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Background: Heat shock protein 90 (HSP90) is a molecular chaperone required for stabilization of client proteins over-activated in triple-negative breast cancer (TNBC). Over-expression of HSP90 client proteins has been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent inhibitor of HSP90 that could improve paclitaxel efficacy when administered in combination. Design: This phase Ib trial administered onalespib with paclitaxel in patients with advanced TNBC to assess safety and establish a recommended phase II dose (RP2D). Objectives: The primary objectives were determining the dose-limiting toxicities and maximum tolerated dose of combination therapy. Secondary objectives included pharmacokinetic (PK) analysis and determination of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Methods: Patients with advanced TNBC were treated with standard dose intravenous paclitaxel in combination with intravenous onalespib at doses ranging from 120 to 260 mg/m 2 administered on days 1, 8, and 15 of a 28-day cycle using a standard 3 + 3 design. A total of 15 patients were enrolled to dose expansion cohort at RP2D to confirm safety profile. Results: Thirty-one patients were enrolled in the study, of which over 90% had received prior taxane therapy. Paclitaxel was given for metastatic disease in 23% of patients. Adverse events (AEs) included anemia (grade 3: 20%), lymphopenia (grade 3: 17%), and neutropenia (grade 3: 33%, grade 4: 4%). The most frequent grade ⩾3 non-hematologic AE was diarrhea (7%). The established RP2D was 260 mg/m 2 onalespib when given with paclitaxel at 80 mg/m 2 . PK analysis revealed a modest drug interaction profile for onalespib in the combination regimen. ORR was 20%. Three patients achieved complete responses, all of whom had received prior taxane therapy. Median DOR was 5.6 months; median PFS was 2.9 months. Conclusion: Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and RP2D was determined to be 260 mg/m 2 of onalespib. Combination therapy showed antitumor activity in patients with advanced TNBC. Trial registration: Onalespib and paclitaxel in treating patients with advanced TNBC https://clinicaltrials.gov/ct2/show/NCT02474173 .

We analyze the application of star formation rate calibrations using Hα and 22 μm infrared (IR) imaging data in predicting the thermal radio component for a test sample of three edge-on galaxies (NGC 891, NGC 3044, and NGC 4631) in the Continuum Halos in Nearby Galaxies—an EVLA Survey (CHANG-ES). We use a mixture of Hα and 24 μm calibration from Calzetti et al. and a linear 22 μm only calibration from Jarrett et al. on the test sample. We apply these relations on a pixel-to-pixel basis to create thermal prediction maps in the two CHANG-ES bands: L and C band (1.5 GHz and 6.0 GHz, respectively). We analyze the resulting nonthermal spectral index maps, and find a characteristic steepening of the nonthermal spectral index with vertical distance from the disk after application of all methods. We find possible evidence of extinction in the 22 μm data as compared to 70 μm Spitzer Multiband Imaging Photometer imaging in NGC 891. We analyze a larger sample of edge-on and face-on galaxy 25–100 μm flux ratios, and find that the ratios for edge-ons are systematically lower by a factor of 1.36, a result we attribute to excess extinction in the mid-IR in edge-ons. We introduce a new calibration for correcting the Hα luminosity for dust when galaxies are edge-on or very dusty. [ABSTRACT FROM AUTHOR]