Ramucirumab for patients with advanced hepatocellular carcinoma and elevated alpha fetoprotein following a non-sorafenib based systemic therapy: interim results from an expansion cohort of the phase 3 REACH-2 study

Introduction Ramucirumab (IgG1 VEGFR-2 antagonist) is the first and only treatment approved in a biomarker-selected population with advanced hepatocellular carcinoma (HCC) population. The approval was based on data from the phase 3 REACH (NCT01140347) and REACH-2 (NCT02435433) trials. Similar to other contemporary trials, REACH/REACH-2 did not include patients who received first-line therapy other than sorafenib, which was the only treatment with demonstrated overall survival (OS) when the trials were designed.

Aim This global open-label expansion (OLE), single-arm REACH-2 cohort was initiated to study ramucirumab in patients with advanced HCC and baseline alpha fetoprotein (AFP) ≥400 ng/mL following a non-sorafenib based systemic therapy.

Methods Eligible patients have advanced HCC (BCLC stage C or B disease), Child-Pugh (CP) A, ECOG PS 0/1, baseline AFP ≥400 ng/mL, and 1-2 prior systemic regimens for HCC, excluding sorafenib or chemotherapy. Liver transplant patients are eligible. ~44 patients will receive ramucirumab 8mg/kg IV Q2W. Primary endpoint: safety; secondary endpoints include OS, progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes. Final analysis will occur after all patients have completed ≥3 cycles ramucirumab or discontinued.

Results As of interim data cutoff (31-January-2020), 24 patients were enrolled: 96 % male, median baseline AFP = 2094ng/mL (IQR:854, 7981), 50 % ECOG-PS 0, 96 % CP-A, 67 % ALBI grade1, and 92 % BCLC stage C. Most common prior systemic therapies were lenvatinib (n = 8), monotherapy PD-1/PD-L1 inhibitor (n = 9), PD-1 inhibitor+lenvatinib (n = 3), and atezolizumab+bevacizumab (n = 3). Grade≥3 TEAEs (≥10 %) were hypertension (n = 4), proteinuria (n = 3), and pneumonia (n = 3). No deaths due to AEs occurred. With median follow-up = 6.5 months, median PFS was 5.5 months (18 events; 95 %CI 1.3-7.5). ORR was 16.7 % (95 %CI 1.8-31.6). Median OS was immature (10 events).

Conclusions Safety and efficacy of ramucirumab following non-sorafenib-based systemic therapy was consistent with that observed in patients who received prior sorafenib in ITT REACH-2 population. Previously presented at ILCA 2020.

Publikationsverlauf

Artikel online veröffentlicht:
01. September 2021