Antibody-Drug Conjugates in Gynecologic Cancers.

OPINION STATEMENT: Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.

Efficacy of cyclin-dependent kinase 4/6 inhibitors in combination with hormonal therapy in patients with recurrent granulosa cell tumor of the ovary: A case series.

Cyclin-dependent kinase inhibitors are approved in combination with hormonal therapy for treatment of hormone receptor expressing breast cancers. Activity in hormone receptor expressing gynecologic cancers has been postulated. Granulosa cell tumor of the ovary is one such cancer, which is relatively resistant to traditional cytotoxic chemotherapy. We report a case series of 7 heavily pre-treated patients with recurrent granulosa cell tumor of the ovary with a cyclin-dependent kinase inhibitor in combination with hormonal therapy, with 3 patients demonstrating partial response and 2 with stable disease. As of the data cutoff, 3 patients remained on treatment and 5 were alive, with true medians for duration of treatment and overall survival not reached (medians at data cutoff of 64 weeks and 62 months respectively). The treatment was generally well tolerated, with 1 patient choosing to discontinue treatment due to grade 3 fatigue. This regimen represents a possible option in the treatment of granulosa cell tumor of the ovary, warranting further prospective study for this unmet need in this indolent disease which often requires many lines of treatment.

Evaluation of the head and neck cancer patient population and the incidence of hospitalization at an academic medical center.

PURPOSE: Patients with head and neck cancer are at risk for disease- and treatment-related toxicities that may be severe enough to require hospitalization. The risk factors associated with hospitalization in these patients are not well defined. METHODS: We conducted a single-center, retrospective observational study of patients with head and neck cancer receiving chemotherapy at an academic medical center infusion clinic in a one-year period. The primary objective was to characterize the head and neck cancer population at an academic medical center. Secondary objectives included describing the clinical and social factors associated with hospitalization. RESULTS: There were 109 patients with head and neck cancer included in the analysis. Of these patients, 38 (35%) were hospitalized. The factors that were significantly associated with hospitalization on univariable logistic regression were former alcohol abuse, being on a nonstandard of care chemotherapy regimen, and having a chemotherapy agent discontinued. On multivariable logistic regression, the factor that was significantly associated with hospitalization was having a chemotherapy agent discontinued. The most common reasons for hospitalization included shortness of breath/respiratory failure, fever/neutropenic fever, and infection. The most common new supportive care medications prescribed at discharge were stool softeners or laxatives and opioids. CONCLUSION: This study identified several factors which may be useful to identify patients as high risk for hospitalization and the next steps will be to determine and study the role of the pharmacist in preventing hospitalization of these patients. Further studies are needed to assess the impact of adding a pharmacist to the head and neck cancer multidisciplinary team.

Supratherapeutic INR resulting from the initiation of warfarin in a patient receiving axitinib.

Axitinib is a vascular endothelial growth factor receptor inhibitor indicated for advanced renal cell cancer after failure of one prior systemic therapy. We report a case where a patient receiving axitinib experienced a supratherapeutic INR soon after initiation of an age-appropriate warfarin dose. We propose two possible mechanisms for this interaction, including competitive protein binding and decreased metabolism. Close INR monitoring and dose adjustments of warfarin may be necessary in patients receiving concomitant axitinib and warfarin in order to decrease the risks associated with this interaction.