Selected Articles from This Issue

Recently, immune checkpoint inhibitors have shown promising results in advanced hepatocellular carcinoma (HCC). In a single-arm phase II study, Lee and colleagues evaluated the efficacy and safety of avelumab, anti-PD-L1, in patients with advanced HCC previously treated with sorafenib. Avelumab showed an ORR of 10% and disease control rate of 73.3%. The median time to progression was 4.4 months (95% CI, 2.9–5.9), and median OS was 14.2 months (95% CI, 9.5–18.9). Avelumab was well tolerated with manageable toxicity. PD-L1 expression did not correlate with response rate. Patients who received longer duration of sorafenib had better outcome on avelumab. The study results show that avelumab may be a treatment option in sorafenib refractory advanced HCC.

Approximately 30% of patients with chronic lymphocytic leukemia (CLL) can be grouped into subsets with stereotyped B-cell receptor immunoglobulin (BcR IG) displaying similarity in the heavy complementarity-determining region 3 (VH CDR3). Rovida and colleagues show that immunogenic epitopes can be isolated from the consensus VH CDR3 sequence of both human and murine stereotyped CLL, processed and presented by CLL cells and recognized by specific T cells. Immunization of EμTCL1 CLL mouse model reduced leukemia development and increased overall survival of the animals. This data highlight the immunogenicity of stereotyped VH CDR3 sequences and support the feasibility and efficacy of their use for cancer vaccines with the potential of targeting groups of patients with CLL.

The carcinoembryonic antigen CEACAM5 is upregulated in neuroendocrine prostate cancer (NEPC), which lacks effective therapies. DeLucia and colleagues analyzed lethal prostate cancers by multiplex immunofluorescence to demonstrate minimal coexpression of CEACAM5 with PSMA, PSCA, and Trop. in NEPC. A functional basis for CEACAM5 expression was identified in that the pioneer factor ASCL1 induces CEACAM5 via chromatin remodeling during neuroendocrine transdifferentiation. Further, the CEACAM5 antibody-drug conjugate, labetuzumab govitecan, was redirected to NEPC and showed marked efficacy in xenograft models. Based on these promising findings, a phase I/II clinical trial of labetuzumab govitecan in men with NEPC is now in development.

Selective MET tyrosine kinase inhibitors (TKI), such as capmatinib and tepotinib, have demonstrated unprecedented activity in MET exon 14-altered lung cancers, but response rates are still modest relative to targeted therapies in other oncogene-driven lung cancers (i.e., EGFR). Guo and colleagues conducted genomic and proteomic testing on pretreatment samples from patients treated with a MET tyrosine kinase inhibitor (TKI). Genomic factors outside activating MET exon 14-alterations did not predict benefit with TKI, whereas MET expression by immunohistochemistry or mass spectrometry may predict benefit. These findings highlight that proteomic factors may modify response to TKI in MET exon 14-altered lung cancers.