e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Avelumab first-line maintenance plus best supportive care vs best supportive care alone for advanced urothelial carcinoma: JAVELIN Bladder 100 subgroup analysis based on duration and cycles of first-line chemotherapy (#245)

Thomas Powles 1 , Yohann Loriot 2 , Miguel A Climent Durán 3 , Srikala Sridhar 4 , Joaquim Bellmunt 5 , Daniel P Petrylak 6 , Jing Wang 7 , Nuno Costa 8 , Robert Laliberte 7 , Alessandra di Pietro 9 , Petros Grivas 10 , Cora N Sternberg 11
  1. Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, London, United Kingdom
  2. Gustave Roussy, INSERMU981, Université Paris-Saclay, Villejuif, France
  3. Instituto Valenciano de Oncología, Valencia, Spain
  4. Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada
  5. Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts, United States
  6. Yale Cancer Center, New Haven, Connecticut, United States
  7. Pfizer, Cambridge, Massachusetts, United States
  8. Pfizer, Porto Salvo, Portugal
  9. Pfizer srl, Milano, Italy
  10. University of Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, Washington, United States
  11. Englander Institute for Precision Medicine, Weill Cornell Medicine, Hematology/Oncology, New York, United States

Aims: In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab first-line maintenance significantly prolonged overall survival (OS) vs best supportive care (BSC) in patients with advanced urothelial carcinoma (UC) that had not progressed with first-line platinum-based chemotherapy. Optimal duration of first-line chemotherapy is unknown. We report a post hoc analysis of efficacy by duration or number of cycles of first-line chemotherapy.

Methods: Patients with unresectable locally advanced or metastatic UC without disease progression with 4-6 cycles of first-line platinum-based chemotherapy were randomized to receive avelumab 1L maintenance + BSC or BSC alone. Subgroups were defined by quartiles (Q) for duration (<Q1 [<15.0 weeks], Q1-Q2 [15.0 to <18.0 weeks], Q2-Q3 [18.0 to <20.1 weeks], and >Q3 [>20.1 weeks]) or estimated number of cycles (4, 5, or 6) of first-line chemotherapy. Duration included dosing delays/interruptions; the decision to stop chemotherapy was at the investigator’s discretion.

Results: Patient numbers within subgroups were generally balanced between arms. An OS benefit was observed for avelumab + BSC vs BSC alone across subgroups. In the <Q1, Q1-Q2, Q2-Q3, and >Q3 subgroups, HRs for OS were 0.65 (95% CI: 0.418, 1.021), 0.79 (95% CI: 0.499, 1.267), 0.74 (95% CI: 0.499, 1.096), and 0.63 (95% CI: 0.394, 1.003), respectively. In the 4, 5, and 6 cycles subgroups, HRs for OS were 0.69 (95% CI: 0.481, 1.000), 0.98 (95% CI: 0.568, 1.707), and 0.66 (95% CI: 0.472, 0.915), respectively. A progression-free survival benefit was also observed for avelumab + BSC vs BSC alone across subgroups. No significant treatment-by-cycle interaction (at 0.05 level) was observed.

Conclusions: Improved OS was observed with avelumab first-line maintenance vs BSC alone irrespective of duration or cycles of first-line chemotherapy received prior to randomization. Among patients who were unable to receive 6 cycles of first-line chemotherapy, avelumab first-line maintenance also provided an OS benefit.