Real-world description of patients with resected epidermal growth factor receptor mutation positive non-small cell lung carcinoma treated with adjuvant osimertinib in an early access program in Italy: the ELBA observational study

Giulia Pasello^1,2*Claudia Proto³Carlo Genova⁴Alberto Pavan⁵Elisa Roca⁶Gabriele Minuti⁷Carmine D'Aniello⁸Raffaele Giusti⁹Sabrina Mariotti¹⁰Francesco Jacopo Romano¹¹Valentina Polo¹²Lorenzo Belluomini¹³Editta Baldini¹⁴Francesca Mazzoni¹⁵Anna Cecilia Bettini¹⁶Valerio Gristina¹⁷Alessandro Russo^18,19Francesco Grossi^20,21Francesca Rita Ogliari^22,23Francesco Gelsomino²⁴Rita Chiari²⁵Emilio Bria²⁶Iacopo Fioroni²⁷Diego Cortinovis^28,29Elio Gregory Pizzutilo³⁰Anna Zanetti³¹Giuseppe Pasqualetti³¹Barbara Roncari³²Lucia Simoni³²Annamaria Catino³³

• ¹Department of Surgery Oncology and Gastroenterology, University of Padova, Padua, Italy
• ²Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy
• ³Istituto Nazionale Tumori, Milan, Italy
• ⁴Ospedale Policlinico San Martino, Genoa, Italy
• ⁵Department of Medical Oncology, AULSS 3 Serenissima, Ospedale dell'Angelo, Venezia, Italy
• ⁶Thoracic Oncology - Lung Unit, Pederzoli Hospital, Peschiera del Garda (VR), Italy
• ⁷Clinical Trials Unit - Phase 1 and Precision Medicine, IRCCS National Cancer Institute Regina Elena, Rome, Italy
• ⁸Unit of Oncology, A.O. dei Colli P.O. Monaldi, Naples, Italy
• ⁹A.O.U. Sant'Andrea, Rome, Italy
• ¹⁰Policlinico Tor Vergata, Rome, Italy
• ¹¹A.O.R.N. Cardarelli, Naples, Italy
• ¹²Oncology Unit, AULSS 2 Marca Trevigiana, Ca’ Foncello Hospital, Treviso, Italy
• ¹³Section of Oncology, Department of Engineering for Innovation Medicine (DIMI), University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy
• ¹⁴Ospedale San Luca, Lucca, Italy
• ¹⁵Oncology Department, Careggi University Hospital, Florence, Italy
• ¹⁶ASST Papa Giovanni XXIII, Bergamo, Italy
• ¹⁷Department of Precision Medicine in Medical, Surgical and Critical Care, AOUP Paolo Giaccone University Hospital, Palermo, Italy
• ¹⁸A.O. Papardo, Messina, Italy; current: Medical Oncology Department, Humanitas Istituto Clinico Catanese, 95045, Misterbianco, Catania, Italy
• ¹⁹Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072, Milan, Italy
• ²⁰Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
• ²¹Medical Oncology Division, ASST Sette Laghi, Varese, Italy
• ²²Dept. Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy
• ²³Università Vita-Salute San Raffaele, Milan, Italy
• ²⁴Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
• ²⁵Ospedale San Salvatore – Muraglia (PU), Pesaro Urbino, Italy
• ²⁶Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
• ²⁷Policlinico Universitario Campus Bio-Medico, Rome, Italy
• ²⁸SC Medical Oncology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
• ²⁹Department of Medicine, University of Milano-Bicocca, Milan, Italy
• ³⁰ASST GOM Niguarda, Milan, Italy
• ³¹AstraZeneca Italy, Milan, Italy
• ³²IQVIA Solutions Italy SRL, Modena, Italy
• ³³Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy

Background: Following the ADAURA study results, showing that adjuvant osimertinib was associated with significant improvement in disease-free survival among patients with stage IB-IIIA epidermal growth factor receptor mutation positive (EGFRm+) non-small cell lung carcinoma (NSCLC), an Early Access Program (EAP) was activated in Italy to provide preapproval access to osimertinib. Methods: The ELBA observational retrospective cohort study aims to describe the characteristics, diagnostic workup, mutation testing, and treatment patterns of the patients included in the ADAURA EAP. The retrospective observation period was from the day of the first procedure leading to the pathological diagnosis of NSCLC (index date) to osimertinib initiation and data were obtained from medical records or other original documents available at the sites. Results: Overall, 71 patients were evaluable, mainly females (73.2%), with mean (SD) age of 67.5 (8.7) years. Age-adjusted Charlson Comorbidity Index scored 2 or 3 for 74.7% of patients without considering lung cancer. Forty-six (66.7%) out of 69 evaluable patients with available data were discussed at the multi-disciplinary team meeting. The median (25th-75th percentiles) time from the initial diagnostic suspicion to the index date was 52.0 (30.0-67.0) days and from index date to EGFR test prescription 20.0 (0.0-42.0) days. Among patients with available data (N=69), the tests were mostly single-gene polymerase chain reaction mutation-specific test (63.8%) and next-generation sequencing (33.3%). Primary tumor surgery was mostly lobectomy (n/N=63/71, 88.7%). Pathological staging was IB for 21.1% of patients, II for 43.7% and III for 35.2%. Adjuvant chemotherapy prior to osimertinib was administered in 32.4% of patients. Osimertinib was started after a median (25th-75th percentiles) time from tumor resection of 2.9 (2.1-4.9) months. Conclusions: The ELBA Study showed an evolving landscape in biomarker-driven and molecular targeted therapies in early-stage NSCLC management towards the integration of mutational testing into clinical practice, with a growing focus on an optimal definition of adjuvant treatment.