The Christie NHS Foundation Trust, Manchester, United Kingdom
Juan W. Valle , Li-Yuan Bai , Rashida Orlova , Eric Van Cutsem , Jorge Adeva Alfonso , Li-Tzong Chen , Radka Obermannova , Thomas Jens Ettrich , Jen-Shi Chen , Harpreet Singh Wasan , Crystal S. Denlinger , Arndt Vogel , Aiwu Ruth He , Nathalie Bousmans , Allicia C Girvan , Wei Zhang , Richard A. Walgren , Roberto Carlesi , Do-Youn Oh
Background: We assessed RAM or MER plus standard of care GEM+CIS as first-line treatment for BTC. Methods: Patients (pts) with BTC, ECOG PS 0/1, and measurable disease were randomized 2:1:2:1 to oral MER 80 mg QD, oral PL QD, IV RAM 8 mg/kg days 1 and 8 Q3W or IV PL days 1 and 8 Q3W. Pts also received up to 8 cycles IV GEM 1000 mg/m2 + CIS 25 mg/m2 days 1 and 8 Q3W. RAM, MER, or PL could continue until disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall survival (OS), objective response rate (ORR), and safety. PFS and hazard ratios (HRs) were compared using stratified log-rank tests and Cox regression models, respectively. NCT02711553. Results: 309 pts were randomized to RAM (106), MER (102), or pooled PL (101). More pts in the RAM (54.7%) and MER (49.0%) groups had baseline ECOG PS 1 vs PL (38.6%). Efficacy endpoints are in Table. Fewer pts received post-discontinuation systemic therapy in the RAM group (RAM 37.5%, MER 50.0%, PL 52.0%). The most common grade ≥3 treatment-emergent adverse events were: RAM vs PL: neutropenia (49.0% vs 33.0%), thrombocytopenia (34.6% vs 17.0%), and anemia (26.9% vs 19.0%); MER vs PL: neutropenia (47.1% vs 33.0%), thrombocytopenia (18.6% vs 17.0%), and alanine aminotransferase increased (10.8% vs 5.0%). Conclusions: PFS, OS, and ORR were not improved with the addition of RAM or MER to GEM+CIS. Treatment was well tolerated, with safety profiles consistent with known profiles for RAM, MER, and GEM+CIS. Translational studies are ongoing. Clinical trial information: NCT02711553.
RAM+GEM+CIS (N=106) | MER+GEM+CIS (N=102) | PL+GEM+CIS (N=101) | |
---|---|---|---|
Median PFS, mo (80% CI) | 6.47 (5.65 – 7.13) | 6.97 (6.21 – 7.13) | 6.64 (5.59 – 6.83) |
HR vs PL (80% CI) | 1.123 (0.904 – 1.395) | 0.920 (0.734 – 1.153) | |
P-value vs PL | 0.4821 | 0.6417 | |
Median OS, mo (95% CI) | 10.45 (8.48 – 11.76) | 14.03 (11.96 – 16.36) | 13.04 (11.40 – 15.31) |
HR vs PL (95% CI) | 1.336 (0.959 – 1.862) | 0.948 (0.669 – 1.342) | |
P-value vs PL | 0.0870 | 0.7599 | |
ORR, n (%; 95% CI) | 33 (31.1; 22.3 – 39.9) | 20 (19.6; 11.9 – 27.3) | 33 (32.7; 23.5 – 41.8) |
Odds ratio vs PL (95% CI) | 1.0 (0.6 – 1.9) | 0.5 (0.2 – 0.9) | |
P-value vs PL | 0.8779 | 0.0235 |
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