Physician Views: Immunotherapies set to redefine the first-line treatment of renal cell carcinoma

Since it was approved in the US in April, Bristol-Myers Squibb's combination of Opdivo and low-dose Yervoy has enjoyed strong uptake in previously untreated intermediate and poor-risk renal cell carcinoma (RCC) patients, capturing between 30 percent and 35 percent of the first-line market. In the CheckMate-214 study, the combination of Opdivo and low-dose Yervoy was shown to reduce the risk of death by 37 percent versus Pfizer's Sutent.

Competition is set to emerge in the form of another immunotherapy-based regimen, which combines Pfizer and Merck KGaA's Bavencio with Pfizer's tyrosine kinase inhibitor Inlyta. Data recently presented at the ESMO congress shows that versus Sutent, the combination reduced the risk of disease progression or death by 39 percent in PD-L1 positive patients and 31 percent in patients irrespective of PD-L1 status.

The Bavencio/Inlyta combination is yet to demonstrate a significant overall survival benefit (as data are not mature enough), but it has also been shown to work in favourable risk patients and Inlyta is a frequently used treatment for RCC. Furthermore, though Opdivo/low-dose Yervoy has been granted an all-comers label in the US, CheckMate-214 was not sufficiently powered to show efficacy by PD-L1 status groups. Post hoc analyses do indicate, however, that the combination is more effective in PD-L1 positive patients - see ESMO 2018 analysis - Bavencio makes its biggest splash yet, with Keytruda waiting in the wings.

To get a better understanding of how the intricacies of these two datasets may impact physician attitudes towards the treatment of first-line RCC patients, we are snap-polling US oncologists…


Q. Do you consider the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) to be a standard-of-care first-line therapy for intermediate- and poor-risk RCC patients?


Yes - but only in PD-L1 expressers



Q. Data from the JAVELIN Renal 101 study showed the combination of Bavencio (avelumab) and Inlyta (axitinib) significantly improved progression-free survival (PFS) in previously untreated RCC patients versus Sutent (sunitinib) regardless of risk group; i.e. it also worked in favourable-risk patients.

In PD-L1 positive patients, the combination demonstrated median PFS of 13.8 months versus 7.2 months for Sutent, reducing the risk of disease progression or death by 39 percent. In patients irrespective of PD-L1 status, the combination demonstrated median PFS of 13.8 months versus 8.4 months for Sutent, reducing the risk of disease progression or death by 31 percent.

Are these data practice changing?


Yes - if the combination subsequently demonstrates an overall survival benefit



Q. If approved on the basis of the JAVELIN Renal 101 data, would you expect to use the combination of Bavencio and Inlyta in favour of the Opdivo/Yervoy combination in previously untreated RCC patients?







Q. It has also been announced that the combination of Keytruda (pembrolizumab) and Inlyta has demonstrated both significant PFS and overall survival benefits versus Sutent in previously untreated RCC regardless of patient risk-status and PD-L1 expression status.

Let's assume that both the Bavencio/Inlyta and Keytruda/Inlyta combinations end up with very similar data readouts and clinical profiles; access and price can also be assumed to be similar. Would you favour one pairing over the other?

Yes - Bavencio/Inlyta

Yes - Keytruda/Inlyta



Q. Cabometyx (cabozantinib) is also approved as a first-line treatment for RCC, but key opinion leader feedback suggests its use in this setting will be significantly limited by the adoption of immunotherapies.

With this in mind, however, do you think the status of Cabometyx as a leading standard-of-care therapy in second-line RCC patients will be enhanced as an alternative mechanism once disease progression has occurred following immunotherapy?


Yes - slightly

Yes - moderately

Yes - significantly

Results and related analysis will shortly be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here

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