A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer.

BACKGROUND: The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. METHODS: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival. RESULTS: The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported. CONCLUSIONS: The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed.

Long-Term Pulmonary Outcomes of a Feasibility Study of Inverse-Planned, Multibeam Intensity Modulated Radiation Therapy in Node-Positive Breast Cancer Patients Receiving Regional Nodal Irradiation.

PURPOSE: Multibeam intensity modulated radiation therapy (IMRT) enhances the therapeutic index by increasing the dosimetric coverage of the targeted tumor tissues while minimizing volumes of adjacent organs receiving high doses of RT. The tradeoff is that a greater volume of lung is exposed to low doses of RT, raising concern about the risk of radiation pneumonitis (RP). METHODS AND MATERIALS: Between July 2010 and January 2013, patients with node-positive breast cancer received inverse-planned, multibeam IMRT to the breast or chest wall and regional nodes, including the internal mammary nodes (IMNs). The primary endpoint was feasibility, predefined by dosimetric treatment planning criteria. Secondary endpoints included the incidence of RP grade 3 or greater and changes in pulmonary function measured with the Common Terminology Criteria for Adverse Events version 3.0 scales, pulmonary function tests and community-acquired pneumonia questionnaires, obtained at baseline and 6 months after IMRT. Clinical follow-up was every 6 months for up to 5 years. RESULTS: Median follow-up was 53.4 months (range, 0-82 months). Of 113 patients enrolled, 104 completed follow-up procedures. Coverage of the breast or chest wall and IMN was comprehensive (median 48.1 Gy and 48.9 Gy, respectively). The median volume of lung receiving a high dose (V20Gy) and a low dose (V5) was 29% and 100%, respectively. The overall rate of respiratory toxicities was 10.6% (11/104), including 1 grade 3 RP event (0.96%). No differences were found in pulmonary function test or community-acquired pneumonia scores after IMRT. The 5-year rates of locoregional recurrence-free, disease-free, and overall survival were 93.2%, 63.6%, and 80.3%, respectively. CONCLUSIONS: Multibeam IMRT in patients with breast cancer receiving regional nodal irradiation was dosimetrically feasible, based on early treatment planning criteria. Despite the large volume of lung receiving low-dose RT, the incidence of grade 3 RP was remarkably low, justifying inverse-planned IMRT as a treatment modality for patients with high-risk breast cancer in whom conventional RT techniques prove inadequate.

A Randomized Trial of Mometasone Furoate 0.1% to Reduce High-Grade Acute Radiation Dermatitis in Breast Cancer Patients Receiving Postmastectomy Radiation.

PURPOSE: A 2-arm, double-blinded randomized trial was conducted to evaluate the efficacy of 0.1% mometasone furoate (MF) versus Eucerin Original (E) cream in preventing the development of moderate to severe acute radiation dermatitis (ARD) in breast cancer patients receiving postmastectomy radiation (PMRT). METHODS: Breast cancer patients undergoing chest wall with or without nodal radiation therapy (RT) (50 Gy) were eligible. Randomization (1:1) was to MF or E, applied twice daily from day 1 of PMRT to 14 days after PMRT. Patients were stratified by RT technique, body mass index, and reconstruction status. Daily bolus of 3 to 10 mm was applied in all patients. The primary endpoint was the development of provider-assessed grade ≥2 (Common Terminology Criteria for Adverse Events version 4.03) ARD with moist desquamation or any grade ≥3 dermatitis. Secondary endpoints were time to occurrence of maximum-grade dermatitis and patient-reported skin symptoms using a skin-related quality of life questionnaire, Skindex-16. Assessments were performed at baseline, weekly during PMRT, and 2 weeks after PMRT. RESULTS: 124 patients were enrolled between May 2013 and February 2016. Of those, 35% had pathologic stage III disease, 6% had cT4d disease, and 68% underwent reconstruction. Sixty percent received 3-dimensional conformal RT with photons only to the chest wall, 18% received electrons and photons, and 23% received inverse-planned intensity modulated RT. Groups were well balanced for age, skin type, and stage. The rate of moist desquamation was 54.8% in the entire cohort, with a significantly reduced incidence in the MF arm than in the E arm (43.8% vs 66.7%; P = .012). The MF arm had a lower incidence of maximum skin toxicities (P = .036) and longer time to development of grade 3 dermatitis (46 days vs 35.5 days, respectively; P ≤ .001). There was no difference in patient-reported skin outcomes between arms. CONCLUSIONS: Breast cancer patients receiving MF during PMRT experienced significantly reduced rates of moist desquamation in comparison with a control cream.