Selected Articles from This Issue
Journal: Clinical Cancer Research (2021)

Many breast cancers rely on estrogen receptor (ER) signaling, and selective ER degraders (SERDs) are an attractive therapeutic option. Although the SERD fulvestrant is approved for ER-positive breast cancer, its utility is limited by dosing restrictions. Jhaveri and colleagues assessed LSZ102, an investigational oral SERD, in a phase I trial. LSZ102 was administered either alone or in combination with ribociclib (a CDK4/6 inhibitor) or alpelisib (a PI3K inhibitor). LSZ102 was well tolerated alone and in combination with ribociclib. On-treatment biopsy assessments revealed ER reductions. Clinical benefit was observed, especially in combination with ribociclib. These results are encouraging, and the combination of LSZ102 and ribociclib warrants further clinical study.Preclinical work has shown that epigenetic modulation improves the efficacy of checkpoint blockade and promotes a more favorable tumor immune microenvironment. To assess the clinical efficacy of this strategy, Torres and colleagues conducted a phase I clinical trial combining entinostat, an HDAC inhibitor, with nivolumab with or without ipilimumab in patients with advanced solid tumors. Overall, the objective response rate was 16%, and one complete response was observed in triple-negative breast cancer. Combination treatment led to evidence of increased anti-tumor immunogenicity. The preliminary evidence of efficacy and immune modulation observed in this trial will lead to further clinical assessment of epigenetic modulation and checkpoint blockade.The combination of immune checkpoint blockade and angiogenesis inhibition has been an effective treatment strategy in advanced renal cell carcinoma (RCC). However, effective therapeutic approaches are needed after antiangiogenic tyrosine kinase inhibitor failure. In this phase II study, Qu and colleagues assessed the combination of camrelizumab (a PD-1 inhibitor) and famitinib (a structural analogue of the tyrosine kinase inhibitor sunitinib with improved inhibition activities) in patients with advanced/metastatic RCC regardless of prior treatment. The combination demonstrated robust objective responses, substantial and sustained reductions in tumor burden, and long progression-free survival, both in treatment-naive and previously treated patients. No unexpected toxicities were observed, and safety profile was consistent with each component as a single agent. Thus, camrelizumab plus famitinib warrants further clinical investigation as a feasible treatment strategy for advanced/metastatic RCC.An accurate test of minimal residual disease in HPV-associated cancers could direct adjuvant therapy to only the patients in greatest need. Leung and colleagues designed a novel next-generation sequencing approach (HPV-seq) to enable more sensitive detection of HPV ctDNA in low-disease burden settings. HPV--seq revealed accurate genotyping and detected 20-fold lower levels of HPV ctDNA than digital PCR. Furthermore, detectable HPV ctDNA at end-of-treatment was associated with inferior progression-free survival with 100% sensitivity and 67% specificity for recurrence. Thus, HPV-seq enables ultrasensitive detection of HPV ctDNA and shows promise as a tool for monitoring disease burden in HPV-related cancers.