RESUMO
Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m2 weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n = 4/13, 95% CI: 10-61%) and 43% for pembrolizumab/capecitabine (n = 6/14, 95% CI: 18-71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor-infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. The clinical trial registration is NCT02734290.
RESUMO
BACKGROUND: Both MRI and breast-specific gamma imaging are tools for surgical planning in newly diagnosed breast cancer. Breast-specific gamma imaging (BSGI) is used less frequently although it is of similar utility and lower cost. We compared the diagnostic and cost efficacy of BSGI with MRI. METHODS: Retrospective review of 1,480 BSGIs was performed in a community breast health center, 539 had a new diagnosis of cancer, 75 patients having both MRI and BSGI performed within 2 months of each other. Institutional charges for BSGI ($850) and MRI ($3,381) were noted. RESULTS: BSGI had a sensitivity of 92%, specificity of 73%, positive predictive value of 78%, and negative predictive value of 90%. This compared favorably with MRI that had sensitivity of 89%, specificity 54%, positive predictive value 67%, and negative predictive value 83%. The accuracy of BSGI was higher at 82% vs MRI at 72%. Total cost of MRI imaging was $253,575 vs BSGI at $63,750. CONCLUSIONS: BSGI is a cost-effective and accurate imaging study for further evaluation of dense breast tissue and new diagnosis of cancer.
