Antiproliferative action of ganetespib on melanoma cells.

<p>A. Ganetespib reduced viability. Cells were treated with varying amounts of ganetespib for 72 h and subjected to MTS assay. Data are expressed as mean±SD of three independent experiments. B. Mutational status and ganetespib IC50 of cell lines.</p

Effect of ganetespib on B-RAF, C-RAF and N-RAS expression in melanoma cells.

<p>Cells were treated with indicated amounts of ganetespib for 48 h and subjected to Western blot analysis.</p

Downregulation of multiple signaling pathways by ganetespib in melanoma cells.

<p>A. Cells were treated with indicated amounts of ganetespib for 24 h. B-RAF and N-RAS mutational status of each cell line is indicated. B. Cells were treated with 250 nM ganetespib for 48 and 72 h. Proteins levels were determined by Western blot analysis.</p

Ganetespib induced cell cycle arrest in melanoma cells.

<p>A. Cells were treated with 250 nM ganetespib for 24 hours, stained with PI and subjected to FACS analysis. B. Bar graphs of percentage of G1, S, and G2/M populations in control and ganetespib treated cells. C. Alterations in expression of multiple cell cycle regulating proteins induced by ganetespib. Cells were treated with indicated amounts of ganetespib for 48 h and analyzed by Western blot analysis. Relative expression levels of proteins (treated vs. control cells) are indicated.</p

Tumor control with PD-1 inhibition in a patient with concurrent metastatic melanoma and renal cell carcinoma

Blockade of the immunological checkpoint programmed death 1 (PD-1) using monoclonal antibodies has shown robust anti-tumor activity across a broad range of solid and hematological malignancies including melanoma and renal cell carcinoma (RCC). Characteristic markers such as the presence of tumor infiltrating lymphocytes, PD-L1 status, and mutational load may be equally or even more important in predicting clinical benefit from PD-1 pathway blockade than tumor histology. This case of a patient with concurrent metastatic melanoma and metastatic RCC, both of which were controlled for more than a year after a single dose of the anti-PD-1 antibody pembrolizumab, illustrates the potential to simultaneously treat distinct immunogenic tumors with anti-PD-1 agents

Immune Checkpoint Inhibitor Uptake in Real-World Patients With Malignant Pleural Mesothelioma

Introduction: Since the July 2017 National Comprehensive Cancer Network (NCCN) malignant pleural mesothelioma (MPM) guideline revision recommended second-line immune checkpoint inhibitors (ICIs), studies have suggested a greater response to ICI among patients with nonepithelioid MPM. Nevertheless, little is known regarding adoption of ICI in routine practice and if uptake differs by histologic subtype. Our objectives were to evaluate the real-world uptake of second-line ICI among patients with MPM and to reveal its association with histologic subtype. Methods: This was a multicenter, retrospective cohort study of real-world patients with MPM receiving at least two lines of systemic therapy between 2011 and 2019. We found the uptake of second-line ICI over time and evaluated the association between histologic subtype and ICI use, adjusting for relevant patient demographic and clinical factors. Results: Among the 426 patients with MPM in our cohort, 310 had epithelioid and 116 nonepithelioid histologic subtype. The median age was 73 years (interquartile range: 67–78). Overall, 144 patients (33.8%) received second-line ICI and 282 (66.2%) traditional chemotherapy. ICI uptake began in early 2015 before the NCCN guideline revision and increased rapidly to 2019. After the 2017 NCCN guideline revision, patients with nonepithelioid MPM histologic subtypes had more than 3 times the odds of receiving second-line ICI (OR = 3.26; 95% confidence interval: 1.41–7.54). Conclusions: Among real-world patients with MPM, second-line ICI uptake began over two years before the 2017 NCCN guideline recommendations and was associated with nonepithelioid histologic subtype after contemporary studies suggested increased clinical benefit in this population, reflecting prompt integration of scientific discovery into clinical practice

Comparison of neoadjuvant and adjuvant patients.

Comparison of neoadjuvant and adjuvant patients.</p

Summary of existing literature regarding neoadjuvant vs adjuvant chemotherapy in DMPM.

Summary of existing literature regarding neoadjuvant vs adjuvant chemotherapy in DMPM.</p

Patient demographics.

Patient demographics.</p

Overall survival by type of therapy.

Kaplan-Meier curves for overall survival by surgery and perioperative chemotherapy.</p