Laurent Dercle1, Samy Ammari2, Stéphane Champiat2, Christophe Massard2, Charles Ferté2, Lokmane Taihi3, Romain-David Seban3, Sandrine Aspeslagh2, Linda Mahjoubi2, Nyam Kamsu-Kom4, Caroline Robert4, Aurélien Marabelle5, Martin Schlumberger6, Jean-Charles Soria7, Sophie Postel-Vinay7. 1. Gustave Roussy, Université Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif, F-94805, France; Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, F-94805, France. Electronic address: laurent.dercle@gustaveroussy.fr. 2. Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France. 3. Gustave Roussy, Université Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif, F-94805, France. 4. Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Department of Medical Oncology, Villejuif, F-94805, France. 5. Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, F-94805, France; Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France. 6. Gustave Roussy, Université Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif, F-94805, France; Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, F-94805, France. 7. Université Paris-Saclay, Paris, France; Gustave Roussy, Université Paris-Saclay, Drug Development Department, Villejuif, F-94805, France; Gustave Roussy, Université Paris-Saclay, INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Villejuif, F-94805, France.
Abstract
BACKGROUND: Drugs targeting programmed death receptor-1 (PD-1) and its ligand PD-L1 have shown activity in multiple malignancies. Considering their novel mechanism of action, whether traditional prognostic scores also apply to patients treated with these drugs is unknown. We investigated whether a baseline 3-point (pt) computed tomography (CT) scan (PS3-CT) score and a 7-pt prognostic (PS7) score allowed identifying long-term survivors on anti-PD-1/-L1 therapy. MATERIALS AND METHODS: We reviewed 251 consecutive patients enrolled in phase I trials evaluating anti-PD-1/-L1 agents between 26th December 2011 and 7th September 2015. PS3-CT was calculated using high tumour burden (TB1D-RECIST > 9 cm), low skeletal muscle index (SMI < 53 cm(2) m(-2)) and non-pulmonary visceral metastases (NPVM) (1 pt each). PS7 was calculated by adding lower performance status, decreased serum albumin, increased serum lactate dehydrogenase and more than two distant metastases (1 pt each). Effect on overall survival (OS) of each parameter was tested using Kaplan-Meier and multivariable Cox analyses. RESULTS: PS3-CT was a significant independent predictor of OS (hazard ratio [HR] = 1.39 [95% confidence interval {CI} = 1.07-1.81], p = 0.01) when compared to the Royal Marsden Hospital, Barbot and American Joint Committee on Cancer scores. High TB (n = 78), low SMI (n = 55) and NPVM (n = 146) were associated with poorer survival (p < 0.01). High TB and low SMI were independent predictors of OS (respective HR of death: 2.00 [95% CI = 1.38-2.88], p < 0.01 and 1.75 [95% CI = 1.15-2.66], p < 0.01). PS7 was a significant predictor of OS (HR = 1.40 [95% CI = 1.25-1.56], p < 0.01). CONCLUSION: Objective and rapid-risk scoring based on three CT scan parameters allows identifying patients with prolonged OS on anti-PD-1/-L1 therapy, independently from conventional clinical-biological prognostic scores.
BACKGROUND: Drugs targeting programmed death receptor-1 (PD-1) and its ligand PD-L1 have shown activity in multiple malignancies. Considering their novel mechanism of action, whether traditional prognostic scores also apply to patients treated with these drugs is unknown. We investigated whether a baseline 3-point (pt) computed tomography (CT) scan (PS3-CT) score and a 7-pt prognostic (PS7) score allowed identifying long-term survivors on anti-PD-1/-L1 therapy. MATERIALS AND METHODS: We reviewed 251 consecutive patients enrolled in phase I trials evaluating anti-PD-1/-L1 agents between 26th December 2011 and 7th September 2015. PS3-CT was calculated using high tumour burden (TB1D-RECIST > 9 cm), low skeletal muscle index (SMI < 53 cm(2) m(-2)) and non-pulmonary visceral metastases (NPVM) (1 pt each). PS7 was calculated by adding lower performance status, decreased serum albumin, increased serum lactate dehydrogenase and more than two distant metastases (1 pt each). Effect on overall survival (OS) of each parameter was tested using Kaplan-Meier and multivariable Cox analyses. RESULTS:PS3-CT was a significant independent predictor of OS (hazard ratio [HR] = 1.39 [95% confidence interval {CI} = 1.07-1.81], p = 0.01) when compared to the Royal Marsden Hospital, Barbot and American Joint Committee on Cancer scores. High TB (n = 78), low SMI (n = 55) and NPVM (n = 146) were associated with poorer survival (p < 0.01). High TB and low SMI were independent predictors of OS (respective HR of death: 2.00 [95% CI = 1.38-2.88], p < 0.01 and 1.75 [95% CI = 1.15-2.66], p < 0.01). PS7 was a significant predictor of OS (HR = 1.40 [95% CI = 1.25-1.56], p < 0.01). CONCLUSION: Objective and rapid-risk scoring based on three CT scan parameters allows identifying patients with prolonged OS on anti-PD-1/-L1 therapy, independently from conventional clinical-biological prognostic scores.
Authors: Romain-David Seban; John S Nemer; Aurélien Marabelle; Randy Yeh; Eric Deutsch; Samy Ammari; Antoine Moya-Plana; Fatima-Zohra Mokrane; Robyn D Gartrell; Grace Finkel; Luke Barker; Amélie E Bigorgne; Lawrence H Schwartz; Yvonne Saenger; Caroline Robert; Laurent Dercle Journal: Eur J Nucl Med Mol Imaging Date: 2019-07-25 Impact factor: 9.236
Authors: Laetitia Vercellino; Dorine de Jong; Roberta di Blasi; Salim Kanoun; Ran Reshef; Lawrence H Schwartz; Laurent Dercle Journal: Front Oncol Date: 2021-05-28 Impact factor: 6.244