Are immune checkpoint inhibitors a valid option for papillary renal cell carcinoma? A multicentre retrospective study.

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.

Informations de copyright

Copyright © 2020. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Conflict of interest statement M.G.-G. reports receiving honoraria from Ipsen, Janssen, Astellas Pharma; has served consultant or advisory role in Astellas Pharma, Janssen, Ipsen and MSD; reports receiving research funding from MSD, BMS, Janssen, Astra Zeneca, Pfizer and Roche and travel accommodation expenses from Amgen, MSD, Roche, Pfizer and Sanofi. B.B. has served consultant or advisory role in BMS; has been a member of the speaker's bureau of Pfizer and Ipsen; reports receiving research funding from Pfizer and BMS and travel and accommodation expenses from Pfizer. C.T. has served consulting or advisory role in BMS, Pfizer and Ipsen and reports receiving travel and accommodation expenses from Pfizer and Roche. C.C. has served consultant or advisory role in Pfizer, Novartis and BMS. P.B. has served consultant or advisory role in BMS, Pfizer, Roche, MSD, Ipsen, Novartis, and Sanofi and reports receiving honoraria from Astellas Pharma and travel and accommodation expenses from Amgen. S.N. reports receiving honoraria from Pfizer, Ipsen, BMS, EUSA Pharma and Novartis; research grant from Pfizer and travel expenses from BMS, Pfizer and Ipsen. D.B. has served consultant or advisory role in BMS, Ipsen and Pfizer and travel and accommodation expenses from Roche. O.H. reports receiving honoraria from BMS, AstraZeneca, Sanofi, Janssen and GSK and travel expense from Ipsen, Sanofi, Pfizer, Janssen and Astellas Pharma. L.G. has served consulting or advisory role in BMS, MSD, Novartis, Ipsen and Janssen. G.G. reports receiving travel expenses from BMS and Pfizer. A.T.-V. reports receiving honoraria from Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, BMS andRoche; has served consultant or advisory role in Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, BMS and Roche and reports receiving research funding from Pfizer and travel and accommodation expenses from BMS, Roche, Janssen and Pfizer. B.E. has served advisory role for BMS, Pfizer, Novartis, Roche, Ipsen, EUSA and Aveo and reports receiving travel grants from BMS and Pfizer and research grants from BMS, Novartis, Aveo and Pfizer. A.R. has served consultant or advisory role in Pfizer, BMS, AstraZeneca, Roche, MSD and Ipsen and reports receiving travel and accommodation expenses from Pfizer, BMS, AstraZeneca, Roche, MSD and Ipsen and institutional grant from Pfizer. L.A. has served consultant or advisory role in Pfizer, Novartis, BMS, Ipsen, Roche, MSD and AstraZeneca. M.de.V.-B., V.S., E.B., S.L., C.S. report no conflict of interest.