Papillary renal cell carcinoma (PRCC) is the second most common subtype of renal carcinoma accounting for approximatively 10-15% of all renal cancers. Different types of PRCC have been described on the basis of two histologic subtypes, type 1 in 25 to 30% cases, and type 2, with a worse prognosis reported for type 2 metastatic disease. There is currently no standard of care specifically dedicated to metastatic PRCC patients (mPRCC) and treatments developed for metastatic clear cell carcinomas are commonly used ; therefore, mPRCC enrollment in clinical trials is encouraged.~Clinical trials investigated treatments such as sunitinib, or everolimus approved for advanced clear cell carcinoma, or the dual kinase inhibitor directed both towards VEGF receptors (VEGFr) and the MET pathway foretinib, or more recently, the selective MET inhibitor savolitinib. Response rates (RR) were disappointing since generally below 15%, except in a subset of patients with MET germline alterations.~Axitinib which is indicated as second-line treatment in advanced clear cell carcinoma was investigated in a recent specific trial : the Axipap trial. This multicentric phase II trial was conducted after central pathology review to confirm the histologic subtype and a central review was performed to assess the primary endpoint : the 24 week progression free rate (24wPFR). With a median follow up time of 30 months this 24wPFR was found to be over 45%. The best response rate was 28.6% according to the investigators with a median duration of response near 8 months. The investigator assessed response rate was 35.7% in the type 2 subgroup indicating a more important effect of anti-VEGFr in this subtype than in the type 1. The median PFS was around 6 months and was virtually identical in both subtypes.~Recently, some preliminary results of the use of Immune Checkpoint Inhibitors in metastatic non clear cell carcinoma were made available. The PD1 directed antibody Pembrolizumab showed a 28% response rate in 118 patients with papillary tumors including a 6% complete remission rate ; the median duration of response was of 15.3 [2.8-21.0+] months. Atezolizumb (anti-PDL1) combined with Bevacizumab and Durvalumab (anti-PDL1) combined with savolitinib (Met directed TKI) obtained response rates in the same range. These preliminary results demonstrated the potential interest of combining axitinib with an immune check point inhibitor. The results of pembrolizumab as monotherapy were obtained in the largest subset with mPRC.~According to these results obtained, the combination of axitinib and pembrolizumab seems promising in type 2 papillary tumors.
Multicenter Phase II Study of Axitinib +/- Pembrolizumab in First Line Treatment for Patients With Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (PRCC)