Use of IO-Based Therapy Associated With Real-World OS Benefit in HCC

The use of an immuno-oncology (IO) regimen as systemic therapy was found to be an independent prognostic factor and was associated with improved long-term survival for patients with hepatocellular carcinoma (HCC), regardless of IO’s sequencing in the first and later lines of treatment, according to findings from a retrospective, real-world analysis.¹

Findings presented at the 2023 International Liver Cancer Association Conference revealed that in a multivariable Cox regression analysis of the whole cohort, IO use emerged as an independent prognostic factor for survival (HR, 0.645; 95% CI, 0.496-0.830; P = 0.001).

Between 4 treatment sequencing strategies evaluated, there was no significant difference in median overall survival (OS; log-rank P = .475). Patients treated with a multikinase inhibitor (MKI) followed by MKI (n = 37) experienced a median OS of 15.9 months (95% CO, 12.0-19.9). Those given MKI followed by IO (n = 79) had a median OS of 14.8 months (95% CI, 10.2-19.3). Patients treated with IO followed by MKI (n = 41) achieved a median OS of 24.4 months (95% CI, 18.5-30.3). Those who received IO followed by IO (n = 15) had a median OS of 22.5 months (95% CI, 19.1-25.8).

Median OS favored patients treated with first-line IO (n = 56) vs first-line MKI (n = 116) at 24.1 months (95% CI, 21.0-27.3) vs 15.3 months (95% CI, 12.9-17.7), respectively. However, this difference did not achieve statistical significance (HR, 0.766; 95% CI, 0.527-1.114; P = .162). Similarly, 12- and 24-month (OS24) survival rates favored first-line IO over MKI at 75% (95% CI, 63.6%-86.4%) and 52.6% (95% CI, 39.3%-65.9%) with first-line IO, respectively, vs 58.3% (95% CI, 49.3%-67.3%) and 27.8% (95% CI, 19.4%-36.2%) with MKI, respectively.

Notably, within the first-line MKI group, those who received subsequent IO demonstrated a superior OS24 (31.3% vs. 14.3%). Furthermore, patients who received a sequence of 2 MKIs and subsequently received IO (n = 8) exhibited a prolonged median OS of 35.8 months compared with a median OS of 14.1 months in those who did not (n = 29; HR, 0.247; 95% CI, 0.082-0.745; P = 0.008).

“Given the lower proportion of [patients treated with] first-line MKIs receiving subsequent treatment, and lower OS24 in first-line MKI sequences, our findings suggest first-line IO to be the preferred approach,” lead study author Kevin Mok, MD, of Prince of Wales Hospital, Hong Kong, and colleagues wrote in a poster presentation of the data. “For patients treated with first-line MKI, IO should be used subsequently.”

Regarding the timing of IO use, no significant difference in median OS was observed between first-line IO (18.2 months) and IO administered in the second line or beyond within the overall cohort (15.9 months; P = 0.515). The median OS from the initiation of second-line treatment was 8.4 months with IO and 8.0 months with MKI (HR, 0.850; P = 0.293). Notably, OS24 favored second-line IO use, with this approach producing an OS24 rate of 26.9% vs 20.3% with MKI.

This analysis aimed to assess the outcomes of different treatment sequences involving IO and MKI/anti-VEGFR agents to evaluate the ideal timing for IO in the treatment course for patients with HCC. This study included patients who were diagnosed with HCC between January 2008 and December 2021 and had attended Prince of Wales Hospital.

To be included in the analysis, patients were required to have undergone 2 or more lines of systemic treatment. Acceptable first-line MKIs consisted of sorafenib (Nexavar) or lenvatinib (Lenvima); in the second-line, patients could receive sorafenib, lenvatinib, ramucirumab (Cyramza), regorafenib (Stivarga), or cabozantinib (Cabometyx)

The study's primary end points were median OS and OS24. Baseline characteristics of various treatment groups were statistically compared, employing the chi-square test, Fisher's exact test, or T-test, as appropriate. OS was assessed using the Kaplan-Meier method and analyzed with the log-rank test. Hazard ratios were calculated for prognostic factors and survival through Cox regression analysis.

The study enrolled a total of 741 patients diagnosed with HCC, 533 of whom received the MKI regimen and 108 of whom received IO therapy. Subsequent systemic therapy was administered to 150 patients in the MKI group vs 56 in the IO group.

Among the patients who received first-line MKI, 37 (31.9%) went on to receive second-line MKI and 79 (68.1%) received second-line IO. Of those in the first-line IO group, 41 (73.2%) received MKI and 15 (26.8%) received IO as their next line of therapy.

Sixty-eight patients (58.6%) were 60 years of age or older among those first given MKI (group A) compared with 37 (66.1%) in those first treated with IO therapy (group B). HbsAg positivity occurred in 89 patients (76.7%) in group A and 44 patients (78.6%) in group B. A smaller subset tested positive for anti-HCV, accounting for 9 (7.8%) and 3 cases (5.4%), respectively, although data were missing for some individuals in both groups. An ECOG performance status of 0 and 1 was observed in 78 patients (67.2%) and 26 patients (46.4%), respectively.

In group A, alcohol use, hypertension, and diabetes mellitus were observed in 46 patients (39.7%), 40 patients (34.5%), and 24 patients (20.7%). These numbers were 21 (37.5%), 21 (37.5%) and 10 (17.9%), respectively, in group B.

The majority of patients in both groups fell into the advanced stages of Barcelona Clinic Liver Cancer (BCLC) staging scale, comprising 106 patients (91.4%) in group A and 44 patients (78.6%) in group B. Tumor macrovascular involvement was observed in 45 patients (38.8%) and 17 patients (30.4%), respectively, and extrahepatic involvement was recorded in 72 patients (62.1%) and 30 patients (53.6%), respectively. The number of liver nodules varied; no liver nodules were seen in 14 patients (12.1%) in group A and 5 patients (8.9%) in group B, whereas 82 patients (70.7%) and 41 patients (73.2%), respectively, had multiple liver nodules. The largest tumor size was greater than 5 cm in approximately half of the patients in both groups.

Regarding treatment history, 65 patients (56.0%) and 41 patients (73.2%) in these respective groups had prior locoregional treatment or surgery, and 13 patients (11.2%) and 9 patients (16.1%) had locoregional treatment or surgery during or after systemic treatment initiation. Notably, the majority of patients in both groups initiated their first systemic treatment after 2017, at 104 patients (89.7%) and 54 patients (96.4%), respectively. IO use was reported in 87 patients (75.0%) in group A and all 56 patients in group B.

Reference

Mok K, Yip T, Mo F, et al. A study on the sequence of systemic treatment in hepatocellular carcinoma. Presented at: 2023 International Liver Cancer Association Conference; September 7-9, 2023; Amsterdam, Netherlands. Abstract P-98.