Ramucirumab in patients with advanced HCC and elevated alpha-fetoprotein (AFP): Outcomes by treatment-emergent ascites.

4644 Background: REACH and REACH-2 investigated ramucirumab (RAM) vs placebo (PL) in patients (pts) with advanced HCC following sorafenib, with REACH-2 enrolling only pts with baseline AFP ≥400 ng/mL. Ascites is common in HCC and associated with poorer outcomes. An exploratory analysis of outcomes by treatment-emergent (TE)-ascites was done. Methods: Pts with HCC, Child-Pugh A, ECOG PS ≤1, prior sorafenib, and no clinically meaningful ascites were randomized (REACH 1:1; REACH-2 2:1) to RAM 8 mg/kg or PL Q2W. A pooled meta-analysis of independent pt data (stratified by study) from REACH-2 and REACH (AFP ≥400 mg/mL) was done. OS and PFS were evaluated by Kaplan-Meier estimator and Cox models. Prognosis of TE-ascites in OS was evaluated by multivariate Cox models (adjusted for baseline ECOG PS, AFP, macrovascular invasion (MVI), and treatment [trt]). Results: Baseline characteristics were generally balanced between TE-ascites and non-ascites pts; however, more pts with ascites had MVI at baseline. Any-grade ascites was reported at a higher rate in RAM than PL (66 [21%] vs 33 [15%] pts, respectively), with most being low grade. Rate of Gr ≥3 ascites was similar between arms (15 [5%] vs 9 [4%] pts). Median time to onset (43 vs 47 days) and median duration of ascites (13 vs 18 days) were similar in RAM vs PL, with furosemide (22%) and spironolactone (19%) as most common trt and paracentesis (18%) as most common procedure for ascites in both arms. Ascites trended as a prognostic factor for OS after adjustment (with vs without; HR=1.3, 95% CI: 0.99, 1.62). Ascites was more commonly linked with hypoalbuminemia (odds ratio 4.9, 95% CI: 2.5, 9.3), but was not associated with proteinuria or hypertension. TEAEs occurred more frequently in pts with ascites in both arms. The most frequent Gr ≥3 TEAE in pts with ascites was hypertension. One RAM pt discontinued trt due to ascites. RAM trt was beneficial irrespective of presence of ascites (Table), and pts with ascites received more post-discontinuation therapy on RAM than PL (18% vs 6%). Conclusions: Acknowledging limitations of sample size, RAM provided a survival benefit in pts who did or did not experience TE-ascites. RAM was well tolerated and no new safety findings were observed. Clinical trial information: NCT011400347; NCT02435433 . [Table: see text]