At a median follow-up of 11 months, the median time to treatment failure was 6.7 months. Median progression-free survival was 7.0 months and median overall survival was 12.0 months.

No treatment-related deaths occurred. The most commonly occurring grade 3 adverse events were rash and palmar-plantar erythrodysesthesia (4%) and hypertension (4%).

The researchers also looked at next-generation sequencing data in 54 patients and found the most frequently altered somatic genes were CDKN2A (22%) and MET (20%). Responses were seen regardless of mutational status.

According to Dr Harshman, there are no biomarkers ready that have been prospectively validated to help predict which patients with non-clear cell RCC might respond to cabozantinib.

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“There has been work showing that c-Met–driven tumors, such as [those that] can be seen most frequently in papillary RCC, may respond better to drugs that target c-Met, such as cabozantinib,” Dr Harshman said. “Our series is one of the first to describe the response rates by the genomic makeup of the tumor albeit in a descriptive manner given the small numbers.”

In this study, the MET-altered tumors had response rates similar to what has been seen in clear cell disease and support targeting this pathway with agents such as cabozantinib.

In an editorial that accompanied the study, Paul Russo, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, wrote that this study should provide “clinicians with credible information that can guide treatment of these notoriously difficult tumors.”2

“Because of the rarity of these tumors, large-scale prospective trials that are successful in metastatic clear cell renal cell carcinoma will be difficult, if not impossible, to do. Yet, the determination of such a large group of oncologists to provide real-world care to their patients while obtaining and analyzing these data is truly remarkable,” Dr Russo wrote.

“Extending their work and organizational skills to more centers, awaiting the arrival of more effective systemic agents, and fine-tuning drug selection based on genomics and other biomarkers might allow these investigators the opportunity for future and increasingly effective attempts to tackle these particularly lethal forms of kidney cancer.”


  1. Chanza NM, Xie W, Bilen MA, et al. Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study [published online February 28, 2019]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30907-0
  2. Russo P. A well organized effort to metastatic non-clear-cell renal cell carcinoma [published online February 28, 2019]. Lancet Oncol. doi:10.1016/S1470-2045(19)30036-1