Manon de Vries-Brilland1, Marine Gross-Goupil2, Valérie Seegers3, Elouen Boughalem1, Benoit Beuselinck4, Constance Thibault5, Christine Chevreau6, Sylvain Ladoire7, Philippe Barthélémy8, Sylvie Negrier9, Delphine Borchiellini10, Olivier Huillard11, Lionnel Geoffrois12, Gwenaelle Gravis13, Carolina Saldana14, Antoine Thiery-Vuillemin15, Bernard Escudier16, Alain Ravaud2, Laurence Albiges17. 1. Department of Medical Oncology, Integrated Centers of Oncology (ICO) Paul Papin, Angers, France. 2. Department of Medical Oncology, Hôpital Saint-André, University of Bordeaux-CHU, Bordeaux, France. 3. Biostatistics Department, Integrated Centers of Oncology (ICO) Paul Papin, Angers, France. 4. University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. 5. European George Pompidou Hospital, Paris, France. 6. IUCT-Oncopôle Institut Claudius Regaud, Toulouse, France. 7. Department of Medical Oncology, Center GF Leclerc, Dijon, France. 8. Medical Oncology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 9. Centre Léon Bérard, Lyon, France. 10. Centre Antoine Lacassagne, Nice, France. 11. Cochin Hospital, Paris Descartes University, AP-HP, CARPEM, Immunomodulatory Therapies Multidisciplinary Study Group, Paris, France. 12. Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandœuvre-Lès-Nancy, France. 13. Medical Oncology, Institut Paoli-Calmettes, Marseille, France. 14. Oncology Department, Hôpital Henri Mondor, APHP, Créteil, France. 15. CU-PH Medical Oncology, Besancon, France. 16. Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 17. Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address: laurence.albiges@gustaveroussy.fr.
Abstract
BACKGROUND: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). Pivotal studies evaluating immune checkpoint inhibitors mostly excluded nccRCC. The aim of this retrospective and multicentre study was to evaluate the activity of programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors specifically in metastatic pRCC. METHODS: The primary end-point was time to treatment failure (TTF). Secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: From 02/2016 to 01/2019, 57 patients with pRCC were included. Histology included 16 (28%) type 1 pRCC, 34 (60%) type 2 pRCC and 7 (12%) unclassified pRCC. Treatment with immune checkpoint inhibitors was used in the first-line setting in 4 patients (7%), in the second-line setting in 32 patients (56%) and in the third-line setting or more in 21 patients (37%). With a median follow-up of 12 months (95% confidence interval [CI]: 9.9-21.0), the median TTF was 3.1 months (95% CI: 2.7-5.0). Among the 55 patients evaluable for ORR, best response was complete response/partial response in 6 patients (11%), stable disease in 18 patients (33%) and progressive disease in 31 patients (56%). The median OS was 14.6 months (95% CI: 9.0- not reached). TRAEs of grade III-IV were noted in 6 patients (10%) leading to treatment discontinuation, and no grade V TRAEs were observed. CONCLUSION: PD-1/PD-L1 inhibitors exhibit limited activity as monotherapy in this pRCC population, which remains an unmet need. Our findings underline the need for further prospective clinical trials evaluating immune checkpoint inhibitor combinations in patients with pRCC.
BACKGROUND:Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). Pivotal studies evaluating immune checkpoint inhibitors mostly excluded nccRCC. The aim of this retrospective and multicentre study was to evaluate the activity of programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors specifically in metastatic pRCC. METHODS: The primary end-point was time to treatment failure (TTF). Secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: From 02/2016 to 01/2019, 57 patients with pRCC were included. Histology included 16 (28%) type 1 pRCC, 34 (60%) type 2 pRCC and 7 (12%) unclassified pRCC. Treatment with immune checkpoint inhibitors was used in the first-line setting in 4 patients (7%), in the second-line setting in 32 patients (56%) and in the third-line setting or more in 21 patients (37%). With a median follow-up of 12 months (95% confidence interval [CI]: 9.9-21.0), the median TTF was 3.1 months (95% CI: 2.7-5.0). Among the 55 patients evaluable for ORR, best response was complete response/partial response in 6 patients (11%), stable disease in 18 patients (33%) and progressive disease in 31 patients (56%). The median OS was 14.6 months (95% CI: 9.0- not reached). TRAEs of grade III-IV were noted in 6 patients (10%) leading to treatment discontinuation, and no grade V TRAEs were observed. CONCLUSION:PD-1/PD-L1 inhibitors exhibit limited activity as monotherapy in this pRCC population, which remains an unmet need. Our findings underline the need for further prospective clinical trials evaluating immune checkpoint inhibitor combinations in patients with pRCC.
Authors: Ana Filipa Palma Dos Reis; Diana Simão; Thomas Odeny; Chiara Rodrigues; Mário Fontes-Sousa; Ricardo da Luz; Rajasree Pia Chowdry; Sarah J Welsh; Channing Paller; Pedro C Barata Journal: Kidney Cancer Date: 2022-08-04