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14-11-2022 | Renal cell carcinoma | News

Second-line metastatic RCC outcomes similar regardless of first-line immunotherapy combo partner

Author: Shreeya Nanda


medwireNews: Among patients with metastatic clear cell renal cell carcinoma (RCC), the outcomes of second-line treatment are similar irrespective of whether they received dual immunotherapy (IO) or IO plus a tyrosine kinase inhibitor (TKI) in the first line, indicates a chart review.

“Without a biomarker-based stratification system, physicians recommend IO/IO versus TKI/IO based on clinical factors including tumor histology, risk group, comorbid conditions, and patient preference,” say Chung-Han Lee and colleagues, from the Memorial Sloan Kettering Cancer Center in New York, USA.

These study findings suggest “that such individualized clinical stratification is an appropriate method for assigning patients to first-line therapy, until a predictive biomarker differentiating IO/IO from TKI/IO responders becomes available,” they continue.

The researchers identified 173 patients who received first-line dual IO (n=90) or TKI plus IO (n=83) for metastatic clear cell RCC at their institution between January 2014 and December 2020. All patients in the dual IO group received nivolumab plus ipilimumab, while the most common regimens in the TKI plus IO group were axitinib plus pembrolizumab (34%), lenvatinib plus pembrolizumab (29%), and axitinib plus avelumab (25%).

Lee et al highlight that although the dual IO and TKI plus IO groups were comparable with regard to certain baseline factors such as age (median 58 years in both), a significantly higher proportion of patients in the former group had brain metastases (8.9 vs 0.0%) and an intermediate or poor IMDC risk score (88.0 vs 68.0%), whereas a lower proportion had undergone nephrectomy (67.0 vs 86.0%).

The most common second-line treatment in both the dual IO and TKI plus IO groups was TKI alone, used by a respective 78% and 67% of patients, followed by TKI plus IO in the former group, at 19%, and IO alone in the latter, at 27%.

Kaplan–Meier analysis showed no significant difference between patients who received first-line dual IO or TKI plus IO in terms of the endpoint of progression-free survival on next-line therapy (PFS-2) – defined as the time from initiation of first-line therapy to second objective disease progression or death from any cause. The median PFS-2 times were 23 and 44 months, respectively.

The median overall survival (OS) times were likewise similar, at 50 months for the dual IO group and 56 months for the TKI plus IO group.

The results were confirmed by restricted mean survival time analysis adjusted for propensity score, in which the PFS-2 estimates were 30 months for people who received first-line dual IO and 33 months for those given TKI plus IO, while the corresponding OS estimates were 37 and 38 months.

However, the response to second-line therapy was significantly better among participants treated with dual IO rather than TKI plus IO in the first line, at rates of 47% versus 13%.

“These findings do not support a change in current utilization practices for IO/IO and TKI/IO treatment strategies in [clear cell] RCC,” summarize the researchers in European Urology.

And they conclude: “Further research would be required to demonstrate overall superiority or noninferiority of either approach; alternatively, biomarker discovery initiatives would help refine clinical applications of these therapeutic strategies in molecularly selected patient groups.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Eur Urol 2022; doi:10.1016/j.eururo.2022.10.017