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

Acrylamides / therapeutic use Adult Aged Aged, 80 and over Aniline Compounds / therapeutic use Antineoplastic Agents / therapeutic use Carcinoma, Non-Small-Cell Lung / drug therapy Combined Modality Therapy Disease Progression ErbB Receptors / antagonists & inhibitors Female Health Knowledge, Attitudes, Practice Humans Italy Lung Neoplasms / drug therapy Male Middle Aged Mutation Survival Analysis Treatment Outcome
Beyond progression EGFR NSCLC Osimertinib Progression of disease T790M

Journal

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
ISSN: 1699-3055
Titre abrégé: Clin Transl Oncol
Pays: Italy
ID NLM: 101247119

Informations de publication

Date de publication:
Jun 2020
Historique:
received: 11 07 2019
accepted: 25 07 2019
pubmed: 9 8 2019
medline: 12 1 2021
entrez: 9 8 2019
Statut: ppublish

Résumé

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. 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). 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). 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

DOI: 10.1007/s12094-019-02193-w PMID: 31392645
pubmed: 31392645
doi: 10.1007/s12094-019-02193-w
pii: 10.1007/s12094-019-02193-w
doi:

Substances chimiques

Acrylamides 0
Aniline Compounds 0
Antineoplastic Agents 0
osimertinib 3C06JJ0Z2O
ErbB Receptors EC 2.7.10.1

