Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis.

Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1). We report ≥2-year follow-up data for avelumab treatment and exploratory subgroup analyses in patients with urothelial carcinoma. Patients with previously treated advanced/metastatic urothelial carcinoma, pooled from two cohorts of the phase Ib JAVELIN Solid Tumor trial, received avelumab 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity or withdrawal. End points included best overall response and progression-free survival (PFS) per RECIST V.1.1, overall survival (OS) and safety. Post hoc analyses included objective response rates (ORRs) in subgroups defined by established high-risk/poor-prognosis characteristics and association between time to response and outcome. 249 patients received avelumab; efficacy was assessed in 242 postplatinum patients. Median follow-up was 31.9 months (range 24-43), and median treatment duration was 2.8 months (range 0.5-42.8). The confirmed ORR was 16.5% (95% CI 12.1% to 21.8%; complete response in 4.1% and partial response in 12.4%). Median duration of response was 20.5 months (95% CI 9.7 months to not estimable). Median PFS was 1.6 months (95% CI 1.4 to 2.7 months) and the 12-month PFS rate was 16.8% (95% CI 11.9% to 22.4%). Median OS was 7.0 months (95% CI 5.9 to 8.5 months) and the 24-month OS rate was 20.1% (95% CI 15.2% to 25.4%). In post hoc exploratory analyses, avelumab showed antitumor activity in high-risk subgroups, including elderly patients and those with renal insufficiency or upper tract disease; ORRs were numerically lower in patients with liver metastases or low albumin levels. Objective response achieved by 3 months versus later was associated with longer OS (median not reached (95% CI 18.9 months to not estimable) vs 7.1 months (95% CI 5.2 to 9.0 months)). Safety findings were consistent with previously reported 6-month analyses. After ≥2 years of follow-up, avelumab showed prolonged efficacy and acceptable safety in patients with platinum-treated advanced/metastatic urothelial carcinoma, including high-risk subgroups. Survival appeared longer in patients who responded within 3 months. Long-term safety findings were consistent with earlier reports with avelumab treatment in this patient population.

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Competing interests: ABA has no relationships to disclose. JAE has no relationships to disclose. JRI has received research funding from Aileron Therapeutics, ARMO BioSciences, AstraZeneca, BioMed Valley Discoveries, Bristol Myers Squibb, Calithera Biosciences, Celldex, eFFECTOR Therapeutics, Genentech/Roche, GlaxoSmithKline, Immunocore, Janssen Oncology, MedImmune, Merck and Co., Novartis, Pfizer, Phosplatin Therapeutics, Roche, and TESARO. MA has no relationships to disclose. MSG reports having stocks and other ownership interests in Caremission and WCCT Global; has received research funding from AbbVie, Acetylon, Aduro Biotech, Advaxis, Amgen, Array BioPharma, BeiGene, BioLineRx, Calithera Biosciences, CanBas, Celgene, Celldex, Corcept Therapeutics, CtyomX Therapeutics, Deciphera, Driver Group, Endocyte, ESSA, Five Prime Therapeutics, FujiFilm, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Halozyme, Hengrui Therapeutics, Inanovate, Incyte, Lilly, Lilly/ImClone, MabVax, Macrogenics, MedImmune, Merck KGaA (Darmstadt, Germany), Merrimack, Millennum, Minneamrita Therapeutics, Nektar, Novartis, Novita Pharmaceuticals, OncoMed, Pfizer, Phoenix Biotech, Plexxikon, Proderm IQ, Samumed, Seattle Genetics, Sirtex Medical, Strategia Therapeutics, Syndax, SynDevRx, TESARO, Tokai Pharmaceuticals, Tolero Pharmaceuticals, Toray Industries, TRACON Pharma, Trovagene, and Verastem; and reports patents, royalties or other intellectual property for patient-on-patient selection for clinical trials. RA has no relationships to disclose. TG has received research funding from Ferring Pharmaceuticals. LD has no relationships to disclose. K-WL has received research funding from Array BioPharma, ASLAN Pharmaceuticals, AstraZeneca/MedImmune, Five Prime Therapeutics, Green Cross Corp., LSK BioPharma, MacroGenics, Merck KGaA (Darmstadt, Germany), MSD, Ono Pharmaceutical, Pfizer, and Pharmacyclics. MHT reports serving as a consultant or advisor for ArQule, Array BioPharma, Bayer, Blueprint Medicines, Bristol Myers Squibb, Eisai, Loxo, and Novartis; and is a member of a speaker’s bureau for Bristol Myers Squibb, and Eisai. PS reports serving as a consultant or advisor for Blueprint Medicines, Eisai, Ellipses Pharma, Epizyme, Ipsen, Lilly, Loxo, PIQUR Therapeutics, and Plexxikon; and has received research funding from Blueprint Medicines, Boehringer Ingelheim, CoBioRes, Eisai, Exelixis, G1 Therapeutics, Lilly, Novartis, PharmaMar, and Plexxikon. DW reports serving as a consultant or advisor for Merck and Co.; and has received reimbursement for travel, accommodation and expenses from Merck and Co. AR has received honoraria from Bristol Myers Squibb, Ipsen, Merck KGaA (Darmstadt, Germany), MSD, Novartis, and Pfizer; reports serving as a consultant or advisor for Bristol Myers Squibb, Ipsen, Novartis, Pfizer, and Roche; has received research funding from Novartis and Pfizer; and has received reimbursement for travel, accommodation and expenses from Bristol Myers Squibb, MSD, Novartis, and Pfizer. JM reports employment at EMD Serono Research & Development Institute, Inc.; a business of Merck KGaA, Darmstadt, Germany. GP reports employment at EMD Serono, Inc.; a business of Merck KGaA, Darmstadt, Germany. MR reports employment at EMD Serono Research & Development Institute, Inc.; a business of Merck KGaA, Darmstadt, Germany. JLG has received research funding from Astellas/Medivation, Bavarian Nordic, Bristol Myers Squibb, EMD Serono (a business of Merck KGaA, Darmstadt, Germany), Incyte, Janssen, Merck & Co, Immunity Bio, and Pfizer. MRP is a member of a speaker’s bureau for Celgene, Exelixis, Genentech/Roche, and Taiho Pharmaceutical.