Updated Efficacy and Safety Data from Imbrave050: Phase III Study of Adjuvant Atezolizumab (atezo) + Bevacizumab (bev) vs Active Surveillance in Patients (pts) with Resected or Ablated High-Risk Hepatocellular Carcinoma (HCC)

Background

At the pre-specified interim analysis (IA; median follow-up, 17.4 mo), IMbrave050 met its primary endpoint of improved independent review facility (IRF)-assessed recurrence-free survival (RFS) in pts with high-risk HCC. The RFS HR for atezo + bev vs active surveillance was 0.72 (adjusted 95% CI: 0.53, 0.98; P=0.012); overall survival (OS) was immature (HR, 1.42; 95% CI: 0.80, 2.54; Qin Lancet 2023)

Aim

This study report updated analyses.

Methods

IMbrave050 enrolled pts with HCC who had high recurrence risk (based on tumour size and number, vascular invasion and tumour differentiation) following curative-intent resection or ablation.

Pts were randomised 1:1 to receive atezo 1200 mg + bev 15 mg/kg IV every 3 weeks (17 cycles) or active surveillance for 1 y; pts were eligible to crossover to atezo + bev following IRF-recurrence.

Stratification factors included geographic region and a composite factor comprising the number of high-risk features, curative procedure and use of optional adjuvant transarterial chemoembolisation (1 cycle) post-resection.

Secondary endpoints included OS and safety

Results

• The updated RFS HR was 0.90 (95% CI: 0.72, 1.12). At the 2nd IA, OS remained immature (HR, 1.26; 95% CI: 0.85, 1.87). RFS and OS results were consistent across clinically relevant subgroups.
• No new safety concerns were observed.

	Atezo + bev (n=334)	Active surveillance (n=334)
RFS
Events, n (%)	162 (49)	164 (49)
RFS, median (95% CI), mo	33.2 (24.3, NE)	36.0 (22.7, NE)
Stratified HR (95% CI)	0.90 (0.72,1.12)
Stratified log-rank P value	NA; descriptive
OS
Events, n (%)	54 (16)	46 (14)
OS, median (95% CI), mo	NE (NE)	NE (NE)
Stratified HR (95% CI)	1.26 (0.85, 1.87)
Stratified P value	0.250

Clinical cutoff: 3 May 2024. Median follow-up: 35.1 mo.NA, not applicable; NE, not estimable

Conclusion

NIVO + IPI demonstrated statistically significant OS benefit vs LEN/SOR in pts with previously untreated uHCC, as well as higher ORR and durable responses with a manageable safety profile. These results support this combination as a potential new first-line SOC for uHCC.

Reference

Annals of Oncology (2024) 35 (suppl_2): 1-72. 10.1016/annonc/annonc1623

Transarterial Chemoembolization (TACE) With or Without Lenvatinib (len) + Pembrolizumab (pembro) for Intermediate-stage Hepatocellular Carcinoma (HCC): Phase III LEAP-012 Study

Background

TACE remains standard of care for intermediate-stage HCC

Aim

This study presents results from LEAP-012, a randomized, multicenter, double-blind, phase 3 trial evaluating len + pembro + TACE vs placebo + TACE in intermediate-stage HCC.

Methods

Eligible patients (pts) with HCC not amenable to curative treatment and Child-Pugh class A, no portal vein invasion, and ECOG PS of 0 or 1 were randomized 1:1 to len 12 mg (body weight ≥60 kg) or 8 mg (body weight <60 kg) QD PO + pembro 400 mg Q6W IV or to placebo PO + IV for up to 2 years; len/oral placebo alone continued until progression or discontinuation.

The first TACE occurred 2-4 weeks after the start of systemic therapy, with a maximum of 2 treatments per tumor (4 total), no more than once per month.

Randomization was stratified by study site, AFP, ECOG PS, ALBI grade, and tumor burden.

Primary end points were PFS per RECIST v1.1 by BICR and OS; HR and 95% CIs were estimated using a stratified Cox proportional hazards model with the Efron method of tie handling.

