979P - Safety interim analyses of first-line systemic therapy with atezolizumab plus bevacizumab (ATZ+BEV) in patients from Spain with unresectable hepatocellular carcinoma (HCC): Phase IIIb ATHECA

Background

HCC progression is associated with an immunosuppressive tumour microenvironment enhanced by vascular endothelial growth factor (VEGF). ATZ+BEV, synergistically targeting programmed death ligand 1 (PD-L1) and VEGF, was approved as first-line systemic treatment for unresectable HCC after showing efficacy and acceptable safety profile in the pivotal IMbrave150.

Methods

This study evaluates safety and efficacy of 3-week intravenous cycles of first-line ATZ+BEV (1200 mg+15 mg/kg) in patients (pts) with unresectable HCC not previously treated with systemic therapy and with preserved liver function (Child-Pugh A). Here are presented safety interim results of the incidence and severity of treatment emergent adverse events (TEAE) grade (G) ≥3 leading to ATZ and/or BEV treatment discontinuation (primary objective) and other safety endpoints (secondary objectives).

Results

In 26 Spanish centres, 100 eligible pts (86 males, median age 66 years), received ATZ+BEV. At a median follow-up of 11.4 months, 63 pts had discontinued either BEV (63 pts) or ATZ (58 pts). TEAE G3 were reported in 44% pts, TEAE G4 in 1%, TEAE leading to death in 5% pts and serious TEAE in 32% pts. Treatment-related adverse events (TRAE) G3 occurred in 26% pts, mainly high levels of bilirubin and liver/pancreatic enzymes (9% pts), gastrointestinal-haemorrhagic disorders (4% pts) and arterial hypertension (7% pts). TRAE G4 was oesophageal varices haemorrhage in 1% pts. Serious TRAE occurred in 10% pts and immune-mediated TRAE G3 in 3% pts. TEAE leading to treatment discontinuation (G3: 9 pts; G4: none) were mainly gastrointestinal-haemorrhagic (4%) and liver biochemistry (2%) disorders. The 6 TEAE leading to death were hepatitis (the only TRAE), abdominal sepsis, aspiration pneumonia, haemoperitoneum, jaundice and hepatic encephalopathy (these last two events occurred in the same patient).

Conclusions

ATHECA preliminary safety data of first-line ATZ+BEV for unresectable HCC showed a TEAE profile similar to previous studies and consistent with the underlying disease and known safety profile of each agent.

Clinical trial identification

EudraCT 2020-005268-71, NCT04732286.

Editorial acknowledgement

Medical writing services were provided by María Dolores Julián from Linical and supported by Roche Farma S.A.

Legal entity responsible for the study

Roche Farma S.A.

Funding

Roche Farma S.A.

Disclosure

M.E. Reig Monzon: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, BMS, Eli-Lilly, Geneos, Ipsen, Merck, Roche, Universal DX; Financial Interests, Institutional, Research Funding: Carlos III Health Institute (ISCIII), Center for Biomedical Research Network (CIBER); Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, BMS, Eli-Lilly, Gilead, Roche; Financial Interests, Institutional, Research Grant: Bayer, Ipsen; Financial Interests, Institutional, Other, Educational Support: Bayer, AstraZeneca, Eisai-MSD, Roche, Ipsen, Lilly, Terumo, Next, Boston Scientific, Ciscar Medical. N. Luque Caro: Non-Financial Interests, Institutional, Principal Investigator: Roche Farma S.A.. J. Bruix: Non-Financial Interests, Personal, Advisory Board: Arqule, Bayer-Shering Pharma, Novartis, BMS, BTG-Biocompatibles, Eisai, Kiowa, Terumo, Gilead, Bio-Alliance, Roche, AbbVie, MSD, Sirtex, Ipsen, Astra-MedImmune, Incyte, Quirem, Adaptimmune, Lilly, Basilea, Nerviano, Sanofi; Non-Financial Interests, Personal, Invited Speaker: Bayer-Shering Pharma, Roche, BTG-Biocompatibles, Eisai, Terumo, Sirtex, Ipsen; Non-Financial Interests, Personal, Principal Investigator: Bayer, BTG, AbbVie, Roche, Arquile. C. Gomez Martin: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Bristol Myers Squibb, Eli-Lilly; Financial Interests, Personal, Invited Speaker: Eli-Lilly. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex, Terumo, Bayer, Adaptimmune; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, Incyte, AstraZeneca, Astellas Pharma; Financial Interests, Institutional, Research Grant: BMS, Sirtex; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal, Steering Committee Member: BMS, Boston Scientific, Roche. J. Sastre Varela: Financial Interests, Personal, Invited Speaker: Merck, Roche, Ipsen, Lilly, Pfizer, Servier, MSD; Financial Interests, Personal, Advisory Role: Roche, Amgen, Merck, Bayer, Celgene, Servier, BMS, Sanofi, Ipsen, Astellas, AstraZeneca; Financial Interests, Personal, Other, Travelling and accommodation support: Merck. J.M. Ordoñez Tres: Financial Interests, Personal, Full or part-time Employment: Roche Farma S.A.; Financial Interests, Personal, Stocks/Shares: Roche. J. Argemi: Financial Interests, Personal, Advisory Board: Roche Farma S.A.; Financial Interests, Personal, Invited Speaker: Roche Argentina, Pfizer. R. Perez Lopez: Financial Interests, Personal, Full or part-time Employment, VHIO staff (team leader of the Radiomics Group): VHIO; Financial Interests, Institutional, Research Grant, Co-PI of 3 research studies.: AstraZeneca; Financial Interests, Institutional, Research Grant, PI of a research study.: Roche. M.P. Torres Candela: Financial Interests, Personal, Full or part-time Employment: Roche Farma S.A.. J.L. Lledó-Navarro: Other, Personal, Advisory Board: Bayer, Roche, MSD, Eisai; Other, Personal, Invited Speaker: Bayer, Roche, MSD, Eisai. A.M. Matilla Peña: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai-MSD, Roche Farma S.A.; Non-Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai-MSD, Roche Farma S.A.. J. Montero: Financial Interests, Personal, Advisory Board: Roche, MSD; Financial Interests, Personal, Invited Speaker: Roche, MSD, Advanz, AbbVie. R.A. Pazo Cid: Financial Interests, Personal, Expert Testimony: AstraZeneca, Lilly; Financial Interests, Personal, Advisory Board: BMS, Ipsen, Roche, Servier; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Roche, Servier; Financial Interests, Institutional, Funding, Manuscript (medical writing and submission costs): Astellas, Ipsen; Financial Interests, Personal, Local PI: Astellas, Ipsen. M. Varela: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Eisai-MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Eisai-MSD.