Lucio Crinò1, Giuseppe Bronte2, Paolo Bidoli3, Paola Cravero1, Elisa Minenza4, Enrico Cortesi5, Marina C Garassino6, Claudia Proto6, Federico Cappuzzo7, Francesco Grossi8, Giuseppe Tonini9, Maria Giuseppina Sarobba10, Graziella Pinotti11, Gianmauro Numico12, Riccardo Samaritani13, Libero Ciuffreda14, Antonio Frassoldati15, Marco Bregni16, Antonio Santo17, Francovito Piantedosi18, Alfonso Illiano18, Filippo De Marinis19, Stefano Tamberi20, Diana Giannarelli21, Angelo Delmonte1. 1. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 2. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. Electronic address: giuseppe.bronte@irst.emr.it. 3. Ospedale S. Gerardo, Monza, Italy. 4. AO Santa Maria, Terni, Italy. 5. Policlinico Umberto I, Rome, Italy. 6. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 7. AUSL della Romagna, Ravenna, Italy. 8. IRCCS AOU San Martino IST, Genova, Italy. 9. Policlinico Universitario Campus Biomedico, Rome, Italy. 10. ASL 3 S. Francesco, Nuoro, Italy. 11. Ospedale di Circolo e Fondazione Macchi, Varese, Italy. 12. AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy. 13. Presidio Nuovo Regina Margherita, Rome, Italy. 14. AOU Città della salute e della Scienza di Torino, Turin, Italy. 15. Arcispedale S. Anna, Ferrara, Ferrara, Italy. 16. Presidio Ospedaliero di Busto Arsizio, Varese, Italy. 17. AO Universitaria Integrata di Verona, Verona, Italy. 18. AO dei Colli, Monaldi- Cotugno-CTO, Naples, Italy. 19. European Institute of Oncology, Milan, Italy. 20. Degli Infermi Hospital, Faenza, Italy. 21. Regina Elena National Cancer Institute IRCCS, Rome, Italy.
Abstract
OBJECTIVES: Brain metastases are common among patients with non-squamous non-small-cell lung cancer (NSCLC) and result in a poor prognosis. Consequently, such patients are often excluded from clinical trials. In Italy an expanded access program (EAP) was used to evaluate nivolumab efficacy and safety in this subpopulation outside a clinical trial. MATERIALS AND METHODS: In this EAP, nivolumab was available for patients with non-squamous NSCLC in progression after at least one systemic treatment for stage IIIB/IV disease. Nivolumab 3 mg/kg was administered intravenously every 2 weeks. Patients with brain metastases could be included if they were asymptomatic, neurologically stable and either off corticosteroids or on a stable or decreasing dose of ≤10 mg/day prednisone. RESULTS: 409 out of 1588 patients included had asymptomatic or controlled brain metastases. A median of 7 doses (range 1-45) were delivered. Median follow-up was 6.1 months (range 0.1-21.9). The disease control rate was 39%: 4 patients had a complete response, 64 a partial response and 96 showed stable disease. At baseline, 118 patients were on corticosteroids and 74 were undergoing concomitant radiotherapy. The median overall survival in this subpopulation was 8.6 months (95% CI: 6.4-10.8). 337 discontinued treatment for various reasons, 23 (7%) of whom due to adverse events, in line with that observed in the overall population and in previous studies. CONCLUSIONS: Our results confirm that nivolumab is active in non-squamous NSCLC patients with brain metastases, despite their poor prognosis. Its safety profile is also concordant with results in the EAP overall population and in patients with other malignancies.
OBJECTIVES:Brain metastases are common among patients with non-squamous non-small-cell lung cancer (NSCLC) and result in a poor prognosis. Consequently, such patients are often excluded from clinical trials. In Italy an expanded access program (EAP) was used to evaluate nivolumab efficacy and safety in this subpopulation outside a clinical trial. MATERIALS AND METHODS: In this EAP, nivolumab was available for patients with non-squamous NSCLC in progression after at least one systemic treatment for stage IIIB/IV disease. Nivolumab 3 mg/kg was administered intravenously every 2 weeks. Patients with brain metastases could be included if they were asymptomatic, neurologically stable and either off corticosteroids or on a stable or decreasing dose of ≤10 mg/day prednisone. RESULTS: 409 out of 1588 patients included had asymptomatic or controlled brain metastases. A median of 7 doses (range 1-45) were delivered. Median follow-up was 6.1 months (range 0.1-21.9). The disease control rate was 39%: 4 patients had a complete response, 64 a partial response and 96 showed stable disease. At baseline, 118 patients were on corticosteroids and 74 were undergoing concomitant radiotherapy. The median overall survival in this subpopulation was 8.6 months (95% CI: 6.4-10.8). 337 discontinued treatment for various reasons, 23 (7%) of whom due to adverse events, in line with that observed in the overall population and in previous studies. CONCLUSIONS: Our results confirm that nivolumab is active in non-squamous NSCLCpatients with brain metastases, despite their poor prognosis. Its safety profile is also concordant with results in the EAP overall population and in patients with other malignancies.
Authors: Sarah B Goldberg; Kurt A Schalper; Scott N Gettinger; Amit Mahajan; Roy S Herbst; Anne C Chiang; Rogerio Lilenbaum; Frederick H Wilson; Sacit Bulent Omay; James B Yu; Lucia Jilaveanu; Thuy Tran; Kira Pavlik; Elin Rowen; Heather Gerrish; Annette Komlo; Richa Gupta; Hailey Wyatt; Matthew Ribeiro; Yuval Kluger; Geyu Zhou; Wei Wei; Veronica L Chiang; Harriet M Kluger Journal: Lancet Oncol Date: 2020-04-03 Impact factor: 41.316