Ulka Vaishampayan, MD: What about the evolution of the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria—from initially being prognostic to now being used as predictive when selecting treatment? What do you think, Tian? How should we use the criteria?

Tian Zhang, MD: We’ve been talking about the IMDC criteria quite a bit. As a reminder for our audience, this is really a set of clinical criteria from less than a year from initial diagnosis to treatment. The Karnofsky Performance Status as well as a list of laboratory findings of hypercalcaemia, neutrophilia, thrombocytosis, as well as anemia really reflect the inflammatory and paraneoplastic types of syndromes that patients present with.

Over a decade ago, Daniel Heng and his colleagues at the Dana-Farber Cancer Institute and the International Metastatic Renal Cell Carcinoma Database Consortium gathered the data. Through multivariate analyses, these 6 risk factors came out to be prognostic. The initial data that were published in the Journal of Clinical Oncology in 2009 showed that patients who had 0 risk factors actually had a really good prognostic outcome—about a 4-year overall survival. Patients with 1 or 2 risk factors with intermediate-risk disease had about a 2-year overall survival. For patients with poor-risk disease with 3 or more risk factors, that median overall survival was quite poor—at only about 9 months.

We’ve come a long way from using that as a prognostic risk stratification to now stratification in our phase III frontline trials. Because of that, and because the patients really have fallen into these categories of favorable, intermediate, and poor-risk disease, we now have novel immune therapy combinations that have differing efficacies and data comparatively with the standard-of-care VEGF inhibitors.

In that setting, IMDC criteria really have changed and moved into being more of a predictive biomarker, in terms of the clinical factors we can choose from to think about treatment selection. Because of that, I think you saw the NCCN [National Comprehensive Cancer Network] Guidelines change about a year ago to reflect the growing categories and dependence on IMDC criteria. In real-world practice, we certainly use and turn to the IMDC criteria first to think about what the right treatment options are for our patients.

Ulka Vaishampayan, MD: Wonderful. What are people’s thoughts on mechanism of action and the targets for available VEGF-TKIs [tyrosine kinase inhibitors]? Matt, what do you think?

Matthew T. Campbell, MD, MS: Starting in 2016 with the publication of the METEOR study, and then with the 3-arm study of lenvatinib and everolimus versus everolimus or lenvatinib alone, we started to see agents that had novel targets that were different from many of the earlier drugs that had come out, such as pazopanib, sunitinib, axitinib, sorafenib. By targeting VEGFR2 but also by hitting MET and AXL as well as other pathways, cabozantinib seems to be, in my opinion, the most active TKI that we have in terms of how it’s demonstrated overall survival advantage post TKI. It’s a drug I have a lot of faith in, and even for use in later-line settings.

Lenvatinib is a very interesting drug. It targets the FGFR axis, and we’re seeing the drug come along quickly in a variety of different tumor types. Lenvatinib was just approved with pembrolizumab in uterine cancer. It’s showing a lot of strength across a number of different fronts. It clearly is doing something. It is targeting the cancer cell as well as the microenvironment in unique ways that may make it a great partner with immunotherapy. I can say the same about cabozantinib.

Transcript Edited for Clarity