978P - Post-progression outcomes of advanced HCC patients (aHCC pts) treated with first-line atezolizumab/bevacizumab (A/B)

Background

The optimal treatment (Tx) strategy for aHCC pts who have progressed on frontline A/B is undefined. We evaluated 2nd line Tx patterns and clinical outcomes of aHCC pts following progression on A/B to identify factors associated with post-progression survival (PPS).

Methods

Real world patient data were retrieved from an international HCC database. PPS was from first radiographic progression on A/B to death. Kaplan-Meier median survivals and 95%CI were compared with univariate Cox-regression analysis. Univariate (UVA) and multivariate (MVA) Cox-regression analyses assessed the impact of baseline clinical factors on PPS.

Results

We identified 406 pts alive with progression on A/B. 220 continued active systemic Tx: 203 received 1 further line, 155 with tyrosine kinase inhibitors (TKIs), 45 with immunotherapy, and the remainder had missing data. Median duration of 2^nd line Tx was 2.2 months (mo) (IO: 2.3 mo, TKI; 2.1). Compared to pts who received best supportive care (BSC; n=186), pts on active Tx were younger, Child Pugh class (CP) A , ECOG <2 when A/B stopped, had viral etiology, no extrahepatic disease, and had disease control during A/B. Median follow-up from A/B progression was 7.5 mo (95%CI 6.3-8.6). mPPS for all pts was 6.0 mo (95%CI 5.2-7.2). Continued active Tx was associated with prolonged mPPS compared to BSC (9.7 vs 2.0 mo; HR: 0.30; 95%CI 0.2-0.4, p<0.001). mPPS was longer with IO (11.8 mo; 95%C: 6.4-NA) than with TKIs (8.1 mo; 95%CI 6.3-10.4) or BSC (2.0 mos ;95%CI 1.5-2.9). Male sex, ECOG ≥2 at time of A/B interruption, CP B/C, portal vein tumor thrombosis (PVTT), and primary progression on A/B were associated with increased risk of death in UVA. In MVA, PVTT, ECOG ≥2 and BSC independently predicted poor PPS. Active tx was associated with longer mPPS (8.6 mo, 95%CI 6.3-13.0 vs 2.5, 95%CI 2.1-4.4; HR:0.40, 95%CI 0.28-0.58) after performing propensity score matching for confounding factors (ECOG at A/B stop, PVTT, CPS, DCR during A/B).

Conclusions

In addition to known disease related factors, continuation of systemic Tx instead of BSC following progression on A/B is independently associated with improved PPS in pts with aHCC. mPPS was nearly 1 year with IO-based Tx, suggesting a potential role for IO beyond progression after A/B.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AstraZeneca, Basilea, Bayer, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Incyte, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche; Financial Interests, Institutional, Coordinating PI, National (Italian) coordinating PI: AstraZeneca, BeiGene; Financial Interests, Institutional, Local PI: Agios, Eisai, Fibrogen, Lilly, MSD, Zymeworks; Financial Interests, Institutional, Funding: Ipsen. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Böhringer Mannheim, EISAI, Incyte, Ipsen, Janssen, MSD, PierreFabre, Roche, Servier, Sirtex, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Incyte, Ipsen, Lilly, MSD, Roche; Financial Interests, Personal, Steering Committee Member: Roche, MSD, BeiGene, Jiangsu Hengrui Medicines.. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, MSD; Financial Interests, Institutional, Research Grant: Otsuka, Sumitomo Dainippon Pharma, EA Pharma, Taiho, Eisai, AbbVie, Gilead Sciences, Takeda, GE Healthcare, Chugai. S. Ulahannan: Financial Interests, Personal, Advisory Board: array, incyte, bayer, syros, eisai, AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, adlai nortye, arqule, atreca, BI, BMS, Celgene, Ciclomed LLC, Erasca, Evelo Biosciences, Exelexis, G1 Therapeutics, GSK, IGM biosciences, Incyte, isofol, Klus pharma, Macrogenics, merck, Mersana, Oncomed, Pfizer, regeneron, Revolution Medicines, Synermore Biologics, Takeda, Tarveda Therapeutics, Tesaro, Tempest, Vigeo, Tvardi, hutch med. D.J. Pinato: Financial Interests, Personal, Advisory Board: Mina Therapeutics, EISAI, Exact Sciences, MURSLA, H3B, DaVolterra, AstraZeneca, Bayer Healthcare; Financial Interests, Personal, Invited Speaker: BMS, IPSEN, Roche; Financial Interests, Personal, Other, Editor in Chief role: Wiley; Financial Interests, Institutional, Research Grant: BMS, MSD; Non-Financial Interests, Principal Investigator: Incyte, H3B, Starpharma, Roche, Ribon Therapeutics, Turning Point Therapeutics, Apollomics; Non-Financial Interests, Other, Charity Trustee: Cancer Treatment and Research Trust. All other authors have declared no conflicts of interest.