, Università Politecnica Delle Marche, Ospedali Riuniti Di Ancona, Ancona, Italy. 15. Medical Oncology, Ospedale San Gerardo, Monza, Italy. 16. Department of Oncology, University Hospital Santa Maria Della Misericordia, Udine, Italy. 17. Medical Oncology, ASST-Sette Laghi, Varese, Italy. 18. Pulmonary Oncology Unit, St. Camillo-Forlanini Hospital, Rome, Italy. 19. Medical Oncology Unit, Cannizzaro Hospital, Catania, Italy. 20. Medical Oncology Unit, St. Salvatore Hospital, Via Vetoio, 67100, L'Aquila, Italy. 21. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. 22. Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy. 23. Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy. 24. Department of Medicine and Surgery, University of Parma, Parma, Italy.
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.
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.
Entities:
Keywords:
Beyond progression; EGFR; NSCLC; Osimertinib; Progression of disease; T790M
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