BACKGROUND: Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti-PD-L1) monotherapy in patients with mRCC as either first-line (1 L) or second-line (2 L) treatment. METHODS: Patients with mRCC with a clear-cell component who were treatment naive (1 L subgroup) or had disease progression after one prior line of therapy (2 L subgroup) received avelumab 10 mg/kg intravenous infusion every 2 weeks. Endpoints included confirmed best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), PD-L1 expression, and safety. RESULTS: A total of 62 patients were enrolled in the 1 L subgroup, and 20 patients were enrolled in the 2 L subgroup. In the 1 L and 2 L subgroups, confirmed objective response rates were 16.1 and 10.0%, median DOR was 9.9 months (95% confidence interval [CI], 2.8-not evaluable) and not evaluable (95% CI, 6.9-not evaluable), median PFS was 8.3 months (95% CI, 5.5-9.5) and 5.6 months (95% CI, 2.3-9.6), and median OS was not evaluable (95% CI, not evaluable) and 16.9 months (95% CI, 8.3-not evaluable), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 51 patients in the 1 L subgroup (82.3%) and 14 patients in the 2 L subgroup (70.0%). Grade ≥ 3 TRAEs occurred in eight patients in the 1 L subgroup (12.9%) and one patient in the 2 L subgroup (5.0%). No treatment-related deaths occurred. CONCLUSION: Avelumab showed clinical activity and a manageable safety profile in both the 1 L and 2 L treatment setting in patients with mRCC. These data support the use of avelumab in combination with other agents in mRCC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01772004 ; registered 21 January, 2013.

Centre Oscar Lambret Lille France

General Medical Oncology University Hospitals Leuven Leuven Cancer Institute Leuven Belgium

Genitourinary Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda USA

Global Clinical Development EMD Serono Billerica USA

Haematology Oncology Northwest Medical Specialties Lakewood USA

Horovice Oncology Clinic Nemocnice Rudolfa a Stefanie Benešov a s Benešov Czech Republic

Internal Medicine University of Cincinnati Cincinnati USA

Karmanos Cancer Institute Wayne State University 4100 John R Street Detroit MI 48201 USA

Medical Oncology Bordeaux University Hospital Bordeaux France

Medical Oncology Centre Paul Strauss Centre de Recherche Centres de Lutte Contre le Cancer Strasbourg France

Merck KGaA Darmstadt Germany

Merck Serono Pharmaceutical R and D Co Beijing China

Oncology Haematology Oncology Consultants Houston USA

Zobrazit více v PubMed

American Cancer Society. What is kidney cancer? 2017. https://www.cancer.org/cancer/kidney-cancer/about/what-is-kidney-cancer.html. Accessed 04 March 2019.

Surveillance, Epidemiology, And end results program. Cancer Stat Facts: kidney and renal pelvis cancer https://seer.cancer.gov/statfacts/html/kidrp.html. Accessed 04 March 2019.

Penticuff JC, Kyprianou N. Therapeutic challenges in renal cell carcinoma. Am J Clin Exp Urol. 2015;3(2):77–90. PubMed PMC

Blanco AI, Teh BS, Amato RJ. Role of radiation therapy in the management of renal cell cancer. Cancers (Basel) 2011;3(4):4010–4023. PubMed PMC

Choueiri TK, Motzer RJ. Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med. 2017;376(4):354–366. PubMed

Hutson TE. Targeted therapies for the treatment of metastatic renal cell carcinoma: clinical evidence. Oncologist. 2011;16(Suppl 2):14–22. PubMed PMC

Thomas JS, Kabbinavar F. Metastatic clear cell renal cell carcinoma: a review of current therapies and novel immunotherapies. Crit Rev Oncol Hematol. 2015;96(3):527–533. PubMed

Ross K, Jones RJ. Immune checkpoint inhibitors in renal cell carcinoma. Clin Sci (Lond) 2017;131(21):2627–2642. PubMed PMC

Webb ES, Liu P, Baleeiro R, Lemoine NR, Yuan M, Wang Y. Immune checkpoint inhibitors in cancer therapy. J Biomed Res. 2018;32(5):317–326. PubMed PMC

Iacovelli R, Nolè F, Verri E, Renne G, Paglino C, Santoni M, et al. Prognostic role of PD-L1 expression in renal cell carcinoma: a systematic review and meta-analysis. Target Oncol. 2016;11(2):143–148. PubMed

Wang Z, Peng S, Xie H, Guo L, Cai Q, Shang Z, et al. Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals. Clin Exp Med. 2018;18(2):165–175. PubMed

Thompson RH, Dong H, Kwon ED. Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy. Clin Cancer Res. 2007;13(2):709s–715s. PubMed

Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal cell carcinoma. N Engl J Med. 2015;373(19):1803–1813. PubMed PMC

Motzer RJ, Tannir NM, McDermott DF, Frontera OS, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–1290. PubMed PMC

Heery CR, O’Sullivan-Coyne G, Madan RA, Cordes L, Rajan A, Rauckhorst M, et al. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 2017;18(5):587–598. PubMed PMC

Bavencio (avelumab) [package insert]. Rockland, MA: EMD Serono; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761049s000lbl.pdf. Accessed 14 May 2019.

Gulley JL, Rajan A, Spigel DR, Iannotti N, Chandler J, Wong DJL, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):599–610. PubMed PMC

Disis ML, Taylor MH, Kelly K, Beck JT, Gordon M, Moore KM, et al. Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN Solid Tumor trial. JAMA Oncol. 2019;5(3):393–401. PubMed PMC

Patel MR, Ellerton J, Infante JR, Agrawal M, Gordon M, Aljumaily R, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol. 2018;19(1):51–64. PubMed PMC

Hassan R, Thomas A, Nemunaitis JJ, Patel MR, Bennouna J, Chen FL, et al. Efficacy and safety of avelumab treatment in patients with advanced unresectable mesothelioma: phase 1b results from the JAVELIN Solid Tumor trial. JAMA Oncol. 2019;5(3):351–357. PubMed PMC

Chung HC, Arkenau H-T, Lee J, Rha SY, Oh D-Y, Wyrwicz L, et al. Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019;7(1):30. PubMed PMC

Le Tourneau C, Hoimes C, Zarwan C, Wong DJ, Bauer S, Claus R, et al. Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2018;6(1):111. PubMed PMC

Keilholz U, Mehnert JM, Bauer S, Bourgeois H, Patel MR, Gravenor D, et al. Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019;7(1):12. PubMed PMC

Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–1127. PubMed

Choueiri TK, Larkin J, Oya M, Thistlethwaite F, Martignoni M, Nathan P, et al. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 2018;19(4):451–460. PubMed

Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103–1115. PubMed PMC

Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, et al. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018;19(3):405–415. PubMed PMC

McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, 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;24(6):749–757. PubMed PMC

Donskov F, McDermott DF, Lee JL, Szczylik C, Malik J, Alekseev BY, et al. KEYNOTE-427 cohort A: pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (ccRCC) Ann Oncol. 2018;29(Suppl 8):viii303–viii331.

Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet Oncol. 2019;19(1):51–64. PubMed

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01772004