First-line Immuno-Oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International Metastatic Renal-cell Carcinoma Database Consortium

Dudani S, Graham J, Wells JC, et al.
European Urology, Volume 0, Issue 0, Article in Press
DOI: https://doi.org/10.1016/j.eururo.2019.07.048

Abstract

Background

In metastatic renal-cell carcinoma (mRCC), recent data have shown efficacy of first-line ipilimumab and nivolumab (ipi-nivo) as well as immuno-oncology (IO)/vascular endothelial growth factor (VEGF) inhibitor combinations. Comparative data between these strategies are limited.

Objective

To compare the efficacy of ipi-nivo versus IO-VEGF (IOVE) combinations in mRCC, and describe practice patterns and effectiveness of second-line therapies.

Design, setting, and participants

Using the International Metastatic Renal-cell Carcinoma Database Consortium (IMDC) dataset, patients treated with any first-line IOVE combination were compared with those treated with ipi-nivo.

Intervention

All patients received first-line IO combination therapies.

Outcome measurements and statistical analysis

First- and second-line response rates, time to treatment failure (TTF), time to next treatment (TNT), and overall survival (OS) were analysed. Hazard ratios were adjusted for IMDC risk factors.

Results and limitations

In total, 113 patients received IOVE combinations and 75 received ipi-nivo. For IOVE combinations versus ipi-nivo, first-line response rates were 33% versus 40% (between-group difference 7%, 95% confidence interval [CI] –8% to 22%, p =  0.4), TTF was 14.3 versus 10.2 mo (p =  0.2), TNT was 19.7 versus 17.9 mo (p =  0.4), and median OS was immature but not statistically different (p = 0.17). Adjusted hazard ratios for TTF, TNT, and OS were 0.71 (95% CI 0.46–1.12, p =  0.14), 0.65 (95% CI 0.38–1.11, p =  0.11), and 1.74 (95% CI 0.82–3.68, p =  0.14), respectively. Sixty-four (34%) patients received second-line treatment. In patients receiving subsequent VEGF-based therapy, second-line response rates were lower in the IOVE cohort than in the ipi-nivo cohort (15% vs 45%; between-group difference 30%, 95% CI 3–57%, p =  0.04; n = 40), though second-line TTF was not significantly different (3.7 vs 5.4 mo; p =  0.4; n = 55). Limitations include the study’s retrospective design and sample size.

Conclusions

There were no significant differences in first-line outcomes between IOVE combinations and ipi-nivo. Most patients received VEGF-based therapy in the second line. In this group, second-line response rate was greater in patients who received ipi-nivo initially.

Patient summary

There were no significant differences in key first-line outcomes for patients with metastatic renal-cell carcinoma receiving immuno-oncology/vascular endothelial growth factor inhibitor combinations versus ipilimumab and nivolumab.

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