INST OX‐05‐024: first line gemcitabine, oxaliplatin, and erlotinib for primary hepatocellular carcinoma and bile duct cancers: a multicenter Phase II trial

Abstract

Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease‐control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0.2 and 0.4, respectively) were set as undesirable (null) and desirable results. 26 HCC and 7 BDC patients were accrued. In HCC, 1 PR, 10 SD, and 9 PDs were seen. DCR in HCC was 42%. Among seven (7) patients with BDC, one patient was not evaluable; one achieved a long lasting PR, and five patients had SD and DCR was 86%. Median overall survival (OS) times and progression‐free survivals (PFS) were 196 and 149 days in HCC and 238 days and not reached in BDC. PFS at 26 weeks in HCC was 41% and at 21 weeks in BDC was 60%. Grade 3 toxicities in >5% of patients were fatigue (12.9%), neutropenia (9.6%), thrombocytopenia (9.6%), and diarrhea (6.4%). G+O+E exceeded both preset P0a and P1 of the primary objective with a PFS of 41% at 26 weeks for HCC and preliminary BDC data may warrant further investigations.

Mechanisms and therapeutic targets of ErbB family receptors in hepatocellular carcinoma: a narrative review

“…The results showed a median overall survival (OS) of 9.9 months, with a 16-week PFS rate of 43%, demonstrating encouraging efficacy outcomes. Patt et al .’s phase II clinical study ( 115 ) did not demonstrate a significant survival benefit among HCC patients receiving combination therapy of oxaliplatin, gemcitabine, and erlotinib. Recent results from a multicenter phase II clinical trial indicated that the combination of bevacizumab and erlotinib, compared to sorafenib alone, did not affect the OS of patients with advanced HCC, but the combination therapy resulted in a longer median event-free survival and demonstrated superior safety and tolerability profiles ( 116 ).…”