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

844-851

Références

Novello S, Barlesi F, Califano R, et al. Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v1–v27.
doi: 10.1093/annonc/mdw326
Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454–66. https://doi.org/10.1016/S1470-2045(17)30608-3 (Epub 2017 Sep 25).
doi: 10.1016/S1470-2045(17)30608-3 pubmed: 28958502
Mok TS, Cheng Y, Zhou X, et al. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018;36(22):2244–50. https://doi.org/10.1200/JCO.2018.78.7994 (Epub 2018 Jun 4).
doi: 10.1200/JCO.2018.78.7994 pubmed: 29864379
Yu HA, Riely GJ, Lovly CM. Therapeutic strategies utilized in the setting of acquired resistance to EGFR tyrosine kinase inhibitors. Clin Cancer Res. 2014;20:5898–907. https://doi.org/10.1158/1078-0432.CCR-13-2437 .
doi: 10.1158/1078-0432.CCR-13-2437 pubmed: 25303979 pmcid: 4253858
Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011;3:75ra26. https://doi.org/10.1126/scitranslmed.3002003 .
doi: 10.1126/scitranslmed.3002003 pubmed: 21430269 pmcid: 3132801
Huang WL, Chen YL, Yang SC, et al. Liquid biopsy genotyping in lung cancer: ready for clinical utility? Oncotarget. 2017;8(11):18590–608. https://doi.org/10.18632/oncotarget.14613 .
doi: 10.18632/oncotarget.14613 pubmed: 28099915 pmcid: 5392351
Ma G, Zhang J, Jiang H, et al. Epidermal growth factor receptor T790M mutation as a prognostic factor in EGFR-mutant non-small cell lung cancer patients that acquired resistance to EGFR tyrosine kinase inhibitors. Oncotarget. 2017;8(59):99429–37. https://doi.org/10.18632/oncotarget.19681 .
doi: 10.18632/oncotarget.19681 pubmed: 29245913 pmcid: 5725104
Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629–40. https://doi.org/10.1056/NEJMoa1612674 (Epub 2016 Dec 6).
doi: 10.1056/NEJMoa1612674 pubmed: 27959700
Park K, Jänne PA, Yu C-J, et al. A global phase II study of olmutinib (HM61713) in patients with T790M-positive NSCLC after failure of first-line EGFR-TKI. Ann Oncol. 2017. https://doi.org/10.1093/annonc/mdx671.001 .
doi: 10.1093/annonc/mdx671.001 pubmed: 29117336 pmcid: 5834148
Kelly RJ, Shepherd FA, Krivoshik A, et al. A phase 3, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small cell lung cancer. Ann Oncol. 2019. https://doi.org/10.1093/annonc/mdz128 .
doi: 10.1093/annonc/mdz128 pubmed: 31430371 pmcid: 6938599
Anon (2019) FDA Briefing Document Oncologic Drugs Advisory Committee Meeting April 12, 2016. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM494782.pdf . Accessed 13 June 2019
Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113–25.
doi: 10.1056/NEJMoa1713137
Cortellini A, Buttitta F, Marchetti A, et al. Practical advices about how to handle disease progression during osimertinib in EGFR-mutant NSCLC patients: is it the same old story? J Mol Genet Med. 2018;12:338. https://doi.org/10.4172/1747-0862.1000338 .
doi: 10.4172/1747-0862.1000338
Ramalingam SS, Cheng Y, Zhou C, et al. Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study. Ann Oncol. 2018. https://doi.org/10.1093/annonc/mdy424.063 .
doi: 10.1093/annonc/mdy424.063 pubmed: 29905778 pmcid: 6128180
Gridelli C, Balducci L, Ciardiello F, et al. Treatment of elderly patients with non-small-cell lung cancer: results of an international expert panel meeting of the Italian Association of Thoracic Oncology. Clin Lung Cancer. 2015;16(5):325–33.
doi: 10.1016/j.cllc.2015.02.006
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.
doi: 10.1016/j.ejca.2008.10.026
Kaplan EL, Meier P. Nonparametric estimation of incomplete observations. J Am Stat Assoc. 1958;53:457–81.
doi: 10.1080/01621459.1958.10501452
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1997;17:343–6.
doi: 10.1016/0197-2456(96)00075-X
Cox DR. Regression models and life tables (with discussion). J R Stat Soc (Ser B). 1972;74:187–200.
Ahn MJ, Tsai CM, Shepherd FA, et al. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019;125(6):892–901. https://doi.org/10.1002/cncr.31891 (Epub 2018 Dec 4).
doi: 10.1002/cncr.31891 pubmed: 30512189
Mu Y, Hao X, Yang K, et al. Clinical modality of resistance and subsequent management of patients with advanced non-small cell lung cancer failing treatment with osimertinib. Target Oncol. 2019. https://doi.org/10.1007/s11523-019-00644-6 .
doi: 10.1007/s11523-019-00644-6 pubmed: 31124059 pmcid: 6602986
Le X, Puri S, Negrao MV, et al. Landscape of EGFR-dependent and -independent resistance mechanisms to osimertinib and continuation therapy beyond progression in EGFR-mutant NSCLC. Clin Cancer Res. 2018;24(24):6195–203. https://doi.org/10.1158/1078-0432.CCR-18-1542 .
doi: 10.1158/1078-0432.CCR-18-1542 pubmed: 30228210 pmcid: 6295279
Schmid S, Klingbiel D, Aeppli S, et al. Patterns of progression on osimertinib in EGFR T790M positive NSCLC: a Swiss cohort study. Lung Cancer. 2019;130:149–55. https://doi.org/10.1016/j.lungcan.2019.02.020 .
doi: 10.1016/j.lungcan.2019.02.020 pubmed: 30885336
Vavalà T, Follador A, Tiseo M, et al. BE-POSITIVE: beyond progression after tyrosine kinase inhibitor in EGFR-positive non small cell lung cancer patients: results from a multicenter Italian observational study. Lung Cancer. 2016;95:73–81. https://doi.org/10.1016/j.lungcan.2016.02.011 .
doi: 10.1016/j.lungcan.2016.02.011 pubmed: 27040855
Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol. 2011;8(6):378–82. https://doi.org/10.1038/nrclinonc.2011.44 (Epub 2011 Mar 22).
doi: 10.1038/nrclinonc.2011.44 pubmed: 21423255
Rusthoven CG, Yeh N, Gaspar LE. Radiation therapy for oligometastatic non-small cell lung cancer: theory and practice. Cancer J. 2015;21(5):404–12. https://doi.org/10.1097/PPO.0000000000000143 .
doi: 10.1097/PPO.0000000000000143 pubmed: 26389766
Campo M, Al-Halabi H, Khandekar M, et al. Integration of stereotactic body radiation therapy with tyrosine kinase inhibitors in stage IV oncogene-driven lung cancer. Oncologist. 2016;21(8):964–73. https://doi.org/10.1634/theoncologist.2015-0508 (Epub 2016 Jun 27).
doi: 10.1634/theoncologist.2015-0508 pubmed: 27354669 pmcid: 4978553
Yoshida H, Ooi M, Kim YH. Successful treatment with osimertinib and chemotherapy in a non-small cell lung cancer patient with EGFR mutation and meningeal carcinomatosis. J Thorac Oncol. 2018;13(11):e219–e220220. https://doi.org/10.1016/j.jtho.2018.05.023 .
doi: 10.1016/j.jtho.2018.05.023 pubmed: 30368410
Ichihara E, Hotta K, Ninomiya K, et al. Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer. Lung Cancer. 2019;132:54–8. https://doi.org/10.1016/j.lungcan.2019.02.021 .
doi: 10.1016/j.lungcan.2019.02.021 pubmed: 31097094
Reck M, Mok TSK, Nishio M, et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019;7(5):387–401. https://doi.org/10.1016/S2213-2600(19)30084-0 .
doi: 10.1016/S2213-2600(19)30084-0 pubmed: 30922878 pmcid: 30922878

Auteurs

A Cortellini (A)

Medical Oncology Unit, St. Salvatore Hospital, Via Vetoio, 67100, L'Aquila, Italy. alessiocortellini@gmail.com.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. alessiocortellini@gmail.com.
ORCID: 0000-0002-1209-5735

A Leonetti (A)

Medical Oncology, University Hospital of Parma, Parma, Italy.

