Efficacy and safety of immune checkpoint blockade in self-identified Black patients with advanced non-small cell lung cancer.

BACKGROUND: To the authors' knowledge, race-based differences in efficacy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) have not been studied to date due to the underrepresentation of patients of minority backgrounds in pivotal trials. In the current study, the authors examined real-world differences in outcome in a diverse patient population. METHODS: The authors retrospectively analyzed the clinical outcomes of patients with advanced NSCLC who were treated with single-agent immune checkpoint blockade (ICB) between 2013 and July 2018 at Winship Cancer Institute of Emory University in Atlanta, Georgia. Primary efficacy comparison between Black patients and White patients was performed using bivariate and multivariate analyses for overall survival (OS) and progression-free survival (PFS). RESULTS: Data from 257 patients were analyzed. The median age of the patients was 69 years; 50.6% of the patients were female, 63.4% were White, 29.5% were Black, and 7.1% of the patients were of "other" race. ICB was the first-line treatment in 51 patients (19.9%), the second-line treatment in 161 patients (62.6%), and the third-line treatment in 33 patients (12.9%). The most commonly used agents were nivolumab (49.0%), pembrolizumab (25.2%), and atezolizumab (21.3%). No differences with regard to OS (P = .839) and PFS (P = .235) were noted between Black and White patients. The sample overall response rate was 20.6% (15.2% in Black patients and 23.1% in White patients). No differences with regard to OS (P = .081) and PFS (P = .176) were observed between female and male patients. The rate of immune-related adverse events was found to be similar in Black and White patients (20.0% vs 29.9%; P = .148). On multivariate analysis, race was not found to be significantly associated with OS or PFS. CONCLUSIONS: Real-world analysis of the authors' institutional experience demonstrated similar efficacy and tolerability of ICB in Black versus White patients with advanced NSCLC. Larger multi-institutional studies including other US minority populations would make the findings of the current study more generalizable.

Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia: A Case Report.

Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

Toxicities of systemic agents in squamous cell carcinoma of the head and neck (SCCHN); A new perspective in the era of immunotherapy.

Squamous cell carcinoma of the head and neck (SCCHN) is a difficult to treat malignancy and represents the seventh most common cancer worldwide. Systemic therapy has a critical role in the treatment of locally advanced and recurrent/metastatic disease. Cytotoxic chemotherapy has been primarily used along with radiation and surgery, with cisplatin being the standard of care choice of therapy. When contraindications to cisplatin exist, other agents such as carboplatin, taxanes, 5-fluorouracil, and cetuximab are used. Similarly, in the advanced or metastatic setting, platinum agents, taxanes and cetuximab have been predominantly utilized. With the recent approval of novel agents such as pembrolizumab and nivolumab, and their distinct toxicity profiles, an understanding of the potential sequelae of the different systemic agents is essential to the careful selection of agents in the advanced disease setting. Going forward, choosing novel agents will be weighed against traditional chemotherapy, and understanding the toxicities at stake is critical in this process. In addition to providing an overview of the toxicity profile of the different systemic agents, we also provide a perspective into the future of SCCHN treatment.

The Evolving and Future Role of Taxanes in Squamous Cell Carcinomas of the Head and Neck: A Review.

IMPORTANCE: Since their discovery in the 1970s, taxanes have maintained widespread clinical use in solid tumors, including squamous cell carcinoma of the head and neck (SCCHN), but SCCHN remains a difficult malignancy to treat, often requiring a multidisciplinary approach involving surgery, radiotherapy, and chemotherapy. Taxanes have been heavily studied in the treatment of SCCHN, and their use is currently in the setting of induction chemotherapy with the TPF (docetaxel, FU, cisplatin) regimen for locally advanced SCCHN, as well as in the concurrent therapy setting. However, there is still no clear guideline or indication for the use of taxanes in SCCHN. OBSERVATIONS: A literature search was completed in PubMed using the search terms "taxane," "head and neck cancer," "docetaxel," "paclitaxel," and "chemotherapy," for articles published between 1990 to 2015. In this review, we provide an overview of the evidence thus far supporting the use of taxanes in the concurrent, induction, and adjuvant settings, as well as their use in the treatment of recurrent or metastatic SCCHN. For locally advanced disease, docetaxel is part of the first line regimen for induction therapy, although the superiority of sequential therapy compared with concurrent therapy is still in question. In addition, several studies have shown at least equivalent outcomes for regimens including taxanes compared with standard platinum-based regimens. In the adjuvant setting, RTOG (Radiation Therapy Oncology Group) 1216 is looking into the prospect of docetaxel as a first-line agent for systemic therapy following surgery. In metastatic disease, various second-line regimens include taxanes, and their use is being considered in first-line therapies as well. Several phase 3 trials involving taxanes are underway, with the possibility that they will provide results that increase taxane use in SCCHN. In addition to reviewing their current use, we also provide an analytical discussion of the projected future role of taxanes in the management of SCCHN. Ongoing and future studies involving taxanes are also discussed. CONCLUSIONS AND RELEVANCE: While the current role of taxane use in SCCHN remains to be established, ongoing and future studies involving taxanes will hopefully solidify their role in the treatment of SCCHN. The future role of taxanes will also be influenced by the introduction of novel taxanes, as well as immunotherapy in the treatment of SCCHN.

The Future Prospects of Immune Therapy in Gastric and Esophageal Adenocarcinoma.

The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers. Programmed death ligand 1 (PDL1) overexpression, a possible biomarker predicting response to immune checkpoint inhibitors, approaches forty percent in esophageal and gastric cancers. Translational and molecular studies have shown that esophageal cancers are possible candidate malignancies for immune checkpoint inhibition. In this review, we plan to highlight the mechanisms, preclinical, and early clinical data that provide insight on the role of immune therapeutics in esophageal cancers.

Complete Remission of Acute Myeloid Leukemia following Cisplatin Based Concurrent Therapy with Radiation for Squamous Cell Laryngeal Cancer.

Acute myeloid leukemia (AML) is a myeloid disorder with several established treatment regimens depending on patient and leukemic factors. Cisplatin is known to have strong leukemogenic potential and is rarely used even as salvage therapy in relapsed or refractory AML. We present a patient simultaneously diagnosed with AML and squamous cell carcinoma of the larynx, who was found to be in complete remission from AML following treatment with cisplatin based chemoradiotherapy for his laryngeal cancer.