Recommendations for Treating Non–Clear Cell RCC


Pedro C. Barata, MD, MSc, discusses treatment options for patients with non–clear cell renal cell carcinoma.

Pedro C. Barata, MD, MSc, assistant professor of medicine at Tulane University School of Medicine, discusses treatment options for patients with non–clear cell renal cell carcinoma (RCC).

Non–clear cell histologies include papillary carcinoma, chromophobe, medullary, translocation-associated, and unclassified. According to Barata, there are data supporting some targeted therapies and immunotherapy (IO)-based regimens in non–clear cell RCC, though efficacy varies by histology.

The randomized phase 2 SWOG 1500/PAPMET trial (NCT02761057) established the efficacy of single-agent cabozantinib (Cabometyx) in metastatic papillary RCC with a median of 9.0 months progression-free survival (PFS) versus 5.6 months with sunitinib (Sutent). A phase 2 trial investigated the combination of cabozantinib with nivolumab (Opdivo) and showed a median PFS of 12.5 months in papillary, translocation-associated, or unclassified RCC, though patients with chromophobe histology did not benefit. The objective response rate (ORR) was 47.5% in the cohort that excluded those with chromophobe RCC. The cohort of patients with chromophobe RCC had a progressive disease rate of 14% compared with a stable disease rate of 71%.

Barata says he also favors an IO-based approach for these patients, with agents such as nivolumab and pembrolizumab (Keytruda) having some efficacy, but he prefers a combination with 2 mechanisms of action. He also stresses that clinical trials are important to offer patients better outcomes.


0:08 | There are convincing data, first with PAPMET that established cabozantinib as the new standard of care for patients with non–clear cell histology, referring specifically on papillary type 1 and type 2 RCC. But in addition to that, we had leverage on the cabozantinib establishing as a standard of care[because]we have data with cabozantinib plus nivolumab, not only papillary but other histologies—medullary, but also translocation and chromophobe. And it is true that the activity measured by response rate varies significantly. But look at the lack of progression with those. For instance, in those subtypes, in addition to the response rate for the cohort 1 response rate was [nearly] 50%. Even for cohort 2, progressive disease was low, and was 10% or less, which tells us or suggests that there's a good number of patients who can be well treated with these therapies.

1:09 | I tend to do an IO-based approach, because there's also molecular profiling data suggesting that a lot of these tumors do tend to respond to an IO-based approach. I tend not to do IO alone. [I’d] rather bring 2 different mechanisms of action before I actually consider cytotoxic chemotherapy that in some tumors, unfortunately, has very limited activity. But it's still considered because, unfortunately, these tumors tend to progress rapidly and fail the therapies we have available. So that's what I would say.

1:46 | But in addition to that, I should highlight the importance of clinical trials. Enroll patients with non–clear cell histologies in clinical trials because the outcomes of these patients are definitely not the same as clear cell histologies and we definitely need to do more. The best way to do that is to offer the medicine of the future and the only way to do that is through clinical trials enrolling these rarer RCC subtypes.

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