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Hyperprogressive disease (HPD) is a phenomenon defined as extremely rapid tumor progression within a short time following immunotherapy. To date, distinguishing which subgroups may be eligible for anti-PD-1/PD-L1 treatment has presented a clinical challenge. Moreover, no sufficiently convincing biomarkers of HPD have been identified. Herein, we present two cases of cancer patients who suffered from liver metastasis before immunotherapy. A 63-year-old man presented with cough and pain in right collarbone. He was finally diagnosed as suffering from right upper lobe adenocarcinoma with cTxN3M1c and stage IVB. First-line carboplatin plus pemetrexed chemotherapy combined with sintilimab anti-PD-1 was initiated after a multi-disciplinary discussion. In the second case, a 46-year-old female was diagnosed as moderately differentiated cervical squamous cell carcinoma. Widespread recurrence 2 years after extensive total hysterectomy for early cervical carcinoma. After six cycles of first-line chemotherapy and radiotherapy, the disease progressed and new-onset liver metastasis was detected. Pembrolizumab plus abraxane was administered as second-line therapy. After the rst cycle of anti-PD-1 therapy, in both cases, an extremely rapid radiological progression was observed in the liver metastases with obvious symptoms, while the primary tumor site and other metastatic lesions remained stable or shrunken. These aberrations were confirmed as HPD. The risk of HPD appears to be higher in patients with liver metastases. We believe that further research will pave the way for the discovery of more significant biomarkers of HPD.

Hyperprogressive disease in advanced cancer patients with liver metastasis treated with PD-1 inhibitors: two case reports