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Are immune checkpoint inhibitors a valid option for papillary renal cell carcinoma? A multicentre retrospective study
Manon de Vries-Brilland1, Marine Gross-Goupil2, Valérie Seegers3
1Department of Medical Oncology, Integrated Centers of Oncology (ICO) Paul Papin, Angers, France.
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.
Insights
Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors showed limited effectiveness as a single treatment for metastatic papillary renal cell carcinoma (pRCC). Further research into combination therapies is needed for this patient group.
Area of Science:
- Oncology
- Immunotherapy
- Renal Cell Carcinoma
Background:
- Papillary renal cell carcinoma (pRCC) is the most common subtype of non-clear cell RCC (nccRCC).
- Previous studies on immune checkpoint inhibitors (ICIs) largely excluded nccRCC patients.
- This study focuses on the efficacy of PD-1/PD-L1 inhibitors in metastatic pRCC.
Purpose of the Study:
- To evaluate the activity and outcomes of PD-1/PD-L1 inhibitors in patients with metastatic pRCC.
- To assess treatment failure, response rates, survival, and adverse events associated with these therapies in pRCC.
Main Methods:
- Retrospective, multicenter study including 57 patients with pRCC.
- Analysis of time to treatment failure (TTF), objective response rate (ORR), overall survival (OS), and treatment-related adverse events (TRAEs).
- Patients received PD-1/PD-L1 inhibitors in various lines of treatment (1st, 2nd, or 3rd+).
Main Results:
- Median TTF was 3.1 months; median OS was 14.6 months.
- ORR showed 11% complete/partial response, 33% stable disease, and 56% progressive disease.
- Grade III-IV TRAEs occurred in 10% of patients, with no grade V events.
Conclusions:
- PD-1/PD-L1 inhibitors as monotherapy have limited activity in metastatic pRCC.
- This highlights an unmet need in pRCC treatment.
- Prospective trials investigating combination immunotherapies for pRCC are warranted.
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