Background and Objective Hong Kong, like many parts of Asia, faces a high burden of hepatocellular carcinoma (HCC) caused by high endemic rates of hepatitis B virus infection. Hong Kong clinicians have developed a high level of expertise in HCC treatment across surgical, transarterial, ablative, radiotherapeutic and systemic modalities. This publication summarizes the latest evidence-based recommendations on how these modalities should be used. Methods In two meetings held in 2020, a multidisciplinary panel of surgeons, oncologists and interventional radiologists performed a narrative review of evidence on the management of HCC, with an emphasis on treatment of HCC not amenable to surgical resection. Close attention was paid to new evidence published since the previous version of these statements in 2018. Key Content and Findings The expert panel has formulated 60 consensus statements to guide the staging and treatment of unresectable HCC. Since the previous version of these statements, considerable additions have been made to the recommendations on use of targeted therapies and immunotherapies because of the large volume of new evidence. Conclusions Our consensus statements offer guidance on how to select HCC patients for surgical or non-surgical treatment and for choosing among non-surgical modalities for patients who are not candidates for resection. In particular, there is a need for more evidence to aid physicians in the selection of second-line systemic therapies, as currently most data are limited to patients with disease progression on first-line sorafenib.

Introduction: Human epidermal growth factor receptor 2 (HER2) amplification is commonly detected in breast cancer tissue samples by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) tests in clinical practice. It has been reported that cell-free DNA (cfDNA) may better capture the heterogeneity of acquired resistance than tumor biopsy. This study aims to develop a noninvasive digital polymerase chain reaction (PCR) assay for the detection of HER2 amplification in the plasma cfDNA of breast cancer patients. We further examine the concordance rate of HER2 amplification detected by blood-based digital PCR with tissue-based IHC/FISH tests. Materials and Methods: Plasma samples from 32 breast cancer patients were prospectively collected at Queen Elizabeth Hospital (Hong Kong SAR, China). According to previous IHC/FISH records, 15 patients were scored as HER2 amplified (IHC score 3 and/or FISH positive) and 17 patients as HER2 non-amplified. The detection of plasma cfDNA was performed by droplet digital PCR (ddPCR). The EFTUD2 gene was used as a reference and HER2:EFTUD2 ratio was assessed by ddPCR on the plasma DNA from cancer samples. Results: A median of 1.47 (range 0.92-3.83) was detected in the HER2 amplified patients and a median of 1.03 (range 0.76-1.23) was detected in the HER2 non-amplified patients by ddPCR. Our results showed that using 1.30 as the cutoff, ddPCR assay could well detect HER2 amplification. Receiver operating characteristic analysis was used to evaluate the diagnostic ability of this ddPCR assay and it returned an area under the curve of 0.898. A diagnostic test was used to evaluate the concordance of this ddPCR assay with the IHC/FISH tests and determine the sensitivity (73.33%), specificity (100%), accuracy (87.5%), positive predictive value (100%), and negative predictive value (81%) of the ddPCR assay. Conclusion: Accurate reporting of HER2 amplification status is a prerequisite for the appropriate choice of targeted therapy. We have obtained a high level of concordance in comparison to tissue-based IHC/FISH when cfDNA ddPCR assay was used to determine HER2 amplification in breast cancer patients. Most importantly, we have established a great accuracy of the ddPCR assay. Increasing studies have reported that HER2 levels may change during targeted therapy, but there are additional risks of patients by the invasive nature of IHC/FISH tests. Our results support the potential application of blood-based ddPCR assay to monitor the changes of HER2 amplification status in breast cancer patients during targeted therapy. Citation Format: William C. Cho, Eunice Y. Lau, Jeffrey C. Chan, Anna Y. Tai, Alex K. Leung, Anthony K. Leung, Michelle O. Szeto, Elizabeth Y. Chuk, Tony Y. Yuen, Molly W. Fung, Roger K. Ngan. Noninvasive detection of HER2 amplification in breast cancer with plasma DNA digital PCR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5155.

e16179 Background: Cabozantinib is licensed for use as second- or third-line treatment for sorafenib-exposed advanced hepatocellular carcinoma (aHCC) based on the phase III CELESTIAL trial. However, its use in the post-immune checkpoint inhibitors (ICI) setting has yet to be described. We evaluated the pattern of use, efficacy, survival and tolerability of cabozantinib in aHCC patients with previous treatment by ICIs. Methods: We did a multi-centre, territory-wide study analysing aHCC patients who received cabozantinib after prior ICIs. Objective response rate (ORR), disease control rate (DCR), time-to-progression (TTP), overall survival (OS) and treatment related adverse events (TRAEs) were assessed. Results: Thirty-one patients were included. The median age was 58.0 (range 41-85) and 77.4% had Child-Pugh A cirrhosis. 51.6% of patients received single agent cabozantinib and 48.4% received cabozantinib in combination with ICIs. ≥80% of patients received cabozantinib beyond the second-line and 93.5% of patients had prior TKIs. All patients received prior anti-PD-1 and 61.3% had prior anti-CTLA-4. The median follow-up was 15.2 months. For single agent cabozantinib patients, the ORR was 6.3%, DCR was 31.3% and median TTP was 3.5 months (95% C.I. 1.2-5.8). For cabozantinib-ICI combination patients, the ORR was 6.7%, DCR was 26.7% and median TTP was 2.3 months (95% C.I. 1.4-3.1). The overall median OS was 8.9 months (95% C.I. 5.7-11.9). Single agent cabozantinib patients had a significantly shorter OS compared to cabozantinib-ICI combination patients (8.3 months (95% C.I. 1.3-15.2) vs. 15.1 months (95% C.I. 11.1-19.2), p = 0.047). There was no significant difference in OS among patients with primary resistance to prior ICI regimes compared to those with acquired resistance (primary resistance 8.28 months (95% C.I. 5.04-11.5) vs. acquired resistance 8.90 months (95% C.I. 3.49-14.3), p = 0.472). Overall, 67.7% and 6.5% of patients experienced TRAEs of all grade and grade ≥3 respectively. The most common TRAE was hand-foot syndrome. 62.5% of single agent cabozantinib patients had any grade TRAE and no such patients had grade ≥3 TRAE. Conclusions: Cabozantinib had good anti-tumour activity and survival outcomes with acceptable toxicity in aHCC patients with previous treatment by ICIs.

(1) Background: Cabozantinib is approved in sorafenib-exposed advanced hepatocellular carcinoma (aHCC). We evaluated the real-life pattern of use, efficacy, and tolerability of cabozantinib in aHCC. (2) Methods: This territory-wide study included consecutive aHCC patients who received cabozantinib between February 2018 and September 2020 in Hong Kong. The objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events (AE) were assessed. (3) Results: Overall, 42 patients were included. Approximately 83.3% had Child-Pugh A cirrhosis. About 64.3% received cabozantinib as a single agent, and the remaining 35.7% received cabozantinib as an add-on to immune checkpoint inhibitors (ICIs). For single-agent patients, the median follow-up was 6.7 months. The ORR was 3.7%, DCR was 44.4%, and the median OS was 8.28 months. About 74.1% of patients experienced any AEs with 7.4% having grade ≥3 AEs. Among patients who received prior ICIs (n = 16), the ORR was 6.3%, and the median OS was 8.28 months. An exploratory analysis of patients who received cabozantinib as an add-on to ICIs showed an ORR of 6.7% and a median OS of 15.1 months, with 73.3% having any AE and 13.3% having grade ≥3 AEs. (4) Conclusions: Cabozantinib had good anti-tumor activity, survival benefits, and acceptable tolerability in real-life aHCC patients.