Low dose nivolumab with TKI in advanced HCC: Real world outcomes from India

Checkpoint Inhibitor with bevacizumab is unaffordable for most in India and other LMICs. Low dose nivolumab (LD Nivo) has shown comparable efficacy in other solid tumors such as HNSCC, RCC and NSCLC.

In this retrospective study we analyzed the efficacy and safety of LD Nivo+TKI in patients with advanced HCC not amenable for locoregional therapy. Details regarding stage at presentation, hepatic function, patterns of Nivolumab dosing, tolerability and survival outcomes were analyzed. We also report the subsequent lines of therapy post progression.

Between Aug 2019 – Aug 2022, 50 patients received LD Nivo+TKI with a mean age of 52.2 years, male (80%), ECOG 1(78%), BCLC C(78%), B(14%), A(6%)and D(2%). Majority were multifocal (66%) with a mean size of target lesion of 10.6 (IQR-7.2-13.1) cms. Most had CLD (76%), portal hypertension (56%) and esophageal varices (44%). CLD Etiology was Hepatitis B (40%), NAFLD (14%) and alcohol (8%). MVI/PVT was present in 54% of the patients and extrahepatic spread in 36% with 22% having both. Most were Child-Pugh class A (72%). The median AFP at diagnosis was 1036 (IQR–136.75-86462.5) ng/ml. The ALBI grade was 2(62%) > 1(32%) > 3(6%). 42% patients had received prior systemic therapy with TKIs for intermediate stage HCC. Two patients had undergone prior surgical resection and 4 patients had received TACE and RFA. TKIs used were Lenvatinib(76%) and Cabozantinib(10%). LD Nivo alone was used in 14%. The median dose of Nivolumab every 2 weeks was 30.82mg(IQR-26.66-66.66) and the median dose/kg/2-weeks was 0.57(IQR-0.45-1.11). 23 patients received < 2 doses of treatment. At a median follow up of 32.5 weeks, the median OS of the whole cohort and those who received ≥2 doses was 57 weeks (95% CI 33.46-80.53) and 74 weeks (95% CI-2.74–63.26) respectively. Median PFS of the whole cohort and those who received ≥2 doses was 42 weeks (95% CI 29.32-54.68) and 50 weeks (95% CI-33.71–66.28) respectively. At progression, only 26% of the patients had further systemic therapy – TKI alone (16%) and Nivo + next line TKI (6%). TRAEs occurred in 14(28%) of patients, the commonest being hypothyroidism 10(20%), HFS 5(10%) and hepatitis 4(8%). irAE’s were hepatitis, hypophysitis and primary hypothyroidism noted in one patient each. Treatment discontinuation due to SAE (hypophysitis) occurred in 1 patient. The cost of one cycle of treatment with LD Nivo (40mg) + TKI(Len/Cabo) was $732.18 compared to $3538.8 for one cycle of Atezolizumab + Bevacizumab.

Low dose nivolumab with TKI is active in patients with locally advanced inoperable HCC. Outcomes are improved as compared to historic cohort of first-line TKI alone in this disease with poor prognosis. Only a quarter of patients in the real world receive subsequent lines of treatment. Prospective trials to establish the role of low-dose immunotherapy + TKI in HCC are needed.

The authors.

Has not received any funding.

All authors have declared no conflicts of interest.