Bradley A. McGregor, MD, discusses current and future second-line therapy options following frontline tyrosine kinase inhibitor and immunotherapy for patients with advanced renal cell carcinoma.
Bradley A. McGregor, MD, clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School, discusses current and future second-line therapy options following frontline tyrosine kinase inhibitor (TKIs) and immunotherapy (IO) for patients with advanced renal cell carcinoma (RCC).
The choice of second-line therapy is based on limited data since frontline IO/TKI combinations are relatively new. McGregor says cabozantinib (Cabometyx) is a strong single-agent option based on how it performed as a comparator arm in the CANTATA trial (NCT03428217). Lenvatinib (Lenvima) and everolimus (Afinitor) are also a second-line option.
More trials are ongoing to research the optimal treatment following IO/TKI frontline therapy. McGregor says there were impressive results for lenvatinib plus pembrolizumab (Keytruda) in patients who had received prior IO. The currently-enrolling CONTACT-03 trial (NCT04338269) is investigating cabozantinib plus atezolizumab (Tecentriq) versus cabozantinib alone. Another trial accruing patients is the TiNivo-2 trial (NCT04987203) of tivozanib (Fotivda) plus nivolumab (Opdivo) versus tivozanib in the second line.
A phase 3 trial (NCT04586231) of belzutifan (Welireg) plus lenvatinib versus cabozantinib is ongoing, as well as a phase 3 trial (NCT04195750) of belzutifan versus everolimus.
These trials will show whether additional immunotherapy is effective in patients who are refractory or relapsed following frontline IO/TKI.
0:08 | If a patient does not receive cabozantinib in the frontline setting, I think given immediate results and what we saw in the CANTATA tracking, cabozantinib is a very appropriate option as well as lenvatinib and everolimus given the phase 2…improvement in survival versus everolimus, so I think either one of those would be a reasonable option. Obviously, if they received cabozantinib frontline, I'm going to use lenvatinib/everolimus, and if they received lenvatinib/pembrolizumab in the frontline, I'm going look at cabozantinib. I think we certainly need to do better and there are multiple trials ongoing in this frontline.
0:43 | One of the questions we don't really know the answer is if you progress on IO, is there a role for continuing IO? We've seen some pretty impressive results for the combination of lenvatinib and pembrolizumab for patients who progress on prior immunotherapy: response rates over 50%. Is that from lenvatinib or is that truly from the combination? There are multiple trials ongoing: the [CONTACT-03] trial looking in cabozantinib and atezolizumab versus cabozantinib that has completed accrual. Right now, the TiNivo-2 trial looking at tivozanib versus tivozanib and nivolumab for patients who have progressed on immunotherapy even at frontline or second-line setting is currently accruing. There are other trials looking at adding belzutifan to lenvatinib versus cabozantinib. And then we look forward the results of the phase 2 trial of belzutifan versus everolimus in the treatment refractory setting.