A Costantini1, V Fallet1, J Corny2, S Friard3, C Chouaid4, B Duchemann5, E Giroux-Leprieur6, L Taillade7, L Doucet8, S Brosseau9, M Wislez1, J Tredaniel2, J Cadranel10. 1. AP-HP, Hôpital Tenon et Sorbonne Université, 4 Rue de la Chine 75020, Paris, France. 2. Hôpital Saint-Joseph, 185 Rue Raymond Losserand 75014, Paris, France. 3. Hôpital Foch, 40 Rue Worth 92151, Suresnes, France. 4. Centre Hospitalier Intercommunal de Créteil, 40 Avenue de Verdun 94000, Créteil, France. 5. AP-HP, Hôpital Avicenne, 125 Rue de Stalingrad 93000, Bobigny, France. 6. AP-HP, Hôpital Ambroise Pare, 9 Avenue Charles de Gaulle 92100, Boulogne-Billancourt, France. 7. AP-HP, Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l'hôpital 75013, Paris, France. 8. AP-HP, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux 75010, Paris, France. 9. AP-HP, Hôpital Bichat, 46 Rue Henri Huchard 75018, Paris, France. 10. AP-HP, Hôpital Tenon et Sorbonne Université, 4 Rue de la Chine 75020, Paris, France. Electronic address: jacques.cadranel@aphp.fr.
Abstract
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionised cancer care especially in lung cancer. New response patterns have been described under ICIs such as pseudo-progression or hyper-progressive disease (HPD). The definition of HPD is yet to be consensual. The aim of this study was to suggest a clinical definition of nivolumab-refractory patients and find factors associated with this entity. METHODS: We performed a multi centric retrospective study including all patients who received nivolumab for the treatment of advanced non-small cell lung cancer (NSCLC) during the French authorisation for temporary use in 2015. RESULTS: 303 patients were included in the cohort and 292 had details on the number of nivolumab injections received. 57 patients (20%) were nivolumab-refractory. These patients had worse PS at nivolumab initiation (p < 0.0001), shorter duration of treatment before nivolumab (p = 0.028) and had dramatically shorter nivolumab overall survival (p < 0.0001) than patients who did not present with refractory disease. CONCLUSION: Nivolumab-refractory disease can affect up to 20% of patients treated with nivolumab for advanced NSCLC with dramatically shortened survival rates. Further studies are needed to understand the precise mechanisms leading to refractory disease as well as its management.
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionised cancer care especially in lung cancer. New response patterns have been described under ICIs such as pseudo-progression or hyper-progressive disease (HPD). The definition of HPD is yet to be consensual. The aim of this study was to suggest a clinical definition of nivolumab-refractory patients and find factors associated with this entity. METHODS: We performed a multi centric retrospective study including all patients who received nivolumab for the treatment of advanced non-small cell lung cancer (NSCLC) during the French authorisation for temporary use in 2015. RESULTS: 303 patients were included in the cohort and 292 had details on the number of nivolumab injections received. 57 patients (20%) were nivolumab-refractory. These patients had worse PS at nivolumab initiation (p < 0.0001), shorter duration of treatment before nivolumab (p = 0.028) and had dramatically shorter nivolumab overall survival (p < 0.0001) than patients who did not present with refractory disease. CONCLUSION:Nivolumab-refractory disease can affect up to 20% of patients treated with nivolumab for advanced NSCLC with dramatically shortened survival rates. Further studies are needed to understand the precise mechanisms leading to refractory disease as well as its management.