A Catino (A)

Thoracic Oncology Unit, Clinical Cancer Centre "Giovanni Paolo II", Bari, Italy.

P Pizzutillo (P)

Thoracic Oncology Unit, Clinical Cancer Centre "Giovanni Paolo II", Bari, Italy.

B Ricciuti (B)

Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.

A De Giglio (A)

Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.

R Chiari (R)

Medical Oncology, Ospedali Riuniti Padova Sud "Madre Teresa Di Calcutta", Monselice, Italy.

P Bordi (P)

Medical Oncology, University Hospital of Parma, Parma, Italy.

D Santini (D)

Medical Oncology, Campus Bio-Medico University, Rome, Italy.

R Giusti (R)

Medical Oncology, Sant'Andrea Hospital, Rome, Italy.

M De Tursi (M)

Department of Medical, Oral and Biotechnological Sciences, University G. D'Annunzio, Chieti-Pescara, Italy.

D Brocco (D)

Clinical Oncology Unit, S.S. Annunziata Hospital, Chieti, Italy.

F Zoratto (F)

Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy.

F Rastelli (F)

Medical Oncology, Fermo Area Vasta 4, Fermo, Italy.

F Citarella (F)

Medical Oncology, Campus Bio-Medico University, Rome, Italy.

M Russano (M)

Medical Oncology, Campus Bio-Medico University, Rome, Italy.

M Filetti (M)

Medical Oncology, Sant'Andrea Hospital, Rome, Italy.

P Marchetti (P)

Medical Oncology, Sant'Andrea Hospital, Rome, Italy.
Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.

R Berardi (R)

Oncology Clinic, Università Politecnica Delle Marche, Ospedali Riuniti Di Ancona, Ancona, Italy.

M Torniai (M)

Oncology Clinic, Università Politecnica Delle Marche, Ospedali Riuniti Di Ancona, Ancona, Italy.

D Cortinovis (D)

Medical Oncology, Ospedale San Gerardo, Monza, Italy.

E Sala (E)

Medical Oncology, Ospedale San Gerardo, Monza, Italy.

C Maggioni (C)

Medical Oncology, Ospedale San Gerardo, Monza, Italy.

A Follador (A)

Department of Oncology, University Hospital Santa Maria Della Misericordia, Udine, Italy.

M Macerelli (M)

Department of Oncology, University Hospital Santa Maria Della Misericordia, Udine, Italy.

O Nigro (O)

Medical Oncology, ASST-Sette Laghi, Varese, Italy.

A Tuzi (A)

Medical Oncology, ASST-Sette Laghi, Varese, Italy.

D Iacono (D)

Pulmonary Oncology Unit, St. Camillo-Forlanini Hospital, Rome, Italy.

M R Migliorino (MR)

Pulmonary Oncology Unit, St. Camillo-Forlanini Hospital, Rome, Italy.

G Banna (G)

Medical Oncology Unit, Cannizzaro Hospital, Catania, Italy.

G Porzio (G)

Medical Oncology Unit, St. Salvatore Hospital, Via Vetoio, 67100, L'Aquila, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

K Cannita (K)

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

M G Ferrara (MG)

Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.

E Bria (E)

Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.

D Galetta (D)

Thoracic Oncology Unit, Clinical Cancer Centre "Giovanni Paolo II", Bari, Italy.

C Ficorella (C)

Medical Oncology Unit, St. Salvatore Hospital, Via Vetoio, 67100, L'Aquila, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

M Tiseo (M)

Medical Oncology, University Hospital of Parma, Parma, Italy.
Department of Medicine and Surgery, University of Parma, Parma, Italy.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides acycliques › Acrylates › Acrylamides › Osimertinib beyond disease progression in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Osimertinib beyond disease progression in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Osimertinib beyond disease progression in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Osimertinib beyond disease progression in...
questionsmedicales.fr › Composés chimiques organiques › Amines › Dérivés de l'aniline › Osimertinib beyond disease progression in...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Osimertinib beyond disease progression in...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire non à petites cellules › Osimertinib beyond disease progression in...
questionsmedicales.fr › Thérapeutique › Association thérapeutique › Osimertinib beyond disease progression in...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Osimertinib beyond disease progression in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs ErbB › Osimertinib beyond disease progression in...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Prestations des soins de santé › Attitude envers la santé › Connaissances, attitudes et pratiques en santé › Osimertinib beyond disease progression in...
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questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Osimertinib beyond disease progression in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Osimertinib beyond disease progression in...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Osimertinib beyond disease progression in...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Osimertinib beyond disease progression in...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Osimertinib beyond disease progression in...