Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti–PD-1 for patients with anti–PD-1–refractory tumors

Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti–programmed cell death protein–1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti–PD-1 agent might be a strategy to revert anti–PD-1 resistanc

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible. A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p 6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p  Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET