Progress in the field of advanced non-clear cell renal cell carcinoma

This article from the NEJM meta-Journal (NEJM Journal Watch) Incremental Progress in Advanced Non-Clear-Cell Renal Cell Carcinoma with advanced non-transparent areas of cell renal cell carcinoma progression comment author: Robert Dreicer, MD, MS, MACP, FASCO in this 2 In the first phase of the study, cabozantinib (cabozantinib) showed benefits over sunitinib.

Papillary renal cell carcinoma (PRCC) is the most common histological subtype of non-clear cell renal cell carcinoma, accounting for approximately 15% of all renal cancers.

Patients whose histological examination results are non-clear cells are often excluded from large-scale phase 3 trials.
Therefore, clinicians lack prospective evidence and limited clinical experience when treating such patients.

There is evidence that molecular changes in the MET oncogene are associated with both type 1 and type 2 PRCC.
Based on this, the researchers conducted a randomized phase 2 trial to evaluate drugs with MET inhibitory properties.

In this open-label multicenter trial, 152 patients with metastatic PRCC were randomly assigned to receive savolitinib, crizotinib, cabozantinib, or sunitinib.

This study needs to be used to retrospectively assess the organization of PRCC subtypes.

The patient has received a systemic drug therapy, but it does not include vascular endothelial growth factor and MET-directed drugs.

The primary endpoint is progression-free survival (PFS).

The median age of the patients was 66 years, 54% had type 2 PRCC, and 61% were classified as intermediate-risk IMDC (International Metastatic Renal-Cell Carcinoma Database).

After completing the pre-determined invalidity analysis, the assignment of patients to the volitinib and crizotinib groups ceased; 44 patients were assigned to the cabozantinib group, and 46 patients were assigned to the sunitinib group.

The progression-free survival of the cabozantinib group was longer than that of the sunitinib group (median, 9.
0 months vs.
5.
6 months; hazard ratio, 0.
60).

The overall response rate in the cabozantinib group was also higher than that in the sunitinib group (23% vs.
4%).

Compared with sunitinib, there was no improvement in PFS after treatment with volitinib and crizotinib.

Grade 3 or 4 adverse events occurred in 69% of patients in the sunitinib group, 74% in the cabozatinib group, 37% in the crizotinib group, and 39% in the volitinib group.

The reviewers are commendable for conducting prospective studies on this rare disease.

Despite the limitations of the study design and scale, the researchers proved that cabozantinib has certain anti-cancer activity against PRCC, albeit with limited activity.

Cabozantinib should now be considered as a reference standard in future trials.

The reviewed article Pal SK et al.
A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: A randomised, open-label, phase 2 trial.
Lancet 2021 Feb 20; 397:695.
(https ://doi.
org/10.
1016/S0140-6736(21)00152-5) NEJM Journal Watch is published by NEJM Group.
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