Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in subgroups defined by response to 1L chemotherapy.

person Begoña Pérez-Valderrama Hospital Universitario Virgen del Rocío, Seville, Spain info_outline Begoña Pérez-Valderrama, Thomas Powles, Srikala S. Sridhar, Claudia Caserta, Yohann Loriot, Shilpa Gupta, Joaquim Bellmunt, Cora N. Sternberg, Jing Wang, Nuno Costa, Robert J Laliberte, Alessandra Di Pietro, Se Hoon Park, Petros Grivas

Authors person Begoña Pérez-Valderrama Hospital Universitario Virgen del Rocío, Seville, Spain info_outline Begoña Pérez-Valderrama, Thomas Powles, Srikala S. Sridhar, Claudia Caserta, Yohann Loriot, Shilpa Gupta, Joaquim Bellmunt, Cora N. Sternberg, Jing Wang, Nuno Costa, Robert J Laliberte, Alessandra Di Pietro, Se Hoon Park, Petros Grivas Organizations Hospital Universitario Virgen del Rocío, Seville, Spain, Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew’s Hospital, London, United Kingdom, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada, Medical Oncology Unit, Azienda Ospedaliera S. Maria, Terni, Italy, Gustave Roussy, DITEP, Université Paris-Saclay, Villejuif, France, Cleveland Clinic, Cleveland, OH, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, MA, Englander Institute for Precision Medicine, New York, NY, Pfizer, Cambridge, MA, Pfizer, Porto Salvo, Portugal, Pfizer srl, Milan, Italy, Sungkyunkwan University Samsung Medical Center, Seoul, South Korea, University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Pharmaceutical/Biotech Company Background: In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with aUC that had not progressed with 1L platinum-based chemotherapy. We report exploratory analyses in subgroups defined by response to 1L chemotherapy (complete response [CR], partial response [PR], or stable disease [SD]) after ≥2 years of follow-up. Methods: Eligible pts had unresectable locally advanced or metastatic UC without progression with 4-6 cycles of 1L gemcitabine + cisplatin or carboplatin. Pts were randomized 1:1 to receive avelumab + BSC (n = 350) or BSC alone (n = 350), stratified by best response to 1L chemotherapy (CR/PR vs SD) and visceral vs nonvisceral disease at start of 1L chemotherapy. Results: At data cutoff (June 4, 2021), median follow-up in both arms was ≥38 months. OS and PFS were longer in the avelumab + BSC vs BSC alone arm in all subgroups (Table). Median duration of study treatment and incidence of grade ≥3 treatment-emergent adverse events (TEAEs) in subgroups are shown in the Table. In the avelumab + BSC vs BSC alone arm, respectively, subsequent second-line anticancer drug therapy was received by: CR subgroup, 50.0% vs 74.2%; PR subgroup, 58.3% vs 71.8%; and SD subgroup, 46.4% vs 70.4%. Conclusions: Long-term follow-up from JAVELIN Bladder 100 continues to show prolonged OS and PFS with avelumab + BSC vs BSC alone irrespective of response (CR, PR, or SD) to 1L chemotherapy and despite a higher proportion of pts in the BSC alone arm receiving subsequent therapy. Long-term safety was consistent across subgroups. These findings further support avelumab 1L maintenance as standard of care for all pts with aUC that has not progressed with 1L platinum-based chemotherapy. Clinical trial information: NCT02603432. Response to 1L chemotherapy CR (n = 179) PR (n = 326) SD (n = 195) Arm Avelumab + BSC (n = 90) BSC (n = 89) Avelumab + BSC (n = 163) BSC (n = 163) Avelumab + BSC (n = 97) BSC (n = 98) Study treatment ongoing, % 13.3 6.7 12.9 0.6 10.3 3.1 Median OS (95% CI), mo 39.8 (28.5-not evaluable) 26.8 (18.5-33.6) 19.2 (16.0-23.8) 12.8 (10.3-14.8) 22.3 (18.2-28.8) 14.0 (10.6-19.6) HR for OS (95% CI) 0.72 (0.482-1.076) 0.70 (0.541-0.914) 0.84 (0.596-1.188) Median PFS by investigator (95% CI), mo 9.5 (5.7-16.6) 5.1 (3.0-5.7) 3.8 (3.7-5.6) 1.9 (1.9-2.1) 5.6 (3.7-7.5) 2.0 (1.9-3.6) HR for PFS (95% CI) 0.58 (0.410-0.817) 0.47 (0.367-0.607) 0.59 (0.421-0.816) Median duration of study treatment (range), wk* 33.8 (2.0-214.4) 24.1 (0.1-168.4) 22.2 (2.0-213.1) 12.3 (0.1-231.7) 25.1 (2.0-216.0) 12.3 (0.1-164.0) Grade ≥3 TEAE, %* 51.1 16.9 51.9 27.0 59.6 32.0 *In treated pts