University of Chicago Comprehensive Cancer Center, Chicago, IL
Peter H. O'Donnell , Jonathan E. Rosenberg , Christopher J. Hoimes , Daniel P. Petrylak , Matthew I. Milowsky , Rana R. McKay , Sandy Srinivas , Terence W. Friedlander , Chethan Ramamurthy , Mehmet Asim Bilen , Earle F Burgess , Nataliya Mar , Helen Moon , Daniel M. Geynisman , Saby George , Anne-Sophie Carret , Yao Yu , Maria Guseva , Blanca Homet Moreno , Thomas W. Flaig
Background: In EV-103 Cohort K (NCT03288545), EV and P in combination (EV+P) showed encouraging antitumor activity and a manageable safety profile when used as 1L therapy in patients (pts) w/ la/mUC who are ineligible for cisplatin, a population w/ high unmet need. Here we report results of an analysis of prespecified Cohort K subgroups known to be associated w/ poor outcomes. Methods: Pts who are cisplatin-ineligible w/ previously untreated la/mUC were randomized 1:1 to EV (1.25 mg/kg) as monotherapy on Days 1 and 8 or in combination w/ P (200 mg) on Day 1 of 3-week cycles. Primary endpoint is cORR per RECIST v1.1 by blinded independent central review w/ no formal statistical comparison between arms. Secondary endpoints included duration of response and safety (e.g. treatment-related adverse events, TRAEs). The cORR analysis was performed in prespecified subgroups including age, ECOG PS, liver metastasis, PD-L1 expression status, metastatic disease site at baseline, and primary disease site of origin. Results: 149 pts were treated: EV+P n=76; EV n=73; cORRs across key subgroups for both EV+P and EV monotherapy are shown in the table. For EV+P overall cohort, cORR (95%CI): 64.5% (52.7, 75.1); median DOR was not reached. cORRs were consistent across subgroups for EV+P including those w/ ECOG PS score of 1-2: 62.8% (46.7, 77.0) and presence of liver metastasis: 53.8% (25.1, 80.8). Among TRAEs of special interest in the EV+P arm, skin reactions occurred in n=51 (67.1%); peripheral neuropathy occurred in n=46 (60.5%). For EV+P, 68.4% of pts had TRAEs leading to interruption of either EV or P; 48.7% of pts had TRAEs leading to EV dose reduction. Median duration of EV+P treatment was 11 cycles. Conclusions: EV+P showed promising cORR in 1L cisplatin-ineligible pts w/ la/mUC; activity was consistently observed across a range of pre-specified subgroups including those with poor prognosis. EV+P TRAEs were manageable w/ close monitoring and appropriate dose modifications w/ a meaningful duration of treatment. EV+P has the potential to address high unmet needs in 1L la/mUC and MIBC and is being further evaluated in 3 Phase 3 trials (NCT04223856, NCT04700124, NCT03924895). Clinical trial information: NCT03288545.
cORR by Subgroup, % (95% CI) | EV + P (n=76) | n/N | EV Monotherapy (n=73) | n/N |
---|---|---|---|---|
Overall | 64.5 (52.7, 75.1) | 49/76 | 45.2 (33.5, 57.3) | 33/73 |
Age ≥ 65 years | 64.4 (50.9, 76.4) | 38/59 | 48.4 (35.5, 61.4) | 30/62 |
ECOG PS = 1-2 | 62.8 (46.7, 77.0) | 27/43 | 44.4 (29.6, 60.0) | 20/45 |
Visceral metastases1 | 65.6 (52.7, 77.1) | 42/64 | 46.7 (33.7, 60.0) | 28/60 |
Liver metastasis = Yes | 53.8 (25.1, 80.8) | 7/13 | 53.8 (25.1, 80.8) | 7/13 |
Upper tract primary disease site of origin | 60.0 (40.6, 77.3) | 18/30 | 42.9 (21.8, 66.0) | 9/21 |
PD-L1 expression CPS <10 | 61.4 (45.5, 75.6) | 27/44 | 50.0 (33.4, 66.6) | 19/38 |
1Includes liver metastases.
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Abstract Disclosures
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