Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program.
| Title: | Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program. |
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| Authors: | Passiglia F; Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano (TO), Italy.; Lucia Reale M; Medical Oncology Unit, Vito Fazzi Hospital, Lecce, Italy.; Lo Russo G; Thoracic Unit, Department of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy.; Pasello G; Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy; Medical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.; Minuti G; Clinical Trial Unit: Phase 1 and Precision Medicine, National Cancer Institute, IRCCS, Regina Elena, Rome, Italy.; Bulotta A; Department of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.; Galetta D; Medical Thoracic Oncology Unit, Istituto Tumori Giovanni Paolo II, Bari, Italy.; Pelizzari G; Dipartimento di Oncologia, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.; Sini C; Medical Oncology, Ospedale Giovanni Paolo II - ATS Sardegna - ASSL Olbia, Olbia, Italy.; Bria E; Medical Oncology, Department of Traslational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.; Roca E; Thoracic Oncology, Lung Unit, P. Pederzoli Hospital, Peschiera Del Garda (VR), Italy.; Pilotto S; Department of Engineering for Innovation Medicine University of Verona, Section of Oncology, Verona, Italy.; Genova C; Lung Cancer Unit, Università degli Studi di Genova e Ospedale Policlinico San Martino IRCCS - DiMI, Genova, Italy.; Metro G; Medical Oncology Department, Ospedale S. Maria della Misericordia, Perugia, Italy.; Citarella F; Oncology Department, Policlinico Universitario Campus Bio-Medico, Rome, Italy.; Chiari R; UOC Oncologia, AST Pesaro Urbino, Pesaro, Italy.; Cortinovis D; Fondazione IRCCS San Gerardo dei Tintori Monza, Monza, Italy.; Delmonte A; Department of Medical Oncology, Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori' (IRST) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy.; Russo A; Medical Oncology Unit, Centro Oncologico Ospedale Papardo, Messina, Italy.; Tiseo M; Department of Medicine and Surgery, University of Parma and Medical Oncology Unit, University Hospital of Parma, Parma, Italy.; Cerea G; Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.; Carta A; SC Oncologia Medica, Ospedale Businco - ARNAS G. Brotzu, Cagliari, Italy.; Scotti V; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.; Vavalà T; Azienda Ospedaliero Universitaria (AOU) Città della Salute e della Scienza, Department of Oncology, SC Oncologia 1, Torino, Italy.; Brambilla M; Thoracic Unit, Department of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy.; Buffoni L; Medical Oncology Department, Humanitas Gradenigo, Turin, Italy.; Buosi R; Department of Medical Oncology, Ospedale Santo Spirito, Casale Monferrato, Alessandria, Italy.; Catania C; Medical Oncology Department, Humanitas Gavazzeni, Bergamo, Italy.; Gori S; Department of Medical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy.; Grisanti S; Medical Oncology Department, Azienda Ospedaliera Spedali Civili, Brescia, Italy.; Agustoni F; Department of Internal Medicine and Medical Therapy, University of Pavia, and Department of Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Garbo E; Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano (TO), Italy.; Malapelle U; Department of Public Health, University Federico II of Naples, Naples, Italy.; Novello S; Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano (TO), Italy. Electronic address: silvia.novello@unito.it. |
| Source: | Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2024 Jan; Vol. 187, pp. 107444. Date of Electronic Publication: 2023 Dec 15. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Scientific Publishers Country of Publication: Ireland NLM ID: 8800805 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8332 (Electronic) Linking ISSN: 01695002 NLM ISO Abbreviation: Lung Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier Scientific Publishers; Original Publication: Amsterdam, The Netherlands : Elsevier, c1985- |
| MeSH Terms: | Carcinoma, Non-Small-Cell Lung*/drug therapy ; Carcinoma, Non-Small-Cell Lung*/genetics ; Lung Neoplasms*/drug therapy ; Lung Neoplasms*/genetics; Italy/epidemiology ; Proto-Oncogene Proteins p21(ras)/genetics ; Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Female ; Quality of Life ; Mutation ; Piperazines ; Pyridines ; Pyrimidines |
| Abstract: | Background: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP).; Methods: Sotorasib (960 mg, orally, once daily) was available on physician request for KRASp.G12C mutant advanced NSCLC patients. Clinical-pathological and molecular data were collected from the Italian ATLAS real-world registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed.; Results: A total of 196 advanced NSCLC patients were treated across 30 Italian centers. Median age was 69 years old (range 33-86). Most patients were male (61 %), former (49 %) or current smokers (43 %), with ECOG-PS 0/1 (84 %) and adenocarcinoma subtype (90 %). 45 % and 32 % of patients received sotorasib in 2nd and 3rd line, respectively. Overall, response rate was 26 % and the median duration of response was 5.7 months (95 % CI: 4.4-7.0). Median PFS and OS were 5.8 months (95 % CI: 5 - 6.5) and 8.2 months (95 % CI: 6.3 - 9.9). Grade 3-4 TRAEs occurred in 16.5 % of patients, with Grade ≥ 3 liver enzyme increase and TRAEs-related discontinuation reported in 12 % and 4.6 % of cases.; Conclusion: Real-world data from the Italian EAP confirm the tolerability and effectiveness of sotorasib in patients with KRASp.G12C-mutated advanced NSCLC and highlight the value of the national ATLAS network as source of real-world evidence driving the clinical management of NSCLC patients.; (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: KRASp.G12C; Non-small cell lung cancer; Sotorasib; Targeted therapy |
| Substance Nomenclature: | EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)); 2B2VM6UC8G (sotorasib); 0 (Piperazines); 0 (Pyridines); 0 (Pyrimidines) |
| Entry Date(s): | Date Created: 20231229 Date Completed: 20240108 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.lungcan.2023.107444 |
| PMID: | 38157806 |
| Database: | MEDLINE |
Journal Article