Immunotherapy Prior to Development of Brain Metastases Improves Survival in Metastatic RCC

Treatment with immunotherapy prior to the development of brain metastases improved the median overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC), according to findings from a retrospective study presented at the 2022 ESMO Congress.

Data showed that patients with RCC who received immunotherapy prior to the diagnosis of brain metastases (n = 32) experienced a median OS that was not yet reached (NR; 95% CI, 18.0-NR) compared with 13.7 months (95% CI, 9.2-28.6) in those who were administered immunotherapy after they were diagnosed with brain metastases (n = 54) and 10.8 months in those with brain metastases who did not receive immunotherapy at any point (95% CI, 7.5-16.7; P = .0098).

“There is a strong argument for the use of immunotherapy as first-line systemic [treatment] to improve median OS in patients who develop brain metastases,” lead study author Gihan Ratnayake, MD, of Taunton and Somerset NHS Foundation Trust in Taunton, United Kingdom, and colleagues, wrote in a poster presentation of the data.

The presence of brain metastases has historically been linked with worse outcomes for patients with metastatic RCC. With the retrospective study, investigators in the United Kingdom (UK) sought to perform an individual case review of outcomes in patients with mRCC and brain metastases in the era of immunotherapy.

To do this, they collected data on 1173 patients who began first-line systemic treatment between January 1, 2018, and June 30, 2021, at 15 centers in the United Kingdom. Data were gathered on brain metastases, International Metastatic RCC Database Consortium (IMDC) risk scores, systemic therapies, and local therapies. Median OS data were evaluated using Kaplan-Meier analyses.

Of the 1173 patients, 13.1% (n = 154) were identified to have brain metastases; 80% of these patients were symptomatic at the time that those metastases were diagnosed. “In our series, there is a greater incidence of brain metastases in [patients with] mRCC than with historical data,” the study authors noted.

At data cutoff, 105 patients had less than 6 months of follow-up from their diagnosis of metastatic disease, 405 patients had less than 1 year of follow-up, and 676 patients had less than 2 years of follow-up.

Overall, 225 patients (19.2%) underwent brain imaging within 3 months of the start of first-line systemic therapy, leading to the diagnosis of brain metastases in 26 patients. Twenty-eight of 245 patients (11.4%) who underwent brain imaging within 3 months of diagnosis had brain metastases.

Among patients with brain metastases, the median age was 62 years, and 71.43% were male. Most patients underwent nephrectomy (n = 87), had clear cell histology (87.01%), and did not have sarcomatoid features (72.73%). Additionally, 50.65% of patients received 1 line of therapy, 34.42% had 2 lines, 11.04% received 3 lines, and 3.9% received 4 lines. No patients received 5 or more lines of treatment. Most patients with brain metastases underwent first-line therapy that included a TKI (n = 108), double-agent immunotherapy (n = 35), immunotherapy plus a TKI (n = 8), and single-agent immunotherapy (n = 3).

Regarding IMDC risk group, 12.99% had favorable risk, 59.09% had intermediate risk, 24.68% had poor risk, and 3.25% had missing information. Site of metastases included adrenal (14.94%), lung (79.22%), liver (10.39%), bone (28.57%), pancreatic (4.55%), nodal (38.31%), and other (11.69%). Furthermore, 5.84% had only brain metastases, 33.77% had 1 additional metastatic site, 35.06% had 2 additional sites, 17.53% had 3 additional sites, and 7.79% had 4 additional sites.

Fifty-two percent of patients with brain metastases were diagnosed prior to the start of first-line therapy; 31% were diagnosed before second-line therapy, 13% before third-line therapy, and 4% before fourth-line therapy. Following the diagnosis of brain metastases, 44 patients received no subsequent lines of systemic therapy, 79 patients had 1 additional line, 24 patients were given 2 additional lines, and 7 patients received 3 additional lines.

Thirty-two percent of patients with brain metastases received local therapy, including stereotactic radiosurgery, neurosurgery plus other local therapy, neurosurgery alone, whole brain radiation therapy, and stereotactic radiosurgery plus whole brain radiation therapy.

Additional data showed that the median OS was 21.03 months for all patients with mRCC and brain metastases from the start of first-line therapy, and 14.30 months from the diagnosis of brain metastases.

Among patients with brain metastases, those with favorable-risk disease experienced a median OS of 65.8 months, 31.7 months in those with intermediate-risk disease, and 24.1 months in those with poor-risk disease.

Among all patients with RCC, the median OS for those with favorable-risk, intermediate-risk, and poor-risk disease was 33.8 months, 26.7 months, and 20.9 months, respectively. In those without brain metastases who had favorable-, intermediate-, and poor-risk disease, the median OS was 30.7 months, 25.3 months, and 20.3 months, respectively.

“Identifying brain metastases is important with modern local therapy and better systemic therapy to help improve long-term outcomes in this cohort, suggesting more routine brain imaging is important,” the study authors concluded. “More mature data will be collected in this cohort.”

Reference

Ratnayake G, Challapalli A, McGrane J, et al. A UK multicentre retrospective review of metastatic renal cell carcinoma (mRCC) patients (pts) outcomes with brain metastases (BM) in the modern era. Ann Oncol. 2022;33(suppl 7):S660-S680. doi:10.1016/annonc/annonc1072