Although high-dose IL-2 is currently the only potentially curative therapy in RCC, Dr Rini told Cancer Therapy Advisor that nivolumab “certainly has the potential” to be curative, but more long-term follow-up data are needed to determine if that is the case. The optimal role of nivolumab is likely to continue to evolve; the CheckMate 2014 study (NCT02231749) of nivolumab in combination with ipilimumab vs sunitinib is ongoing in the first-line setting, with final results expected in 2019.


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Although the combination of 2 targeted agents in RCC has resulted primarily in substantial toxicity, a new approach is to combine a targeted agent with immunotherapy. Such a combination “does not appear to be too toxic, at least based on the early data returns,” said Dr Rini. The RAPID study (NCT02420821) of atezolizumab, an anti-PD-L1 antibody, and bevacizumab vs atezolizumab or sunitinib alone is ongoing, with final results expected in 2020.

Agent selection remains a challenge. According to Dr Rini, selection is frequently based on the physician’s experience. In addition, the review by Motzer and colleagues [JG1] highlighted 5 factors demonstrated to be independent predictors of PFS with sunitinib: serum lactate dehydrogenase (LDH), 2 or more metastatic sites, no previous nephrectomy, Eastern Cooperative Oncology Group (ECOG) performance status, and baseline platelet count.

Independent predictors of OS with sunitinib are serum LDH, corrected serum calcium level, time from diagnosis to treatment, hemoglobin level, ECOG performance status, and bone metastases. Prognostic risk group, as determined by the MSKCC or the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models can help identify patients who may benefit from sunitinib.

RELATED: Age Correlates With Incidence of RCC Among Pediatric Patients With Renal Malignancy

Although there was hope that biomarkers may aid in treatment selection, research efforts to date have not yielded a viable option. “We’ve been looking for over 10 years for biomarkers and haven’t found them, so it’s probably unlikely that it’s going to happen at this point, at least for the TKIs,” Dr Rini said.

Reference

  1. Motzer RJ, Escudier B, Gannon A, Figlin RA. Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma. Oncologist. 2016 Nov 2. doi: 10.1634/theoncologist.2016-0197 [Epub ahead of print]