Results

• 480 pts were randomly assigned to len + pembro (n = 237) or placebo PO + IV (n = 243); both groups received TACE. At this first interim analysis, median time from randomization to data cutoff (Jan 30, 2024) was 25.6 months (range, 12.6-43.5).
• With 286 events, PFS was significantly improved for len + pembro vs placebo (HR, 0.66, 95% CI, 0.51-0.84; P = 0.0002; significance threshold, P = 0.025); median PFS was 14.6 months (95% CI, 12.6-16.7) vs 10.0 months (95% CI, 8.1-12.2).
• With 151 events (47.5%), OS was immature and the significance threshold was not met (HR, 0.80; 95% CI, 0.57-1.11; P = 0.0867; significance threshold, P = 0.0012).
• Grade 3-5 treatment-related adverse events (TRAEs) occurred in 71.3% of pts in the len + pembro group vs 31.5% in the placebo group; TRAEs led to the discontinuation of both study drugs in 8.4% vs 1.2% of pts, respectively.

Conclusion

LEAP-012 met its primary end point. Len + pembro + TACE showed a statistically significant, clinically meaningful improvement in PFS and an early trend toward improvement in OS vs placebo + TACE in pts with intermediate-stage HCC. The AE profile was consistent with known safety profiles of len, pembro, and TACE. OS will be retested in future analyses.

Reference

Annals of Oncology (2024) 35 (suppl_2): 1-72. 10.1016/annonc/annonc1623

Nivolumab (NIVO) plus Ipilimumab (IPI) vs Lenvatinib (LEN) or Sorafenib (SOR) as First-line (1L) Treatment for Unresectable Hepatocellular Carcinoma (uHCC): Expanded Analyses from CheckMate 9DW

Background

In the phase 3 CheckMate 9DW study, 1L NIVO + IPI demonstrated statistically significant and clinically meaningful overall survival (OS) benefit vs LEN/SOR in patients (pts) with uHCC (NCT04039607).

Aim

This study presents additional exploratory analyses from this preplanned interim analysis.

Method

Pts with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5 or 6, and ECOG performance status 0 or 1 were randomized 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles; then NIVO 480 mg Q4W) or LEN 8 mg or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity.

NIVO was given for a maximum of 2 years.

The primary endpoint was OS; secondary endpoints included objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1.

Results

• A total of 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333).
• At a median follow-up of 35.2 (range 26.8–48.9) months (mo), median OS was 23.7 (95% CI 18.8–29.4) mo with NIVO + IPI vs 20.6 (95% CI 17.5–22.5) mo with LEN/SOR (HR 0.79; 95% CI 0.65–0.96; P = 0.0180); 24-mo OS rates were 49% (95% CI 44–55) vs 39% (95% CI 34–45), respectively.
• OS benefit was generally consistent across pt subgroups.
• ORR was higher with NIVO + IPI vs LEN/SOR (36% [95% CI 31–42] vs 13% [95% CI 10–17]; P < 0.0001), with higher complete response rates (7% vs 2%) and durable responses (median DOR: 30.4 [95% CI 21.2–not estimable] vs 12.9 [95% CI 10.2–31.2] mo).
• Any-grade treatment-related adverse events (TRAEs) were reported in 84% of pts with NIVO + IPI vs 91% of pts with LEN/SOR; grade 3–4 TRAEs were reported in 41% vs 42% of pts, respectively.
• Additional exploratory efficacy and safety analyses will be presented.

Conclusion

In pts with previously untreated uHCC, NIVO + IPI demonstrated statistically significant OS benefit vs LEN/SOR, with higher ORR and durable responses, along with manageable safety. These results further support NIVO + IPI as a potential 1L treatment option for uHCC.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595

Five-year Overall Survival (OS) and OS by Tumour Response Measures from the Phase III HIMALAYA Study of Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma (uHCC).

Background

In the phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved OS vs sorafenib in the primary analysis (Abou-Alfa et al. NEJM Evid 2022) and demonstrated durable long-term survival with a 4-year OS rate of 25.2% (Sangro et al. Ann Oncol 2024).

Aim

This study reports the first 5-year OS analysis in uHCC and evaluate survival by multiple tumour response measures.

Method

Participants (pts) with uHCC were randomised to STRIDE, durvalumab monotherapy or sorafenib. OS, 5-year OS rates, OS by disease control (DC), changes in tumour size and depth of response (DpR; Osgood et al. J Clin Oncol 2019) and serious adverse events (SAEs) were assessed.

Extended long-term survivors were described. Data cut-off was 1 March 2024.

Results

• The OS hazard ratio (HR) for STRIDE vs sorafenib was 0.76 (95% confidence interval [CI], 0.65–0.89) (Table).
• The 5-year OS rate was 19.6% with STRIDE vs 9.4% with sorafenib (rate ratio, 2.09) and was further improved in pts who achieved DC (28.7% vs 12.7%; rate ratio, 2.26).
• OS rates for pts who achieved ≥G2 (>25%) tumour shrinkage were 58.0% (57 pts at risk) vs 36.0% (8 pts at risk) at 48 months and 50.7% (34 pts at risk) vs 26.3% (4 pts at risk) at 60 months for STRIDE vs sorafenib, respectively.
• The rate of treatment-related SAEs with STRIDE did not change from the primary analysis.

	STRIDE (n=393)	Durvalumab (n=389)	Sorafenib (n=389)
Median follow-up duration (95% CI), months	62.5 (59.5–64.8)	62.7 (60.8–63.8)	59.9 (58.3–61.5)
OS HR (95% CI)	0.76 (0.65–0.89)	0.85 (0.73–1.00)
OS rates (95% CI), %
48 months	25.2 (20.9–29.7)	19.0 (15.1–23.3)	15.1 (11.5–19.1)
60 months	19.6 (15.6–23.8)	14.4 (10.9–18.4)	9.4 (6.5–13.0)
OS rates in pts with DC (95% CI), %
48 months	36.3 (30.0–42.5)	28.9 (22.7–35.4)	20.2 (15.1–25.9)
60 months	28.7 (22.8–34.9)	21.8 (16.1–28.0)	12.7 (8.4–17.9)
Treatment-related SAEs, n/N (%)	68/388 (17.5)	33/388 (8.5)	37/374 (9.9)

 

Conclusion

STRIDE demonstrated an unprecedented 5-year survival rate, with no additional serious safety events in the extended follow-up. The improved OS outcomes observed across multiple tumour response evaluations, including DC and DpR, provide novel insights on the clinical benefit of dual immune checkpoint inhibition beyond conventional measures of response. These results set a new benchmark in uHCC, with one in five pts alive with STRIDE at 5 years.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595

Atezolizumab plus Bevacizumab or Lenvatinib versus Sorafenib as First-line Therapy for Advanced Hepatocellular Carcinoma: Overall Survival Using Real-world data from TrinetX Platform

Background

Atezolizumab plus bevacizumab (A+B) and lenvatinib (L) are approved first line systemic therapies for advanced hepatocellular carcinoma (HCC). They demonstrated superiority to sorafenib in clinical trials, but assessment from big real world data (RWD) studies are lacking.

Aim

This study presents results of overall survival (OS) using the TrinetX platform.

Method

Using TriNetX Global Collaborative Network we identified patients with advanced HCC from 66 healthcare organizations treated with S, L or A+B as first line systemic therapy.

Treatment start happend between January 2015 and December 2022.

Propensity score (PSM) was used to balance cohorts on age, gender and race.

Kaplan-Meier analysis was used to compare the 5-year overall survival (OS) between the cohorts.

Results

• We identified 7038 patients: 1030 treated with A+B, 1674 with L, and 4334 with S. Mean age was 65 years old and 78% were male.
• Second line therapy was received by 1682 patients (23.8%), 48% of them with immunotherapy.
• When analysing raw data, OS was significantly better with A+B (mOS 449 days) compared to S (mOS 374 days) (HR 0.88, 95% CI 0.80-0.97, p=0.047), and with L (mOS 460 days) compared to S (HR 0.90, 95% CI 0.84-0.98).
• After matching cohorts by sex, age, and race OS difference maintained with A+B vs S (HR 0.83, 95% CI 0.73-0.93, p=0.002) but it was not significant for L vs S (HR 0.92, 95% CI 0.84-1.01, p=0.12).

Conclusion

In this RWD setting, A+B maintains a robust OS benefit when compared to S as first line therapy for advanced HCC. L seems to be superior to S but difference in OS is not significant when patients data are matched. These results support the use of A+B as standard treatment.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595

Lenvatinib plus Drug-eluting Bead Transarterial Chemoembolization with or without hepatic arterial infusion chemotherapy for hepatocellular carcinoma (> 7 cm) with portal vein tumor thrombosis: A retrospective multicenter cohort study.

Background

The management of large hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains a great challenge. We aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC larger than 7.0 cm accompanied with PVTT.

Aim

This multicenter retrospective study evaluated consecutive patients with HCC (> 7.0 cm) and PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group)

Methods

Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score matching (PSM).

Results

• A total of 201 patients were included. After PSM, 83-paired patients remained in the study cohorts.
• Patients in the Len+DEB-TACE+HAIC group had higher ORR (66.3% vs. 38.6%, P < 0.001), longer TTP (median, 10.1 vs. 6.1 months, P < 0.001), and prolonged OS (median, 17.3 vs. 12.9 months, P < 0.001) than those in the Len+DEB-TACE group.
• The ORR and TTP of both intrahepatic tumor (ORR, 68.7% vs. 39.8%, P < 0.001; median TTP, 11.0 vs. 7.0 months, P < 0.001) and PVTT (ORR, 72.3% vs. 48.2%, P = 0.002; median TTP, 17.7 vs. 8.4 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group.
• The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.6% vs. 33.7%, P = 0.518).

Conclusion

The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with PVTT.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595

Efficacy and Safety of Lenvatinib vs Sorafenib in Hepatocellular Carcinoma: A Multi-center Real-world Study from the LINK Research Network

Background

• Recent studies have shown the non-inferiority of Lenvatinib (LEN) compared to Sorafenib (SOR) in survival outcomes in hepatocellular carcinoma (HCC), significantly influencing treatment strategies.

Aim

This study aimed to corroborate these findings by assessing the comparative efficacy and safety of LEN and SOR as first-line (1L) therapies by leveraging real-world data from South Korea.

Methods

Utilizing the LINK database, we identified HCC patients diagnosed from January 2015 to June 2022, treated with either 1L LEN or SOR.

Additional exclusions, beyond standard LINK criteria, included patients who had undergone liver transplant at any point or those who had received hepatectomy, loco-regional therapy, or radiation within 28 days prior to 1L.

We analyzed real-world overall survival (rwOS), time to first dose reduction, and adverse events (AEs) of interest such as such as hypertension, increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hand-foot syndrome (HFS), and proteinuria.

Incidence rates (IRs) per 1,000 person-years (PYs) were compared between the groups using propensity score matching to adjust for confounders, maintaining an alpha level of 0.05 for statistical significance.

Results

• Of 1,361 patients (1L LEN: 359, 1L SOR: 1,002), 1:1 PS-matching yielded 343 pairs with balanced covariates. 1L LEN showed a significantly longer median rwOS of 9.6 months (95% CI: 8.3-10.8) compared to 7.4 months (95% CI: 6.4-9.3) for 1L SOR (p=0.013).
• Time to first dose reduction was longer for 1L LEN (96.7 vs. 37.4 days, p<0.001) without significant difference in IRs (908.3 vs. 1072.6, p=0.252).
• Regarding AEs, 1L LEN had higher IRs of hypertension (204.5 vs. 129.7, p=0.046) and proteinuria (576.1 vs. 240.5, p<0.001), while 1L SOR had higher IRs of HFS (220.4 vs. 404.4, p=0.003), ALT increase (2,058.1 vs. 3,386.2, p<0.001), and AST increase (4,814.0 vs. 10,349.1, p<0.001).

Conclusion

The study confirms that 1L LEN offers survival benefits and a distinct safety profile compared to 1L SOR, as observed in clinical trials. Leveraging real-world data underscores its importance in validating long-term outcomes in clinical practice and supports therapeutic decisions for HCC.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595

- Lenvatinib versus Sorafenib as a Second-line Option in Patients with Unresectable Hepatocellular Carcinoma Previously Treated with Atezolizumab plus Bevacizumab: An Observational Study

Background

Atezolizumab plus bevacizumab (A+B) is a standard of care first-line (1L) systemic therapy for unresectable hepatocellular carcinoma (uHCC).

Aim

This study explores optimal sequencing of systemic therapy post A+B.

Methods

In this multicentre, retrospective study we examined efficacy and survival outcomes of patients (pts) with uHCC post A+B. Out of 935 pts treated with 1L A+B between May 2018 and August 2023, 454 discontinued 1L treatment and 214 started a second line (2L).

Overall, 151 pts were treated with sorafenib (SOR) or lenvatinib (LEN) and were included in the analysis and assessment for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR).

Results

• Of 151 eligible pts, 78 (51.7%) pts were treated with SOR while 73 (48.3%) were treated with LEN. There were no significant differences in gender, ECOG performance status, viral status, best response to 1L, and pattern of progressions (intra- vs extra hepatic progression) between the two cohorts.
• Median age was slightly higher in the LEN cohort compared to the SOR one (67.3 years vs 63.7 years, p=0.023). In the overall 2L study population, LEN exposure was associated with longer median PFS (3.09 versus 2.03 months, p=0.005) and OS (12.5 versus 7.83, p=0.044) compared to SOR.
• In 107 response-evaluable patients, LEN was associated with better ORR (8.8% vs 0%) and DCR (50% vs 28.8%) compared to SOR (p=0.001).
• A neutrophil-to-lymphocyte ratio (NLR) >5 assessed prior second line initiation, was associated with worse OS in multivariate analysis (HR 2.2, CI 95% 1.07-4.67, p 0.033).
• When considering OS from the time of A+B initiation, the A+B-LEN sequence was associated with better OS than A+B-SOR (21.4 vs 14.73 months, p=0.017).

Conclusion

Within the limitations of a non-randomised observational study, the A+B-LEN sequence was associated with better efficacy than A+B-SOR, highlighting the need of further investigations to choose the right TKI therapy post immunotherapy discontinuation.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595

Nivolumab (NIVO) plus Ipilimumab (IPI) vs Lenvatinib (LEN) or Sorafenib (SOR) as First-line (1L) Treatment for Unresectable Hepatocellular Carcinoma (uHCC): Expanded Analyses from CheckMate 9DW

Background

In the phase 3 CheckMate 9DW study, 1L NIVO + IPI demonstrated statistically significant and clinically meaningful overall survival (OS) benefit vs LEN/SOR in patients (pts) with uHCC (NCT04039607).

Aim

This study present additional exploratory analyses from this preplanned interim analysis.

Methods

Pts with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5 or 6, and ECOG performance status 0 or 1 were randomized 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles; then NIVO 480 mg Q4W) or LEN 8 mg or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity.

NIVO was given for a maximum of 2 years. The primary endpoint was OS; secondary endpoints included objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1.

Results

• A total of 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333).
• At a median follow-up of 35.2 (range 26.8–48.9) months (mo), median OS was 23.7 (95% CI 18.8–29.4) mo with NIVO + IPI vs 20.6 (95% CI 17.5–22.5) mo with LEN/SOR (HR 0.79; 95% CI 0.65–0.96; P = 0.0180); 24-mo OS rates were 49% (95% CI 44–55) vs 39% (95% CI 34–45), respectively.
• OS benefit was generally consistent across pt subgroups.
• ORR was higher with NIVO + IPI vs LEN/SOR (36% [95% CI 31–42] vs 13% [95% CI 10–17]; P < 0.0001), with higher complete response rates (7% vs 2%) and durable responses (median DOR: 30.4 [95% CI 21.2–not estimable] vs 12.9 [95% CI 10.2–31.2] mo).
• Any-grade treatment-related adverse events (TRAEs) were reported in 84% of pts with NIVO + IPI vs 91% of pts with LEN/SOR; grade 3–4 TRAEs were reported in 41% vs 42% of pts, respectively.
• Additional exploratory efficacy and safety analyses will be presented

Conclusion

In pts with previously untreated uHCC, NIVO + IPI demonstrated statistically significant OS benefit vs LEN/SOR, with higher ORR and durable responses, along with manageable safety. These results further support NIVO + IPI as a potential 1L treatment option for uHCC.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595

Lenvatinib (L) and Sorafenib (S) in Patients (pts) with Advanced or Unresectable Hepatocellular Carcinoma (uHCC): An International, Multicenter, Phase IV Study (STELLAR)

Background

L is a standard of care for pts with uHCC.

Aim:

This observational study characterized the hepatotoxicity/overall safety profile of first-line L in a real-world setting.

Methods

Study 508 is a prospective, nonrandomized, phase 4 study in Western pts (eg, Australia, Europe, and US) with uHCC treated with L or S via approved local prescribing practices.

No formal statistical comparisons were conducted. The primary endpoint was to further characterize hepatotoxicity/overall safety with L.

Medians for OS were estimated by the Kaplan-Meier method; 95% CIs were estimated via generalized Brookmeyer and Crowley method.

Results

• As of Oct 31, 2022, 242 pts were treated (L, n=149; S, n=93; Table). Median study follow-up was 9.5 mos with L and 7.4 mos with S.
• Hepatotoxicity TEAEs were reported in 23% of pts treated with L (most commonly hepatic encephalopathy, 7%) and 33% of pts treated with S (most commonly ascites, 12%).
• Overall, TEAEs were reported in 80% of pts treated with L and 82% with S. Grade ≥ 3/serious TEAEs were reported in 40%/30% of pts treated with L, and 38%/31% treated with S.
• The most common TEAE was decreased appetite (25%) for L; and diarrhea (28%) for S. Fatal TEAEs (most due to unknown causes or attributable to underlying disease) were reported for 9% of pts with L (1 TEAE [hepatic encephalopathy] was treatment-related) and 4% of pts with S; frequency may have been impacted by pt age and poor ECOG PS with L.
• Median duration of treatment (DoT) was 4.8 mos with L and 4.4 mos with S. After adjusting for DoT, rates of fatal TEAEs were 0.2 with L and 0.1 with S. Median OS (95% CI) was 16.3 mos (11.8–NE) with L and 13.6 mos (8.4–NE) with S

	L n=149	S n=93
Age: median, y (min, max)	69 (28, 88)	68 (28, 88)
≥75 y, %	29	23
ECOG performance status, %
0	44	48
1	29	27
2	8.1	4.3
3	0	2.2
Missing	19	18
Child-Pugh, %
Score 5/6	44/13	32/23
Grade A/B/C	58/13/1	55/16/1
Unknown/missing	18/9	26/2
Barcelona clinic liver cancer stage, %
0/A/B	3/10/25	0 /13/22
C/D/unknown/missing	29/2/26/5	28/3/31/3
Extrahepatic spread, %	33	33
Comorbidities, %
Alcoholic liver disease	30	41
Hepatitis C	34	31
Nonalcoholic fatty liver disease	3.4	6.5
Nonalcoholic steatohepatitis	4.7	5.4

 

Conclusions

The incidence/severity of hepatoxicity/overall safety in this study were consistent with the known safety profile of first-line L in pts with uHCC. OS was consistent with results from the REFLECT study. Findings support the positive benefit-risk profile of L in first-line treatment of pts with uHCC.

Reference

Annals of Oncology (2024) 35 (suppl_2): S656-S673. 10.1016/annonc/annonc1595