The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to the results of subgroup analyses of patients with advanced clear cell renal cell carcinoma (RCC) enrolled in a phase 3 clinical trial evaluating the combination of the programmed cell death-1 (PD-1) inhibitor, pembrolizumab, plus axitinib, a selective vascular epithelial growth factor receptor (VEGF)-1,-2, and -3 receptor tyrosine kinase inhibitor, versus single-agent sunitinib, the efficacy benefits of the former regimen previously observed for the overall study population were also seen in the subgroup of patients with intermediate- or poor-risk disease. The findings of this study were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

In the open-label, phase 3 KEYNOTE-426 trial ( Identifier: NCT02853331), the primary end points of progression-free survival (PFS) and overall survival (OS) were significantly longer, and the secondary end point of overall response rate (ORR) was significantly higher, for the overall population of patients with advanced clear cell carcinoma randomly assigned (1:1) to receive pembrolizumab plus axitinib (200 mg IV every 3 weeks plus axitinib 5 mg orally twice daily) compared with those in the sunitinib arm (50 mg orally once daily for 4 weeks every 6 weeks).

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Furthermore, these results, in conjunction with the corresponding safety data showing manageable toxicity for the combination of pembrolizumab plus axitininib, led to its recent approval by the US Food and Drug Administration (FDA) for the treatment of patients with advanced RCC in the first-line setting.3

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This analysis of data from the KEYNOTE-426 study focused on determining outcomes in specific subgroups of patients with favorable or intermediate- or high-risk features as assessed by the International Metastatic RCC Database Consortium (IMDC) risk groups, as well as in those with disease specifically characterized by sarcomatoid features. Another study objective was to determine the thresholds of percentage of tumor shrinkage from baseline in these subgroups. 

In the overall study population with measurable disease, 94% versus 85% of patients treated with immunotherapy-based treatment compared with sunitinib had some decrease in the size of target lesions. The respective rates for those with tumor shrinkage by 60% or higher (42% versus 16%), 80% or higher (17% versus 6%), and 100% (ie, complete response [CR]; 9% versus 3%) favored patients receiving pembrolizumab plus axitinib.  

In the subgroup of patients with IMDC favorable-risk disease (269 individuals), rates of 1-year OS (95% vs 94%; hazard ratio [HR], 0.64; 95% CI, 0.24-1.68), 1-year PFS (68% vs 60%; HR, 0.81; 95% CI, 0.53-1.24), and overall response (OR; 66.7% vs 49.6%) favored patients in the immunotherapy-based arm. However, these differences were more pronounced in the 592 patients with IMDC intermediate- or poor-risk disease, with respective rates of 1-year OS (87% vs 71%; HR, 0.52; 95% CI, 0.37-0.74), 1-year PFS (56% vs 40%; HR, 0.67; 95% CI, 0.53-0.85) and OR (55.8% vs 29.5%) for those receiving pembrolizumab/axitinib versus sunitinib.

Regarding the subgroup of patients with disease characterized by sarcomatoid features, approximately 50 patients were identified in each study arm. In comparison with the intention-to-treat population, the percentage of patients with IMDC intermediate/high risk disease was higher in this subgroup. 

The depth of tumor response for patients with measurable disease characterized by sarcomatoid features,  with respective rates for those with tumor shrinkage by 60% or higher (54% vs 16%), 80% or higher (33% vs 8%) and 100% (ie, complete response [CR]; 13% vs 2%) again favoring patients receiving pembrolizumab plus axitinib.  

In the sarcomatoid subgroup, 1-year PFS rates were 57% [combination] and 26% [sunitinib). While median PFS was not reached in the combination arm, it was 8.4 months for patients receiving sunitinib (HR, 0.54; 95% CI, 0.29-1.00). The ORR rates were 58.8% [combination therapy] and 31.5% [sunitinib] in this subgroup. Median OS was not reached in either arm (HR, 0.58, 95% CI, 0.21-1.59). 

In his concluding remarks, Brian Rini, department of hematology and medical oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, who was the study presenter, stated that “pembrolizumab plus axitinib is a new standard of care for first-line treatment of advanced clear cell RCC with OS, PFF, and ORR benefit in all IMDCC risk categories and substantial activity in participants with sarcomatoid RCC.”

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.


  1. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 4500.
  2. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116-1127. 
  3. Pembrolizumab (Keytruda®) [package insert]. Whitehorse Station, NJ: Merck & Co., Inc.; 2019.