GU Cancers 2021 | Bevacizumab plus erlotinib for RMC

With regards to this regimen bevacizumab plus erlotinib in RMC. RMC is renal medullary carcinoma and it’s abbreviated as RMC. And it is one of the deadliest kidney cancers and it almost exclusively afflicts individuals with sickle cell trait, usually young people of African descent, African Americans in the US. And it’s a deadly disease with a very short overall survival, that back in 2017, in a retrospective analysis, was about 13 months despite our best treatment regimens.

And so what happened in the interim is that when our group performed a comprehensive molecular characterization of this malignancy, multiple samples and analyze at the transcriptomic level and genomic level, we found that RMC has certain distinct metabolic features. And some of these metabolic features are in common with another rare kidney malignancy called fumarate hydratase-deficient renal cell carcinoma, or FHRCC, which often is part of a syndrome called hereditary leiomyomatosis and renal cell carcinoma, HLRCC.

And what’s happened is that we’ve known for the last few years through work pioneered by the NCI that bevacizumab and erlotinib, that combination can target metabolic pathways in HLRCC and fumarate hydratase-deficient renal cell carcinoma, very efficiently, and it can cause profound responses in this disease. So, we found that since we were seeing these commonalities at the molecular level this might be a worthwhile regimen to start testing. And so we indeed started using this regimen predominantly in patients who were heavily pretreated, so most of them didn’t have any other options and we did see responses.

So, we tested this regimen and we analyzed the data retrospectively using independent radiology review in 10 patients with RMC. RMC is a very rare malignancy. And out of these 10 patients, nine had disease control as best response. So we were able to control this disease in nine out of 10 patients. And two out of 10 actually have formal partial responses by resist criteria. And this led to a PFS, a progression-free survival, that was about 3.5 months. And it may sound short, but for a disease that has an overall survival of 13 months and for patients that essentially have no other option, increasing the progression free survival by 3.5 months is a big deal.

And indeed, when we looked at the overall survival outcomes of these patients it was even higher after administering bevacizumab erlotinib, it is about seven months. So, seven months extra overall survival. And when we analyze, interestingly enough, the overall survival from diagnosis of these patients that received this regimen, the median overall survival from diagnosis had increased from 13 months, that was based on our prior data without that regimen, now to about 20 months. Almost all of these patients do develop resistance eventually. And so we need to determine how resistance develops and how we can target these pathways better. However, I think that this is a good start for a disease that has a tremendous unmet need for new therapies.