Combined hepatocellular cholangiocarcinoma: A clinicopathological update

Table 3 Reported cohorts of combined hepatocellular-cholangiocarcinoma patients treated with immunotherapy

Ref.	Study type	Drug	Number of patients	Outcome
Tahover et al[55]	Case report	Ipilimumab and nivolumab, followed by nivolumab	1	ECOG performance status improved from 3 to 0. Repeated PET-CT showed near complete response, ca125 decreased by 90% and liver function tests normalized
Rizell et al[56]	Case report	Pembrolizumab	1 (Post resection, pulmonary metastasis)	Complete remission of the pulmonary metastases. There was no sign of cancer recurrence neither in the liver nor in the lungs at 33 months after the start of the checkpoint inhibition treatment
Diab et al[57]	Retrospective case series	Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor	6	Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 yr, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed
Saito et al[58]	Case report	Atezolizumab plus bevacizumab	1 (3 months after resection, multiple lymph node metastases)	7.5-month progression-free survival
Satake et al[52]	Case series	Atezolizumab plus bevacizumab	6	Three partial responses and one stable disease as the best responses
Saint et al[59]	Case report	Pembrolizumab	1	Complete response which was maintained over time along with toxicity-free tumor control after 18 months treatment
Pomej et al[53]	Retrospective, multicenter cohort	Three (43%) patients received atezolizumab plus bevacizumab, two (29%) patients were treated with nivolumab alone, and one (14%) patient each received pembrolizumab alone and nivolumab in combination with TACE, respectively	7	Overall response rate was 29% with a disease control rate of 43%
Zhou et al[60]	Case report	Sintilimab, lenvatinib, and nab-paclitaxel	1

ECOG: Eastern cooperative oncology group; CT: Computed tomography; TACE: Trans arterial chemoembolization.