Effect of Anti-Angiogenesis/Immunotherapy Combo in Poor-Risk RCC

June 10, 2019
Jim Kling

Findings from a planned subanalysis of IMmotion151 looked at combination atezolizumab and bevacizumab in patients with RCC and sarcomatoid histology.

In patients with renal cell carcinoma (RCC) and sarcomatoid histology, the combination of atezolizumab and bevacizumab demonstrated better progression-free survival (PFS) and overall response rate (ORR) compared with sunitinib. The findings (abstract 4512) come from a planned subanalysis of the IMmotion151 clinical trial and were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

“In some ways, this reinforces the overall story that if you take anti-angiogenesis therapy combined with immunotherapy, you get better results, and this seemed to be robustly true in a poor-risk population,” Timothy Gilligan, MD, associate professor of medicine and vice chair for education at the Cleveland Clinic Taussig Cancer Institute, told Cancer Network. “The biological markers they looked at were consistent with this hypothesis, so it kind of made sense.”

A total of 10% to 20% of advanced RCC patients have sarcomatoid histology and don’t respond well to vascular endothelial growth factor (VEGF) inhibitors. The researchers analyzed data from 142 patients with sarcomatoid histology participating in the IMmotion151 trial, which randomized 915 participants to atezolizumab plus bevacizumab every 3 weeks or daily oral sunitinib. The full study results, published earlier this year in The Lancet, showed an overall increase in progression-free survival (PFS) in the atezolizumab plus bevacizumab group.

The median PFS in the atezolizumab plus bevacizumab group was 8.3 months vs 5.3 months in the sunitinib group (hazard ratio [HR], 0.52; 95% CI, 0.34–0.79). In the intention-to-treat (ITT) population, median PFS for these groups was 11.2 and 8.4 months, respectively (HR, 0.83; 95% CI, 0.70–0.97). In programmed death ligand 1 (PD-L1)–positive sarcomatoid patients, the median PFS was 8.6 months vs 5.6 months (HR, 0.45; 95% CI, 0.26–0.77), and in PD-L1–negative sarcomatoid patients, they were 11.2 and 7.7 months, respectively (HR, 0.74; 95% CI, 0.57–0.96), in the atezolizumab plus bevacizumab vs sunitinib groups.

ORR also favored the atezolizumab plus bevacizumab group: it was 49% (95% CI, 36%–61%) in these patients compared with 14% in the sunitinib group (95% CI, 7%–23%) overall. However, the difference was not significant in the ITT population (37% vs 33%). ORR was better in the atezolizumab plus bevacizumab group among PD-L1–positive subjects with sarcomatoid histology (56% ORR; 95% CI, 38%–72% vs 12% ORR; 95% CI, 5%–24%]), but not in PD-L1–negative patients (43% vs 35%).

Median overall survival favored the atezolizumab plus bevacizumab group vs the sunitinib group (21.7 months vs 15.4 months), but did not reach statistical significance (HR, 0.64; 95% CI, 0.41–1.01), and there was no statistically significant difference in any of the subcategories. Among patients with more than a 20% sarcomatoid component, ORR was 44% in the atezolizumab plus bevacizumab group vs 4% in the sunitinib group, with corresponding complete response rates of 7% and 0%, respectively.

Biomarker analysis showed that higher PD-L1 expression was more common in tumors with sarcomatoid histology than in those with non-sarcomatoid histology (63% vs 39%); in addition, in patients with sarcomatoid histology vs those with non-sarcomatoid histology, the prevalence of high angiogenesis gene expression signature subset was lower in (34% vs 65%), and the prevalence of high T-effector gene expression signature subset was higher (54% vs 40%), all of which were statistically significant.

The safety signals were similar to those seen in the original study.