Multiple analyses from the JAVELIN clinical development program assessing avelumab (Bavencio, Merck KGaA) alone or as part of combination regimens for the treatment of advanced cancers, including renal cell carcinoma (RCC), metastatic Merkel cell carcinoma (mMCC), and certain other solid tumors were presented at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain.

The data presented at the conference included 3 subgroup analyses of the phase 3 JAVELIN Renal 101 study (NCT02684006), a randomized, multicenter, open-label study of avelumab in combination with axitinib. The study included 886 patients with untreated advanced RCC from patients across all International Metastatic RCC Database Consortium risk groups.

The results, published in The New England Journal of Medicine, demonstrated that avelumab in combination with axitinib significantly improved progression-free survival compared with sunitinib in patients with advanced RCC, and had a generally acceptable safety tolerability profile, including serious adverse events. The study included patients who did not undergo cytoreductive nephrectomy.

In a presentation of the data on Sunday, September 29, a post-hoc analysis showed that patients with advanced RCC who were treated with avelumab plus axitinib who did not undergo cytroreductive nephrectomy experienced greater shrinkage of the primary renal tumor versus sunitinib (≥30% shrinkage for best percent change in renal target lesions from baseline in 34.5% versus 9.7%, respectively). Patients without prior cytoreductive nephrectomy comprised 20% of the patients in the study. 

A separate subgroup analysis of patients with advanced RCC with sarcomatoid histology, an aggressive sutype of RCC, demonstrated that avelumab plus axitinib improved PFS and objective response rate (ORR) versus sunitinib in patients (median PFS: 7 months versus 4 months, HR 0.57 [95% CI, 0.325-1.003]; median ORR: 46.8% versus 21.3%). 

Additionally, another subgroup analysis of Japanese patients with advanced RCC showed that avelumab plus axitinib improved PFS compared with sunitinib in this population as well, regardless of PD-L1 expression (16.6 months versus 11.2 months, respectively; HR, 0.66 [95% CI, 0.30-1.46]). Common treatment-emergent adverse events in each arm included hand-foot syndrome, hypertension, and platelet count decreased. 

In May 2019, the FDA approved avelumab in combination with axitinib for the first-line treatment of patients with advanced RCC. The Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion recommending approval of avelumab in combination with axitinib for the first-line treatment of adult patients with advanced RCC in September 2019. 

The results of the new analyses are consistent with findings from the overall JAVELIN Renal 101 study populations and provide a better understanding of the combination in a broad range of patients with advanced RCC, according to the press release.

Reference
  1. New Data for BAVENCIO (avelumab) for Advanced Cancers to be presented at ESMO 2019 [press release]. Pfizer website. Darmstadt, Germany. Published September 27, 2019. https://www.pfizer.com/news/press-release/press-release-detail/new_data_for_bavencio_avelumab_for_advanced_cancers_to_be_presented_at_esmo_2019. Accessed September 27, 2019.