Current and Potential Second-Line Therapies Following IO/TKI in RCC

EP: 1.Key Considerations for Selecting Frontline Therapy in Advanced RCC

EP: 2.Recommendations for Treating Non–Clear Cell RCC

EP: 3.Ongoing Trials Investigate Intensified Frontline Therapy for RCC

EP: 4.Long-Term Cabozantinib/Nivolumab Data Show Improved Survival in RCC

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EP: 5.Current and Potential Second-Line Therapies Following IO/TKI in RCC

EP: 6.Factors Influencing Frontline Therapy Options for Favorable-Risk RCC

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.

TRANSCRIPTION:

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.