ESMO 2019: Phase 3 JAVELIN Renal 101 Trial of First-Line Avelumab + Axitinib vs. Sunitinib For Advanced Renal Cell Carcinoma

Barcelona, Spain ( The role of upfront cytoreductive nephrectomy (uCN) in patients with metastatic renal cell carcinoma (mRCC) is currently under debate as systemic therapy alone (sunitinib) was recently demonstrated to be noninferior.1 Since that time, combination immunotherapy and immunotherapy plus VEGF tyrosine kinase inhibitor (TKI) combination regimens have demonstrated efficacy in patients with previously-untreated mRCC. JAVELIN Renal 101 demonstrated a significant improvement in progression-free survival (PFS) with avelumab plus axitinib (A + Ax) versus sunitinib (median PFS 13.8 vs 8.4 months, HR 0.69, p < 0.001) in patients with previously untreated clear cell mRCC.2 Clinical benefit was seen in patients irrespective of prior uCN. The efficacy of this therapy on the primary tumor is unknown. In this abstract, the investigators report findings from a post hoc analysis of patients enrolled in JAVELIN Renal 101 with renal target lesions who had not undergone uCN. 

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Of 886 patients in the study, 20.2% did not undergo uCN (90 in the A + Ax arm, 89 in the sunitinib arm). Of these patients, 117 had renal target lesions at baseline: 55/90 and 62/89, respectively. Baseline characteristics in this subgroup were well balanced – in both groups, approximately 60% were IMDC intermediate risk (the remaining 40% were poor risk) and the median size of the primary renal lesion was approximately 8.5 cm.

The confirmed objective response rate (ORR) in all lesions was higher in the A + Ax arm (32.7%) than the sunitinib arm (11.3%). The percentage of patients with > 30% shrinkage in the renal target lesions from baseline was 34.5% in the A + Ax arm compared to 9.7% in the sunitinib arm. The median tumor shrinkage from baseline in renal target lesions was -21.1% in the combination arm versus -10.0% in the sunitinib arm. Any shrinkage from baseline in renal target lesions was observed in 90.9% of patients receiving A + Ax compared to 72.6% receiving sunitinib.

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A + Ax improved PFS in patients who did not undergo uCN versus sunitinib when assessed in either the renal target lesions or in all lesions. The median OS was not reached in either arm, but the HR for A + Ax compared to sunitinib is 0.62 (0.32-1.29).
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The investigators then performed immune biomarker analyses. Compared with patients in the overall population who underwent uCN, patients in this subgroup who did not undergo uCN had reduced PD-L1 expression. Gene expression analyses revealed treatment arm-specific differences in PFS with the IMmotion 150 T effector gene signature favoring the combination arm and the IMmotion 150 angiogenesis arm favoring the sunitinib arm.3

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This study is the first report of the efficacy of immunotherapy plus VEGF TKI combination on the primary renal tumor in the context of mRCC and provides important insights into future neoadjuvant strategies in RCC. An ongoing open-label, single-arm, phase 2 trial (NCT03341845) is investigating avelumab plus axitinib as neoadjuvant therapy in patients with localized RCC.

Presented by: Laurence Albiges, MD, PhD, Medical Oncologist at the Gustave Roussy Institute

Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, Twitter: @jberchuck at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept - 1 Oct 2019 in Barcelona, Spain

1. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018 Aug 2;379(5):417-427.
2. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1103-1115.
3. McDermott DF, Huseni MA, Atkins MB, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018 Jun;24(6):749-757.

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