Immunotherapy Combo Improves Progression-Free Survival in Untreated Kidney Cancer

Phase 3 data show combination therapy demonstrates clinical benefit as first-line treatment.

Avelumab, an immune checkpoint inhibitor, in combination with axitinib, a tyrosine kinase inhibitor (TKI), significantly improved progression-free survival (PFS) in untreated renal cell carcinoma (RCC), according to clinical trial data presented at the European Society for Medical Oncology (ESMO) 2018 Congress.

The prognosis for patients with advanced RCC is poor, with less than 10% surviving at 5-years post-diagnosis, indicating a need for more effective therapies.

The phase 3 JAVELIN Renal 101 global study evaluated avelumab plus axitinib compared with TKI sunitinib alone in the first-line treatment of advanced RCC in 866 patients. In the trial, 442 patients received avelumab at 10 mg/kg intravenously (IV) every 2 weeks in combination with axitinib, 5 mg orally twice daily. In the comparison group, 444 patients received sunitinib at 50 mg orally once per day for 4 weeks, followed by 2 weeks off treatment.

According to the data, median PFS was 13.8 in the combination arm compared with 7.2 months in the sunitinib arm (HR = 0.61; p < .0001) in patients with programmed cell death-ligand 1 positive (PD-L1+) tumors. Median PFS in patients irrespective of PD-L1 expression was 13.8 months versus 8.4 months (HR = 0.69; p = .0001), respectively. The objective response rate for patients treated with the combination therapy was 55.2 (CI 95%: 49.9, 61.2) compared with 25.5 (CI 95%: 20.6, 30.9).

“TKIs and checkpoint blockers like avelumab, both may have potential immune-modulating functions that, when combined, may provide clinical benefit in patients with advanced RCC that exceeds the effects of the respective drugs alone, without compromising toxicity,” Robert Motzer, presenter and study lead from Memorial Sloan Kettering Cancer Center, said in a press release.

Overall, treatment-emergent adverse events of grade 3 and over were experienced by 71.2% versus 71.5% of patients in the combination versus sunitinib arms, respectively. Adverse events led to discontinuation of drugs in 22.8% in the combination arm versus 13.5% in the sunitinib arm, according to the study.

“The results are eye catching. The response rates are twice as good as previous standards of care, and progression-free survival is entering into very impressive territory for a randomized trial,” professor Thomas Powles, consultant oncologist at Barts Health NHS Trust, said in the release. “This approach involves giving combinations of most active agents upfront, therefore there is uncertainty around whether this will translate into a similarly impressive survival signal, as seen with other immunotherapy combinations.”


Avelumab plus axitinib significantly improve progression-free survival in untreated renal cell carcinoma [ESMO 2018 press release]. European Society for Medical Oncology’s website. Accessed October 22, 2018.