EIKCS 2022: Debate: In Favor of IO/IO

(UroToday.com) In the fifth session of the 2022 International Kidney Cancer Symposium (IKCS): Europe meeting focusing on first-line systemic therapy in advanced kidney cancer, Dr. Aristotelis Bamias presented the second side of the debate regarding treatment selection, defending the approach of dual immune checkpoint inhibition with nivolumab and ipilimumab.

He first began by emphasizing that the most important outcomes when considering treatment selection are long-term remission, median overall survival, and potentially even cure. He suggested that palliative control, response rates, quality of life, and median progression-free survival are less important.

Dr. Bamias highlighted that, as per all international guidelines, we need to begin our approach to treating patients with metastatic renal cell carcinoma on the basis of risk stratification based on the IMDC criteria.

He then began by focussing on patients with intermediate and poor risk disease in which there are four current standards of care including ipilimumab/nivolumab (CheckMate-214), axitinib/pembrolizumab (KEYNOTE-426), cabozantinib/nivolumab (CheckMate-9ER), and lenvatinib/pembrolizumab (CLEAR). He emphasized that only two of these (CheckMate-214 and KEYNOTE-426) included overall survival as a primary endpoint.


Dr. Bamias then suggested that while there was a relatively long follow-up for both CheckMate-214 (median 55 months) and KEYNOTE-426 (median 42.8 months), the follow-up for the last two are “inadequate” (23.5 and 26.6 months, respectively).

Dr. Bamias then emphasized that long-term remission “may be prelude of cure”. He suggests that, as of today, there is only one approach with evidence of durable remission, nivolumab, and ipilimumab. For those patients, he suggested that those patients who have no progression after 2 years, most will subsequently “never” progress.


In contrast to these long-term data from CheckMate-214, Dr. Bamias said that he “can’t see a plateau” in the progression-free survival curve from KEYNOTE-426


Moving from the intermediate and poor risk subgroup to discuss treatment approaches for patients with favourable risk, he emphasized that, based on data from CheckMate-214, a combined IO/IO approach is not “proper treatment”. However, he first suggested that “a sizeable proportion” of these patients do not need systemic therapy based on data from Dr. Rini which demonstrated the feasibility of observation for these patients. Based on this study, nearly half of patients were able to continue with observation, even after progression.

Dr. Bamias then highlighted data from KEYNOTE-426, CheckMate-9ER, and CLEAR showing no significant benefit to the combined IO and TKI approach compared to sunitinib monotherapy in this patient group.

In conclusion, Dr. Bamias suggested (based on data available today) that the “only proven chance of cure” for patients with intermediate and poor risk disease comes from the combination of nivolumab and ipilimumab. Further, many patients with favourable risk disease do not require systemic therapy at the time of diagnosis and, for those who do, tyrosine kinase monotherapy may be the “best choice for patients, doctors, and health systems”. Thus, he concluded that IO/TKI combinations do not seem to be the best choice for any patients with metastatic renal cell carcinoma.

Presented by: Aristotelis Bamias, MD, PhD, Αssociate Professor, University of Athens, Greece