Estimated net benefit of avelumab (AVE) + best supportive care (BSC) vs BSC alone for patients (pts) with advanced urothelial carcinoma (aUC) using a quality-adjusted time without cancer symptoms or toxicity (Q-TWiST) analysis.

person Thomas Powles Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London, United Kingdom info_outline Thomas Powles, Paul Cislo, Melissa Kirker, Jane Chang, Norbek Gharibian, Allison Thompson, Nuno Costa, Petros Grivas

Authors person Thomas Powles Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London, United Kingdom info_outline Thomas Powles, Paul Cislo, Melissa Kirker, Jane Chang, Norbek Gharibian, Allison Thompson, Nuno Costa, Petros Grivas Organizations Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London, United Kingdom, Pfizer, New York, NY, Pfizer, Porto Salvo, Portugal, University of Washington; Fred Hutchinson Cancer Center, Seattle, WA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company This study was sponsored by Pfizer, as part of an alliance between Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) Background: The JAVELIN Bladder 100 (JB-100) trial (NCT02603432) showed that treatment with AVE first-line maintenance (1LM) + BSC significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC that had not progressed after 1L platinum-based chemotherapy. Safety and patient-reported outcomes (PROs) were previously reported. This post hoc analysis used JB-100 data to assess between-treatment differences using a Q-TWiST analysis, an integrated measure that incorporates efficacy, safety, and PROs into a single value. Methods: Mean OS was partitioned into 3 health states: time with all-cause grade ≥3 toxicity (TOX) prior to progression, time without all-cause grade ≥3 toxicity or symptoms of disease progression (TWiST), and time after progression or relapse (REL). To ensure equal observation time for each arm, analysis time was restricted to a period of 47.7 months from randomization, which was the shorter follow-up time between arms. A range of utility values were explored and weighted by the time in each health state then summed to estimate Q-TWiST to account for differences in quality of life. Mean between-treatment differences for each health state were also calculated. Bootstrap methods were used to estimate CIs for means and difference between means. Results: Time in TOX was slightly longer with AVE + BSC vs BSC alone; however, time spent in TWiST was much longer with AVE + BSC. Time in REL with AVE + BSC appears shorter vs BSC alone because pts experienced more time in the progression-free state, which led to less time in REL. Regardless of the range of utility values explored for each health state, the Q-TWIST estimate was always longer with AVE + BSC, with mean differences ranging from 3.7 to 7.1 months (95% CI not including 1). Conclusions: Pts receiving AVE + BSC demonstrated a consistently longer Q-TWiST (vs BSC alone), indicating a net benefit. Pts receiving AVE + BSC achieved greater quality-adjusted time by progressing more slowly (shorter REL) and living longer (greater OS). The Q-TWiST advantage reflects the safety profile of AVE in the context of a survival benefit. Restricted health state durations in months (mean, 95% CI). Clinical trial information: NCT02603432. AVE + BSC n=350 BSC alone n=350 AVE + BSC − BSC alone TOX 1.81 (1.346, 2.196) 1.19 (0.761, 1.602) 0.61 (−0.013, 1.204) TWiST 11.98 (10.722, 13.202) 5.52 (4.516, 6.530) 6.46 (4.824, 8.194) REL 12.99 (11.821, 14.087) 15.72 (14.495, 16.993) −2.74 (−4.593, −1.115) PFS 13.79 (12.446, 15.102) 6.71 (5.771, 7.631) 7.07 (5.367, 8.802) OS 26.77 (25.384, 28.165) 22.44 (21.089, 23.758) 4.34 (2.398, 6.236) Note: Progression data are based on investigator assessment.

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