Anita T. Shaffer

Combination regimens that pair nab-paclitaxel with PD-L1 checkpoint blockade immunotherapy agents are emerging as a robust area of investigation in triple-negative breast cancer, bolstered by clinical trial results that establish the chemotherapeutic agent as an effective partner for other therapies.

The noninvasive testing that has long been the goal of solid tumor analysis is making its presence felt in lung cancer, and other malignancies likely will not be far behind, experts say. Although many potential uses for liquid biopsies are envisioned, much work remains to be done to establish the clinical utility of these tests.

Two of the most noteworthy developments in the oncology field during 2016 were the continued expansion of checkpoint blockade immunotherapy agents into more cancer types and the federal government’s plans for funding and remaking the research paradigm.

Tepotinib, an investigational small molecule that targets a recently identified aberration in the MET gene, is moving forward rapidly in clinical development for patients with non–small cell lung cancer who harbor the mutation, raising hopes that a more specific attack on the signaling pathway will lead to a new therapy for a significant subgroup of individuals with the disease.

Aromatase inhibitor (AI) therapy may pose a risk of cardiovascular disease to postmenopausal women with early-stage breast cancer, raising the possibility of a long-term complication in an era of growing survivorship when patients are treated with estrogen-targeting drugs for years.

An attempt to strengthen neoadjuvant treatment of patients with locally advanced HR-positive and HER2-positive breast cancer by adding estrogen deprivation therapy to a standard regimen failed to significantly improve response rates but did illustrate the extensive toxicity of the chemotherapy agents used in this setting.

The genomic landscape of recurrent metastatic estrogen receptor–positive breast cancer differed significantly from the mutational profile of primary disease in a study that sheds light on acquired resistance mechanisms to anticancer therapies.

A multipronged attack on the tumor vasculature network is at the heart of a recently launched clinical trial aimed at developing new therapeutic options for women with advanced, recurrent, platinum-resistant ovarian cancer.

A novel immune checkpoint called PVRIG is currently in development.

A clinical trial that utilizes a novel radiolabeled antibody–drug conjugate to pretreat older patients with relapsed or refractory acute myeloid leukemia as part of a stem cell transplantation regimen is aimed at creating improved outcomes for a high-risk population with limited therapeutic alternatives.

It has been about 18 months since the first immunotherapy checkpoint agent was approved for patients with non–small cell lung cancer. Now there are 3 monoclonal antibodies that target the PD-1/PD-L1 pathway on the market for the tumor type and the focus has shifted rapidly to establishng immunotherapy as a new frontline standard.

Pembrolizumab monotherapy reduced the risk of death by 27% compared with chemotherapy for patients with advanced urothelial carcinoma whose disease progressed after prior treatment.

Although there are no drugs that target TP53 mutations in any tumor type, a recent analysis of a non–small cell lung cancer sample set raises the prospect that a more detailed understanding of this aberration eventually could help direct therapy.

A dual approach to overcoming resistance to endocrine therapy in patients with advanced hormone receptor-positive breast cancer is under investigation in a phase III trial that adds the novel drug entinostat to standard exemestane therapy after disease progression.

A new generation of drugs has proved highly effective against the hepatitis C virus but there is conflicting evidence about whether the therapies promote cancer recurrence in infected patients with hepatocellular carcinoma who already have responded to curative treatment.

Two competing methods of delivering locoregional therapy to patients with hepatocellular carcinoma both have advantages and may be most successful in subgroups of individuals with intermediate-stage disease.

Nivolumab continues to post durable responses in patients with advanced hepatocellular carcinoma regardless of whether they had hepatitis B or C or whether they had received prior treatment with sorafenib.

After 9 years of failed trials for once-promising drugs, regorafenib (Stivarga) has emerged as the clear choice for second-line therapy in advanced hepatocellular carcinoma after demonstrating survival improvements for patients whose disease has progressed after systemic treatment.

Early evidence suggests that the combination of locoregional therapy with an immune checkpoint inhibitor is a safe and effective strategy to pursue for patients with advanced hepatocellular carcinoma.

Although it has been nearly 10 years since a new drug was approved for the treatment of patients with hepatocellular carcinoma, the past decade has been marked by advances on the scientific and radiology fronts and the prospects for the development of new therapies are bright.

An assay that would evaluate the immune status of patients with colon cancer is poised to become the first of a series of Immunoscore tests for various tumor types.

The optimal use of emerging assays that characterize molecular abnormalities from plasma in late-stage non–small cell lung cancer will be to augment tissue biopsies at initial diagnosis and to evaluate patients for second- and third-line therapies.

Although it has been nearly 10 years since a new systemic drug has been approved for the treatment of patients with hepatocellular carcinoma, the field is changing rapidly due to new therapies for a prime underlying cause of the disease and advances in interventional radiology.

Lutathera (lutetium Lu 177 dotatate) has demonstrated "quite striking" results with a favorable safety profile as a therapy for patients with progressive midgut neuroendocrine tumors in the first randomized phase III study to evaluate a radiolabeled somatostatin analogue in this treatment setting.

Suzanne L. Topalian, MD, discusses progress in PD-1/PD-L1 immunotherapies and the prospects for developing biomarkers to better identify patients who would benefit from the new agents.

At a time when PD-1 inhibitors are dominating the immunotherapy field, a team of researchers is seeking to use groundbreaking CRISPR gene editing technology for the first time in human beings to create an engineered T-cell agent that would knock out the gene that controls the immune checkpoint’s activity.

Amid growing evidence of their importance in the immune system, myeloid-derived suppressor cells are gaining traction as a target for anticancer therapies.

After years of anticipation, biosimilar versions of the most widely administered monoclonal antibodies in oncology care are moving closer to fruition for the US market, starting with a new form of trastuzumab (Herceptin).

Patients with lung cancer who participated in a web-based system for reporting and tracking their symptoms achieved dramatic gains in survival compared with individuals who were followed with typical protocols.

IMAB362 reduced the risk of death or progression by approximately 50% when added to standard chemotherapy for patients with CLDN18.2-positive advanced gastric cancers.