Abstract
e16131 Background: There are no approved peri-operative anti‐cancer therapies for patients with hepatocellular cancer (HCC) who are candidates for liver resection (LR). Combination immunotherapy induces radiologically measurable responses in > 25% of patients with HCC, providing a rationale for neoadjuvant use in surgical candidates. Methods: PRIME‐HCC is a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab (3 mg/kg, day 1 and day 22) plus ipilimumab (1mg/kg, day 1 only) combination prior to LR in early-stage HCC. The primary objective of the study is to determine the treatment-related adverse events (trAE) and delays to surgery. Efficacy endpoints include overall response rates (ORR) by RECIST v1.1 and pathologic responses on resection specimens. Results: At the data censoring time of Jan 29th 2021, 7 patients were enrolled, all were of Child-Pugh class A, with cirrhosis (n = 6, 85.7%) secondary to viral etiology (n = 4, 57.2%). Male/female ratio was 6/1 and median age was 66 (range: 57-70). The median diameter of the dominant liver lesion was 3.3 cm (inter quartile range, IQR 1.2, range 1.1-4.1 cm) and the median number of nodules was 2 (IQR 0.5; range 1-3). Study part I (n = 6) was completed with no surgical delays. TrAEs of all grade were observed in 6/7 safety-evaluable patients (85%). TrAEs of grade >2 occurred in 3 patients (42%) and included grade 3 transaminitis (n = 1), grade 2 thyroid toxicity (n = 1), grade 2 infusion reaction (n = 1) and fatigue (n = 1). One patient was diagnosed with cholangiocarcinoma after dosing and was removed from efficacy analyses. ORR according to RECIST v1.1 criteria in efficacy-evaluable patients (n = 5) was 20%, including 1 partial response and 4 disease stabilisations. Pathological responses were observed in 3 out of 5 pathologically evaluable patients (60%). Conclusions: Neoadjuvant immunotherapy with nivolumab plus ipilimumab is tolerable, does not compromise management of patients on a radical pathway of care and is characterised by anti-tumour efficacy in early-stage HCC. Clinical trial information: NCT03682276.
Highlights
After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence
In Non-small cell lung cancer (NSCLC), neoadjuvant checkpoint blockade leads to a higher proportion of major pathologic responses compared to chemotherapy
[25] and the phase II NEOSTAR trial, has shown that treatment with nivolumab/ipilimumab leads to higher major pathological responses (33%) compared to nivolumab (17%) [26]
Summary
After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. In patients within the Barcelona Clinic Liver Cancer (BCLC) stage 0 or A criteria, surgical resection can be carried out safely with curative intent [3]. This is only feasible in < 30% of the patients, mainly due to the extent of radiological spread of the disease or poor synthetic function due to underlying cirrhosis. Pembrolizumab has shown initial evidence of disease-modulating activity in a little less than 20% of patients enrolled in Keynote-224 [4], but failed to improve OS in Keynote240, a placebo-controlled phase III trial which investigated pembrolizumab in treatment-experienced patients with advanced HCC [5].
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