Session II: Hepatocellular Cancer
SESSION II WEBCAST (with Slides - needs a registration)
Late-Breaking Abstract-3: CheckMate 459: long-term efficacy outcomes with nivolumab versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma
The authors conclude that at a minimum follow-up of 33.6 months, NIVO continued to demonstrate a clinically meaningful benefit as 1st-line therapy in advanced HCC (median OS was 16.4 months for NIVO & 14.8 months for SOR <p=0.0522>; the 33-month OS rate was 29% for NIVO & 21% for SOR; consistent OS benefit with NIVO was observed regardless of PD-L1 status or viral etiology.
According to the conclusions, NIVO continued to demonstrate a more favorable safety profile than SOR (fewer grade 3-4 TRAEs and TRAEs leading to discontinuation; no new unexpected safety signals; liver function was preserved over time in the NIVO arm compared with SOR).
Short Oral-6: The influence of liver function on the outcomes of phase II trial of sorafenib vs. hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma
The authors conclude that in pts with mALBI grade of 1-2a, OS was not different between SOR & HAIC arm (15.2 months vs. 18.3 months in SOR & HAIC arm). OS was better in the SOR arm than in the HAIC arm in pts with mALBI grade of 2b, because of low induction rate of 2nd-line treatment due to liver function in such pts (15.1 months vs. 7.4 months in SOR & HAIC arm).
The authors conclude that SOR will precede HAIC for pts with aHCC, especially those with mALBI grade of 2b because they will be ineligible for SOR after failure to HAIC.
Short Oral-7: Efficacy and safety of transarterial chemoembolization (TACE) plus apatinib as compared with TACE alone for recurrent hepatocellular carcinoma: a prospective randomized controlled trial
The authors conclude that TACE plus apatinib treatment is safe for patients with recurrent HCC, AEs with apatinib need to be monitored during the application, despite the manageable appearance. TACE plus apatinib might be of potential benefit to pts with recurrent HCC. Further large sample RCTs are needed to better define the relative benefits of apatinib in recurrent HCC.
Short Oral-8: Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled Analyses
The authors conclude that the sustained release of anthracyclines and durable embolization from LifePearl® microsphere makes LifePearl® TACE an efficient and safe treatment option for pts with an early and intermediate stage HCC. The data from 586 pts treated for unresectable HCC with LifePearl® microspheres loaded with doxorubicin or idarubicin showed 57% of treated pts in BCLCC =/A stage clearly demonstrates treatment stage migration in a real live with good tolerance & acceptable toxicity. A high tumor response rate was observed that translated into promising PFS, TTUP & OS. The OS in this analysis is similar to the best OS observed in recent TACE trials. Hepatotoxicities as imaging findings were lower than with older DEM-TACE and similar to cTACE studies.
Short Oral-9: Outcomes for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh B liver function in the phase 3 CELESTIAL study of cabozantinib vs placebo
The authors conclude that in this retrospective explorative analysis of pts whose liver function deteriorated to Child-Pugh B by week 8 cabozantinib appears to have a manageable safety profile in this group of pts with comparable dose reduction and discontinuation rates to the overall population. HR for OS & PFS suggests the presence of clinical benefit in this subgroup. Further studies are warranted in Child-Pugh B pts with HCC, a population with considerable unmet need.
Oral-5: Efficacy and safety of nivolumab + ipilimumab in Asian patients with advanced hepatocellular carcinoma: subanalysis of the CheckMate 040 study
The authors conclude that in the NIVO+IPI combination cohort clinicaly meaningful responses were observed overall and in the Asian subpopulation: The mOS was longest in Arm A (NIVO + IPI3) in both the Asian subpopulation and the overall population; DCR was highest and progressive disease rate lowest in Arm A in both the Asian subpopulation and the overall population; small differences between the two populations may be related to the small sample size or variation in baseline etiology.
The safety profiles for the NIVO+IPI combinations were similar between the Asian subpopulation and the overall population. Reported AEs were manageable and no new safety signals were identified.
Oral-6: The Novel regimen of tremelimumab in combination with durvalumab provides a favorable safety profile and clinical activity for patients with advanced hepatocellular carcinoma (aHCC)
The authors conclude that all arms demonstrated an acceptable safety profile. No new safety signals were identified beyond the established profile for each agent, alone or in combination and only 24.3% pts receiving the T300+D regimen required steroids for treatment-related AEs.
A single priming dose of tremelimumab combines with monthly durvalumab (T300+D arm) showed promising clinical activity in the predominantly 2nd-line HCC population. The confirmed ORR per RECIST v1.1 in the T300+D arm was 24% & the median DOR has not yet been reached. Median OS (95% CI) was 18.7 (10.8-27.3) months in the T300+D arm.
Accross al arms, T300+D provides the best benefit-risk profile. The unique association of the T300+D regimen with proliferative CD8+ T-Cells provides a biologic rationale for the observed treatment response. T300+D and D are being evaluated vs sorafenib in the ongoing phase 3 HIMALAYA study (NCT03298451)
Oral-8: Atezolizumab + bevacizumab vs sorafenib for unresectable hepatocellular carcinoma (HCC): Results from older adults enrolled in IMbrave150
The authors conclude that similar to the IMbrave150 ITT population, older adults with previously untreated, unresectable HCC derived a clinically meaningful benefit from atezolizumab + bevacizumab vs sorafenib (OS, PFS & ORR benefit were consistent across ages; PRO benefit, including delayed deterioration in QOL, functioning and key disease-related symptoms, is consistent across ages).
The safety of atezolizumab + bevacizumab in older adults is generally consistent with that in younger pts, with no significant added risks or toxicities, despite higher rates of baseline comorbid medical conditions.
The authors conclude that atezolizumab + bevacizumab should be considered as a practice-changing treatment even amongst older adults with unresectable HCC who have not received prior systemic treatment.
Clinical Forum granted by Lilly:
Precision Medicine development in Gastro-Intestinal Oncology
Evidence-based Guidelines using Biomarkers in treatment decision making. Optimising management and sequencing.