Retrospective Data Show Nephrectomy With Immune-Targeted Therapy Offers Potential PFS Benefit in Metastatic RCC

Nephrectomy with immune-targeted therapy was associated with a progression-free survival (PFS) benefit compared with immunotherapy alone in patients with metastatic renal cell carcinoma (mRCC), according to findings from a retrospective study conducted in China published in BMC Cancer.

At a median follow-up of 29.3 months (95% CI, 28.5-30.2), patients with mRCC who underwent nephrectomy and immune-targeted therapy (n = 97) achieved a median PFS of 14.4 months (95% CI, 12.6-16.2) compared with 10.8 months (95% CI, 8.3-13.3) among patients who were treated with immunotherapy alone (n = 68; HR, 0.476; 95% CI, 0.323-0.701; P = .0002). Moreover, the 12-month PFS rates in the nephrectomy and non-nephrectomy groups were 60.8% vs 30.9%, respectively; the 18-month PFS rates were 25.8% vs 7.4%, respectively.

“The expression of immune response target factors, such as CTLA-4, B7-H1, B7-H3, B7-H4, and PD-1 on the surface of tumor cells and effector T cells can be negatively regulated by immunosuppressive factors and cells, resulting in immune escape [of tumor cells],” investigators wrote. “Therefore, primary renal tumor resection reduces the burden of immunosuppressive factors and cells, enhances the immune response.”

The multicenter, retrospective study examined patients with mRCC who received a combination of targeted and immunotherapy from May 17, 2019, to August 1, 2022, at 3 centers in China: The First Affiliated Hospital of Nanchang University, Jiangxi Cancer Hospital, and Jiangxi Provincial People’s Hospital. All patients had received targeted combination immunotherapy for a minimum of 2 cycles. In order to be included in the study, patients had to be at least 18 years of age with a pathologic diagnosis of metastatic RCC, have a life expectancy greater than 1 month, and an ECOG performance status of 2 or less.

Investigators screened a total of 207 patients, of which 42 were excluded. Patients were excluded due to double primary tumors (n = 6), renal pelvic carcinoma (n = 8), poor performance status (n = 7), renal soft tissue tumors (n = 8), and incomplete medical records (n = 13). Patients in the nephrectomy group were subdivided into those who received radical nephrectomy (n = 58) or cytoreductive nephrectomy (n = 39).

The primary end point was PFS. Secondary end points included objective response rate (ORR) and adverse effects (AEs).

The baseline patient characteristics were well balanced between the nephrectomy and non-nephrectomy groups; the median age was 59 years (range, 26-84) vs 59 years (range, 19-86), respectively. Most patients in both groups were men (71.1% vs 67.6%), had an ECOG performance status of 1 (88.7% vs 80.9%), had clear cell carcinoma (83.5% vs 82.4%), and had a moderate risk International mRCC Database Consortium (IMDC) grade (62.9% vs 69.1%).

In the nephrectomy and non-nephrectomy arm, patients were on their first (55.7% vs 63.2%, respectively), second (29.9% vs 22.1%), third (11.3% vs 11.8%), or at least fourth (3.1% vs 2.9%) line of immune-targeted therapy. In terms of specific targeted agents, patients received axitinib (Inlyta; 45.4% vs 44.1%), lenvatinib (Lenvima; 6.2% vs 16.2%), anlotinib (AL3818; 10.3% vs 11.8%), or other drugs (38.1% vs 27.9%).

Additional findings from the study demonstrated that most patients in the nephrectomy (82.5%) and non-nephrectomy (82.4%) groups experienced progressive disease (PD). Patients died at a rate of 44.3% vs 50% respectively, conferring an overall survival (OS) maturity of 46.7%; all deaths were due to PD.

Available survival data showed that the median OS in the nephrectomy group was 28.9 months (95% CI, 25.2-32.6) compared with 17.1 months (95% CI, 13.7-20.5) in the non-nephrectomy group (HR, 0.395; 95% CI, 0.235-0.664; P = .0005). The 12-month OS rates were 77.3% vs 58.8%, respectively, and the 18-month rates were 46.4% vs 20.6%, respectively.

The ORR in the nephrectomy group was 60.8%, including 1 patient who achieved a complete response, compared with 52.9% in the non-nephrectomy group. The respective disease control rates were 83.5% vs 75% (P = .179). The stable disease rates were 22.7% vs 22.1%, respectively.

Due to the lack of OS maturity, investigators only performed a PFS subgroup analysis. Findings from the analysis revealed that PFS favored patients who underwent nephrectomy in every subgroup that was examined. The subgroups with the most pronounced benefit were those with a WHO/ISUP score of 4 (HR, 0.177; 95% CI, 0.024-1.286), those with a poor IMDC risk profile (HR, 0.220; 95% CI, 0.094-0.515), and an ECOG performance status of 2 (HR, 0.346; 95% CI, 0.069-1.730).

Regarding safety, the most common any-grade treatment-related AEs (TRAEs) in the nephrectomy group consisted of hypothyroidism (18.6%), drug-induced kidney injury (16.5%), rash (14.4%), and drug-induced liver injury (10.3%). In the non-nephrectomy group, any-grade TRAES included hypothyroidism (22.1%), pneumonia (13.2%), and drug-induced kidney injury (8.8%). Grade 3/4 TRAEs were rare in both the nephrectomy and non-nephrectomy groups; patients in both groups experienced grade 3 or higher hypothyroidism (2.1% vs 1.5%) and pneumonia (2.1% vs 2.9%).

Investigators noted that their study was limited by its non-randomized, retrospective nature, and relatively small sample size. Additionally, heterogeneity was observed between the nephrectomy and non-nephrectomy arms in terms of immune-targeted agents, and response depth was not evaluated due to lack of data. Longer follow-up would provide a clearer definition of outcomes, they said.

“Nephrectomy may provide PFS benefit with tolerable safety for patients with advanced renal cell carcinoma who receive immune-targeted therapy. In multivariate analysis, nephrectomy, clear cell carcinoma, and oligo-organ metastasis were found to be favorable independent prognostic factors,” study authors wrote in conclusion.

Reference

Dong H, Cao Y, Jian Y, et al. Patients with metastatic renal cell carcinoma who receive immune-targeted therapy may derive survival benefit from nephrectomy. BMC Cancer. 2023;23(1):943. doi:10.1186/s12885-023-11408-x