Current Oncology Reports

Margin assessment remains a critical component of oncologic care for head and neck cancer patients. As an integrated team, both surgeons and pathologists work together to assess margins in these complex patients. Differences in method of margin sampling can impact obtainable information and effect outcomes. Additionally, what distance is an “adequate or clear” margin for patient care continues to be debated. Ultimately, future studies and potentially secondary modalities to augment pathologic assessment of margin assessment (i.e., in situ imaging or molecular assessment) may enhance local control in head and neck cancer patients.

This article provides a comprehensive review of antibody-drug conjugates (ADCs) under investigation in gynecologic cancers. The structure and function of ADCs are reviewed with a focus on clinical benefit as well as toxicity profiles. Several ADCs with various target antigens have been investigated in ovarian, cervical, and endometrial cancer. ADCs have consistently demonstrated favorable safety/tolerability profiles both as monotherapy and in combination therapy. In ovarian cancer, response rates have ranged from 9 to 46% for monotherapy with response rates as high as 83% in combination therapy. In patients with cervical cancer with progressive disease despite doublet therapy and bevacizumab, response rates as high as 24% have been observed. ADCs represent a rapidly evolving field of targeted therapy which have demonstrated notable clinical benefit both as monotherapy but also in combination therapy with an overall favorable toxicity profile. With continued refinement of the target biomarkers utilized, improved clinical benefit is likely to be observed.

This review delves into the prospects and challenges offered by a potential pan-histological utilization of trastuzumab deruxtecan (T-DXd) in patients with advanced solid tumors. The HER2-targeted antibody-drug conjugate (ADC) T-DXd has shown broad activity across cancer types, with current indications for patients with biomarker-selected breast, gastric, and non-small-cell lung cancer and relevant activity observed in multiple histology-specific trials. Moreover, two recently reported phase 2 trials (DESTINY-Pantumor02 and HERALD) have supported the potential for a pan-cancer utilization of this ADC in patients with advanced cancers expressing HER2 or with HER2 amplifications. By improving the delivery of cytotoxic chemotherapy, ADCs have allowed for meaningful clinical advantages in broad populations of cancer patients, often leading to survival advantages over conventional chemotherapy. Notably, the broad spectrum of activity of certain ADCs has led to the hypothesis of a histology-agnostic utilization based on detecting specific biomarkers, similar to what is already established for certain targeted treatments and immunotherapy. To date, T-DXd has shown the broadest activity across cancer types, with current approvals in breast, gastric, and lung cancer, and relevant antitumor activity observed in a multiplicity of additional cancer types. The optimization of the drug dose, identification of predictive biomarkers, and clarification of mechanisms of resistance will be critical steps in view of a pan-histological expansion in the use of T-DXd.

Standardized response criteria for lymphoma are critical for the evaluation of new therapies. Widely adopted recommendations, most recently the Lugano classification, have been developed primarily for assessment of conventional chemotherapeutic regimens. More recently, several classes of drugs, including immunomodulatory agents, B cell receptor pathway targeting kinases, and checkpoint (PD-1, PDL-1) inhibitors have demonstrated impressive activity in a broad range of histologies. However, they may be associated with features during treatment suggestive of progressive disease despite clinical benefit. Immune response criteria have been proposed for solid tumors, and a modification is needed to be more applicable to lymphomas. Following treatment, conservative use of imaging is recommended based on clinical indications. As newer targeted agents with unique mechanisms of action are developed, current response and follow-up criteria must be made sufficiently flexible for optimal evaluation.