During a Case-Based Roundtable® event, Shilpa Gupta, MD, led a discussion on the combination of immunotherapy and tyrosine kinase inhibitors for patients with advanced renal cell carcinoma in the second article of a 2-part series.
DISCUSSION QUESTIONS
SHILPA GUPTA, MD: Between the available immunotherapy and TKI [tyrosine kinase inhibitor] combinations [for patients with mRCC], which is your preferred therapy?
PALLAVI JASTI, MD: Initially, I used axitinib [Inlyta] plus pembrolizumab [Keytruda] a lot because it was the first one on the market,1 but more recently, most of my patients are getting cabozantinib [Cabometyx] plus nivolumab [Opdivo].
BAIDEHI MAITI, MD: I wanted to add, if somebody has an active autoimmune disorder, I would factor that in [when choosing treatment] as well, and I wouldn't consider ipilimumab [Yervoy] plus nivolumab in that setting.
GUPTA: [In that case], would you only use a TKI and avoid immunotherapy altogether?
MAITI: It depends on how intense [the patient's autoimmune disorder] is and if I can work with...whoever is addressing that. So, I might use a TKI and pembrolizumab or the cabozantinib/nivolumab combination, but if there is an active autoimmune disorder, I'll probably avoid those altogether.
DISCUSSION QUESTIONS
ANEEL CHOWDHARY, MD: There's a significant survival benefit [with these combinations], especially in intermediate- and poor-risk patients, but the reason we're losing that benefit is because of the immunotherapy, in my opinion. If you look at ipilimumab/nivolumab, the benefit in survival vs TKI is maintained...because [the patient is] on immunotherapy to begin with.2 I think that is the benefit that's carrying over. Patients on sunitinib [Sutent], for example, are getting on immunotherapy later and that survival benefit may be lost. But progression-free survival and the median duration of response are important parameters here, [and show] that these regimens are still very effective; it’s just that when you cross over to immunotherapy later...the [regimens] are losing some of the survival edge.
GUPTA: If you recall from the [CheckMate 9ER study (NCT03141177)], around 10% of patients discontinued cabozantinib due to adverse events [AEs] and discontinuation due to [AEs associated with] nivolumab was also around 10% to 11%.3 With lenvatinib [Lenvima], the discontinuation rate was 25.6%, and...we also see that patients who start at the 20-mg mandated dose [of lenvatinib]…28% are stopping pembrolizumab and 13% are stopping both,4 as opposed to less than 10% on [for those patients on] cabozantinib/nivolumab.3 So I think this is everybody's clinical experience too, and I don't think anybody in the group said they don't see these challenges with lenvatinib/pembrolizumab.
ALEXANDER BARSOUK, MD: For me, I will probably use more cabozantinib upfront. I've been using it [early and have had] a good experience. [I haven't] had much concern when...using cabozantinib in the second-line setting because there are strong data [for it and it's] associated with a good quality of life. In my personal experience, it's a good combination and user friendly, but sometimes you have to dose reduce the cabozantinib.
GUPTA: So you're saying early on that you would use only cabozantinib, but you are now a more open to using a doublet because of [these data]? Is that fair to say?
BARSOUK: Yes, before I would use a different doublet...[but earlier ones were] kind of toxic. Now I would use more cabozantinib/nivolumab and not worry about what to use in the second-line setting, because there are so many options available nowadays.
MAITI: I took up axitinib/pembrolizumab initially and got very comfortable with it, but now with the current data I have switched to cabozantinib/nivolumab.... For [patients with] symptomatic high disease burden, especially if they have liver metastases, I probably lean towards lenvatinib/pembrolizumab, but that will probably be the only situation. Otherwise, I would pick cabozantinib/nivolumab.
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