VICC’s clinical trials chief weighs the merits of IO/IO and IO/TKI regimens.

Debate continues as to whether dual immunotherapy (IO/IO) or immunotherapy in combination with a VEGF tyrosine kinase inhibitor (IO/TKI) is best suited to treat renal cell carcinoma (RCC).

“This is basically ‘the topic’ now in kidney cancer. You can’t attend a meeting, I can’t give a talk without discussing the IO/IO versus IO/TKI dilemma,” said Brian Rini, M.D., chief of clinical trials at Vanderbilt-Ingram Cancer Center, in an OncLive® feature. “There are arguments to be made for both.”

A Case for Immunotherapy

First-line dual immunotherapy commonly includes ipilimumab and nivolumab in combination. The “ipi-nivo” regimen earned FDA approval several years ago after phase 3 trial data showed it improved survival in patients with advanced RCC, as compared to sunitinib.

Both ipilimumab and nivolumab are antibodies, targeting CTLA-4 and PD-1, respectively. When administered alone, even low doses of nivolumab provide antitumor activity in metastatic disease. Its benefits have been demonstrated in both non-clear cell and clear cell RCC.

With longitudinal data in hand, dual immunotherapy “has a more mature dataset and durability as its hallmark,” Rini said.

A Role for TKIs

Many FDA-approved TKIs offer a mechanistic alternative for first-line RCC therapy. These drugs target the VEGF pathway to limit angiogenic cytokine release. They include small molecule inhibitors as well as monoclonal antibodies.

TKIs are costly and associated with some toxicities, though their added benefit is tough to ignore. “Going for the IO/TKIs [yields] higher response rates, more tumor shrinkage, more upfront disease control,” Rini said. “Whether these benefits will remain durable remains to be seen.”

More Options for Success

Rini said he could argue for either therapeutic approach and is glad to have options. “As a provider and as a patient advocate, I think we want more and more active regimens.” He recently participated in a podcast debating the merits of first-line RCC therapies.

Not surprisingly, he notes the decision must come down to the individual case. A patient’s age, overall health, sites and burden of metastatic disease and comorbidities necessitate personalized treatment regimens. Rini encourages providers to carefully evaluate study populations before translating trial results to their own clinic.

“It’s great to have multiple active regimens in a disease because patients are going to respond differently, they’re going to tolerate differently, even among different TKI partners,” he said.


Brian Rini, M.D.

Brian Rini, M.D., is Ingram Professor of Medicine and chief of clinical trials at Vanderbilt-Ingram Cancer Center. He is an internationally recognized leader in genitourinary oncology, kidney cancer and clinical drug development.