From the Journals

No difference between ipilimumab/nivolumab combo and immunotherapy plus VEGF for metastatic RCC



There is no significant difference in response or survival rates between the combination of ipilimumab/nivolumab (ipi-nivo) and immuno-oncology plus vascular endothelial growth factor inhibition (IOVE) for patients with metastatic renal cell carcinoma.

Therefore, the treatment should probably be directed by patient preferences, among other things, Shaan Dudani, MD, and colleagues wrote in European Oncology.

“Given the current lack of evidence to suggest a difference in efficacy between treatment strategies, patients, clinicians and policy makers are likely to take into account other considerations, such as toxicity, cost, logistics, prognostic categories, and patient preferences in deciding between the various front-line [immuno-oncology] combination regimens,” wrote Dr. Dudani, of the University of Calgary, and coauthors.

The team examined response rates among 263 patients with metastatic renal cell carcinoma from the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) dataset. Patients treated with any first-line IOVE combination (n = 113) were compared with those treated with ipi-nivo (n = 75). Patients were about 62 years old. The most common sites of metastasis were liver (about 20%) and bone (about 33%), and about 20% had sarcomatoid features (about 20%). Most (about 75%) had multiple metastatic sites.

Thirty percent of those in the IOVE group and 40% in the ipi-nivo group had received second-line treatments. These included axitinib, levantinib plus severolimus, nivolumab alone, pazopanib, and sunitinib, as well as other treatments.

At a mean follow-up of 11.7 months, the response rates were 33% for IOVE and 40% for ipi-nivo. This difference was not statistically significant (between group difference, 7%; 95% confidence interval, –8% to 22%; P = .4). Complete response occurred in 2% in IOVE and 5% of the ipi-nivo group.

The time to treatment failure was 14.3 months for IOVE and 10.2 months for ipi-nivo – again not a significant difference (P = .2). Time to next treatment also was not significantly different (19.7 vs. 17.9 months; P = .4). Neither group met the study’s overall survival goal.

After adjustment for IMDC risk score, hazard ratios for death were 0.71 for IOVE and 1.74 for ipi-nivo. There were no significant between-group differences when comparing intermediate- and poor-risk patients or when the analysis was restricted only to favorable-risk patients. Among 55 who received second-line therapy, there was also no significant difference in time to treatment failure.

“It was interesting, though not surprising, to observe that the majority [88%] of second-line therapies in this cohort were VEGF-based following ipi-nivo vs. IOVE combinations,” the authors noted. “The higher response rates observed in patients receiving second-line VEGF combinations is noteworthy and thought provoking. Biologically, it is plausible that VEGF-based second-line therapy would be more likely to be effective in the VEGF-naive ipi-nivo cohort. It remains to be seen whether the numerical difference in time to treatment failure becomes significant with increased sample size and further follow-up, and whether this contributes to differences in overall survival, which ultimately impacts treatment selections in the first-line setting.”

Dr. Dudani had no financial disclosures.

SOURCE: Dudani S et al. Euro Onc. 2019 Aug 22. doi: 10.1016/j.eururo.2019.07.048.

Next Article: