Advancements in Hepatocellular Carcinoma Treatment: Insights from ASCO 2024

Non-Sponsored Content

ONCOLOGY

Medical writer: Audrey TANG | Last updated: 12 August 2024 | In: Therapeutic Areas, Oncology

Article Keywords

neoadjuvant immunotherapy, major pathological response, FGFR2 fusion/rearrangement inhibitor, combination immunotherapy regimens, cholangiocarcinoma, hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a devastating disease with limited treatment options. Recent trials presented by ASCO 2024 spotlight new findings on neoadjuvant immunotherapy, combination regimens for HCC, and efficacy of novel monotherapies.

MPR as Surrogate Endpoint for RFS in HCC Neoadjuvant Immunotherapy

A recent study analysed combined data from 86 HCC patients from 4 prospective phase I/II trials and 23 patients off-trial who had received neoadjuvant immunotherapy.¹ In total 100 patients were found to be evaluable for a pathological response, of which 33% achieved a major pathological response (MPR) and 19% a pathological complete response (pCR).¹ Achieving an MPR was significantly associated with improved relapse-free survival (RFS), with the median RFS not being reached in patients who achieved MPR compared to 28.3 months for those who did not (HR, 0.27; 95% CI, 0.11–0.69, p=0.003).¹ Similarly, pCR was also associated with improved RFS, with median RFS not reached compared to 32.8 months (HR, 0.20; 95% CI, 0.05–0.82; p=0.013).¹ The study highlights that MPR may be a surrogate endpoint for RFS following neoadjuvant immunotherapy for HCC, warranting further clinical validation.¹

Achieving the Best Outcomes under COVID-19 Endemicity

Inactivated and mRNA COVID-19 vaccines in patients with autoimmune rheumatic diseases – A city of two tales

Late but sinister post-COVID-19 conditions: new-onset rheumatic diseases

COVID-19 Infection and Subfertility: A Subtle and Debatable Complication

Previous Next

17 May 2023

Achieving the Best Outcomes under COVID-19 Endemicity

30 January 2023

Inactivated and mRNA COVID-19 vaccines in patients with autoimmune rheumatic diseases – A city of two tales

Phase 3 Studies Investigate the Efficacy and Safety of Combination Immunotherapy Regimens Compared to Single-Agent Therapies in Patients with Advanced HCC

First-line (1L) therapies based on PD-L1 inhibitors are standard of care in advanced HCC (aHCC). However, prognosis remains poor and there is an unmet need for alternative therapies with long-term benefits. Two studies compare different immunotherapy treatment combinations for aHCC.

The LEAP-002 trial (NCT03713593) evaluated the efficacy and safety of 1L lenvatinib (LEN) plus pembrolizumab (PEMBRO) vs LEN plus placebo (PBO) in patients with aHCC.² The study did not meet its primary endpoints of overall survival (OS) and progression-free survival (PFS), despite showing activity in the combination treatment arm.² With additional follow-up, the median OS was 21.1 months for LEN + PEMBRO vs 19.0 months for LEN + PBO (HR, 0.840; 95% CI, 0.708–0.997). The median PFS was 8.2 months vs 8.1 months (HR, 0.810; 95% CI, 0.692–0.949), respectively. Finally, the overall response rate (ORR) was also higher with LEN + PEMBRO vs LEN + PBO (26.3% vs 17.5%).²

The CheckMate 9DW trial (NCT04039607) compared nivolumab (NIVO) plus ipilimumab (IPI) (n=335) to LEN or sorafenib (SOR) (n=333) as a 1L treatment option for unresectable HCC.³ In the comparator arm, 85% (n=275) was treated with LEN. The study found that NIVO + IPI demonstrated a statistically significant OS benefit compared to LEN or SOR, with a median OS of 23.7 months vs 20.6 months (HR, 0.79; 95% CI, 0.65–0.96; 2-sided p=0.0180).³ Additionally, the combination showed higher ORR by RECIST v1.1 (36% vs 13%) and longer duration of responses (30.4 months vs 12.9 months) when compared to LEN or SOR.³

These studies highlight the ongoing efforts to improve and expand treatment options for HCC patients, with results suggesting that neoadjuvant immunotherapy and combination regimens may offer improved survival outcomes.

Tinengotinib Shows Promise in Advanced Cholangiocarcinoma

Another study (NCT04919642) evaluated the efficacy and safety of tinengotinib, an FGFR2 fusion/rearrangement inhibitor, as monotherapy in patients with advanced, metastatic cholangiocarcinoma (CCA).⁴ The trial included four cohorts: those with FGFR2 fusion(s) who had progressed on prior FGFR inhibitor (FGFRi), those with acquired resistance to a prior FGFRi, those with non-fusion FGFR alterations, and those with wild-type FGFR.⁴ The primary endpoint was the ORR per RECIST v1.1.⁴ Results showed that tinengotinib had promising clinical benefit for patients with FGFR2-fusion CCA after prior FGFRi, as well as for those with non-fusion FGFR alterations with a manageable toxicity profile.⁴

References

D’Alessio A, et al. J Clin Oncol. 2024;42(3_suppl):506.

Finn RS, et al. J Clin Oncol. 2024;42(3_suppl):482.

Galle PR, et al. J Clin Oncol. 2024;42(3_suppl):LBA4008.

Javle MM, et al. J Clin Oncol. 2024;42(3_suppl):434.

Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).