Nature Reviews Clinical Oncology最新文献

A diverse range of viruses have well-established roles as the primary driver of oncogenesis in various haematological malignancies and solid tumours. Indeed, estimates suggest that approximately 1.5 million patients annually are diagnosed with virus-related cancers. The predominant human oncoviruses include Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B and C viruses (HBV and HCV), human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV1), and Merkel cell polyomavirus (MCPyV). In addition, although not inherently oncogenic, human immunodeficiency virus (HIV) is associated with immunosuppression that contributes to the development of AIDS-defining cancers (specifically, Kaposi sarcoma, aggressive B cell non-Hodgkin lymphoma and cervical cancer). Given that an adaptive T cell-mediated immune response is crucial for the control of viral infections, increasing research is being focused on evaluating virus-specific T cell therapies for the treatment of virus-associated cancers. In this Review, we briefly outline the roles of viruses in the pathogenesis of these malignancies before describing progress to date in the field of virus-specific T cell therapy and evaluating the potential utility of these therapies to treat or possibly even prevent virus-related malignancies.

Adults with B cell-precursor acute lymphoblastic leukaemia (BCP-ALL) negative for minimal residual disease (MRD) after induction chemotherapy have a superior prognosis relative to those with MRD⁺ status, although many will eventually have disease relapse. Now, data from the phase III E1910 trial demonstrate that addition of the CD19 × CD3 bispecific T cell engager blinatumomab to consolidation chemotherapy improves overall survival (OS) in this setting.

Patients received standard-of-care induction chemotherapy. Those with an MRD^– complete response (<0.01% leukaemic cells in bone marrow; 224 of 488 patients) were randomly allocated (1:1) to receive standard-of-care consolidation chemotherapy with or without blinatumomab, followed by standard maintenance therapy in both groups. OS in patients with MRD^– disease was the primary end point.

Patients with extensive-stage small-cell lung cancer (ES-SCLC) usually receive platinum-based chemotherapy plus an immune-checkpoint inhibitor (ICI) as first-line therapy, although disease relapse is a concern. Now, data from the phase III ETER701 trial demonstrate that the combination of the anti-angiogenic agent anlotinib plus the anti-PD-L1 antibody benmelstobart and chemotherapy has promising efficacy in this setting.

Patients were randomly allocated to receive anlotinib plus benmelstobart and chemotherapy (triplet regimen; n = 246), anlotinib plus placebo and chemotherapy (doublet regimen; n = 245) or double placebo plus chemotherapy (the standard of care in China at the time of trial design) (n = 247). Progression-free survival (PFS) and overall survival (OS) were the co-primary end points.

Patients with recurrent advanced-stage and/or metastatic cervical cancer typically have a poor prognosis with limited treatment options available. Now, data from the phase III innovaTV 301 trial demonstrate the efficacy of the tissue factor-targeted antibody–drug conjugate tisotumab vedotin in this setting.

A total of 502 patients with advanced-stage and/or metastatic cervical cancer who previously received 1 (62.8%) or 2 (36.8%) lines of therapy were randomly assigned (1:1) to receive tisotumab vedotin versus investigator’s choice of chemotherapy (including topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed). Overall survival (OS) was the primary end point.