RCC Experts Consider Immunotherapy Integral to Optimizing Adjuvant Care

Michael Atkins, MD

Looking ahead to 2020, most participants on an expert panel projected that immunotherapy will be critical to optimizing outcomes in the adjuvant setting for patients with renal cell carcinoma (RCC).

The panel, which convened at the 2016 International Kidney Cancer Symposium after a 6-presentation session on the future of adjuvant therapy, was moderated by Michael Atkins, MD, deputy director and professor at the Georgetown University Lombardi Comprehensive Cancer Center.

Atkins presented the panelists with 5 options of what will become the optimal choice for adjuvant RCC care over the next 5 years: 1) VEGFR TKI followed by anti­—PD-1-based therapy; 2) ipilimumab (Yervoy)/nivolumab (Opdivo) followed by VEGFR TKI and then followed by “other”; 3) VEGF + PD-1 inhibition followed by “other”; 4) Other; and 5) No idea.

Most panelists selected an option that included checkpoint inhibition upfront. Charles Drake, MD, PhD, codirector, Prostate Cancer Multidisciplinary Clinic, professor of Oncology, Johns Hopkins Medicine, commented that VEGF plus PD-1 inhibition followed by “other” may be an optimal choice because of the potential for combinatorial effects. He added that the VEGF/PD-1 treatment is less toxic than the ipilimumab/nivolumab combination and achieves comparable results, while also noting that, since all the data are not yet available, it is impossible to know which approach will be optimal.

David McDermott, MD, associate professor of Medicine at Harvard Medical School and director of the Biologic Therapy Program at Beth Israel Deaconess Medical Center, cited experience in melanoma with patients who have deep and durable responses to ipilimumab as a reason for selecting the ipilimumab/nivolumab regimen. Hans Hammers, MD, PhD, an assistant professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins Medicine, concurred with McDermott, citing positive results with the combination in RCC from the CheckMate-016 trial.

Guru Sonpavde, MD, associate professor of Medicine, director of Urologic Malignancies, UAB School of medicine, also selected dual checkpoint blockade, but warned against a “one-size-fits-all” approach. “I like the idea of ipilimumab plus nivolumab in patients with good performance status, but I think there will be a big subset of patients in the community that will not qualify for the combination. I really think there will be a two-tiered approach—maybe [going] with sequential single-agent therapy [in patients with a higher ECOG performance status].”

Neeraj Agarwal, MD, associate professor in the Division of Oncology, Department of Medicine, director of the Genitourinary Medical Oncology Program, Huntsman Cancer Institute at the University of Utah, opted for VEGF plus PD-1 inhibition, noting that there is no way to know if patients will have a durable response on the ipilimumab/nivolumab regimen, and treatment with VEGF + PD-1 inhibition provides patients with the opportunity to have an immediate and durable response.

Following the panel discussion, the floor was opened for questions from the audience. Expanding on earlier discussion, an audience member asked if, in the absence of toxicity and progression, patients have a deep response to a drug like ipilimumab or nivolumab, what the duration of therapy should be before consideration is given to taking patients off the drug.

In response, McDermott pointed out that there are not many data to guide practice. The phase I studies of nivolumab in RCC only had about 30 patients at the 2-year point when the drug was stopped. In contrast, the melanoma cohort at 2 years had closer to 100 patients. When these patients stopped at 2 years, some of them progressed, and only a subset was responsive to nivolumab when it was reintroduced.

Compared to melanoma studies, the kidney cancer response rate is lower, as is the number of patients who continue to respond off drug. For this reason, there will be a group of patients who come off therapy, progress, and are then unable to respond to salvage treatment.

Another audience member voiced disappointment that the panelists were not convinced that by 2020, physicians would be able to select appropriate treatment based on the patient profiles. Panelists countered that they do believe that they will be able to identify patients most likely to benefit from single-agent PD-1 therapy or VEGF TKIs. Even if combination therapies become first-line therapies, if there is a predictive marker, panelists indicated they would use single-agent PD-1.

“With better technologies and newer samples, I think we can come up with signatures for treatments,” commented McDermott.

Overall, panelists agreed upon the importance of investigating prognostic markers in order to prevent overtreatment or incorrect treatment of RCC and expressed enthusiasm for the forthcoming data on combination therapy selection and sequencing.

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The final panelist, Tian Zhang, MD, a medical oncologist and a medical instructor at the Duke University School of Medicine, said that though she would like to select “other” for vaccine therapy, she thinks that the optimal treatment is likely patient specific: some patients will “certainly have longer responses on VEGF inhibitors, but it will really depend on the patients and their own criteria,” in deciding which treatment is best for them. On a population level, however, she selected the ipilimumab/nivolumab regimen for the duration in response.