medwireNews: Phase II trial results suggest that atezolizumab plus bevacizumab may offer an effective treatment for unresectable locally recurrent or metastatic renal cell carcinoma (RCC) patients with variant histology or with at least 20% sarcomatoid differentiation.
The study recruited 60 patients who had not previously received PD-L1/PD-1 inhibition or bevacizumab, the majority of whom had IMDC intermediate-risk disease (55%) and had not received prior treatment (65%).
This included 18 clear cell RCC patients with at least 20% sarcomatoid differentiation, as well as smaller groups with variant papillary (n=12), chromophobe (n=10), unclassified RCC (n=9), TFE3 translocation (n=5), collecting duct (n=5), and medullary (n=1) histology with or without sarcomatoid differentiation.
The patients received a median 9.5 cycles of atezolizumab 1200 mg and bevacizumab 15 mg/kg every 3 weeks, with 15 patients continuing treatment at time of analysis, the researchers write in the Journal of Clinical Oncology.
After a median of 13 months, the primary endpoint of objective response rate (ORR) was 33%, including 26% of patients with variant histology without sarcomatoid differentiation, 38% of those with variant histology and sarcomatoid differentiation, and 50% of those with clear cell RCC and sarcomatoid differentiation.
Among the variant histology subgroup, the ORR ranged from 10% of chromophobe to 40% of collecting duct patients, as well as an OR in the only medullary histology case, but analysis failed to detect a significant correlation between type of histology and response.
Median time to response was 2.7 months, and it lasted a median of 8.9 months. Median progression-free survival was 8.3 months and median overall survival was not reached by time of analysis, the researchers add.
PD-L1 analysis of 36 patients with sufficient tissue suggested no differences in response for those with clear cell RCC with sarcomatoid differentiation according to PD-L1 status, with ORRs in positive and negative patients of 50% and 29%. However, variant histology RCC patients who were PD-L1-positive had a significantly higher ORR than their negative counterparts, at 67% versus 14%.
“[O]ur results suggest that PD-L1 is intriguing as a biomarker for response to atezolizumab and bevacizumab in variant histology RCC”, say Toni Choueiri, from Dana Farber Cancer Institute in Boston, Massachusetts, USA, and co-investigators, who now plan further investigation for markers of response and resistance.
The researchers describe the combination treatment as “generally well tolerated” with the most common being fatigue (35%), proteinuria (35%) and musculoskeletal pain (33%). Around a fifth of patients experienced diarrhoea, rash, hypertension and pruritis. In all, 33% of patients had at least one grade 3 event; there were no grade 4 or 5 events but 10% of patients required high-dose corticosteroids for immune-related events.
“Although a larger confirmatory randomized study would be needed to evaluate the treatment effect of the combination of atezolizumab and bevacizumab, the current study provides support for the use of immunotherapy/VEGF combinations in the management of variant histology RCC and RCC with sarcomatoid differentiation”, the team concludes.
McGregor BA, McKay RR, Braun DA, et al. Results of a multicenter phase II study of atezolizumab and bevacizumab for patients with metastatic renal cell carcinoma with variant histology and/or sarcomatoid features. J Clin Oncol; Advance online publication 13 November 2019. DOI: 10.1200/JCO.19.01882
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