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A phase II, single arm study assessing the efficacy of pembrolizumab (Pembro) plus radiotherapy (RT) in metastatic triple negative breast cancer (mTNBC).
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2018
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Breast OncologyCancer ManagementImmunologySingle Arm StudyPathologyImmunotherapeuticsImmunotherapyRadiation MedicineOncologyTumor ImmunityRadiation OncologyMolecular OncologyPd-l1 ExpressionOverall Response RateCancer TreatmentImmune Checkpoint InhibitorBreast CancerMedicinePhase Ii
1017 Background: Overall response rates of 5-7% have been reported with checkpoint inhibitor monotherapy in PD-L1-unselected mTNBC as second line or subsequent therapy. RT is frequently used to enhance local control in mTNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. In this study, we evaluate the safety and efficacy of RT combined with pembro, a programmed death 1 (PD-1) inhibitor, in a phase II, single-arm, Simon two-stage, study in mTNBC. Methods: Eligible women had biopsy-proven mTNBC and ≥2 measurable sites of metastatic disease with at least one site requiring RT. PD-L1 expression was not required for study entry. A total RT dose of 3000 cGy was delivered in 5 daily fractions. Pembro was given intravenously at 200 mg within 3 days of the first RT fraction, then every 3 weeks +/-3 days until disease progression. The primary endpoint was overall response rate at week 13 in the non-irradiated lesions by RECIST v1.1. Secondary endpoints included safety and overall survival. Tumor biopsies were obtained at baseline and at week 7. Results: Of the 17 women enrolled, the median age was 52 y (range 37-73y), and the median number of prior cytotoxic therapies for metastatic disease was 3 (range 0 to 8). Of the 8 women not evaluable at 13 weeks: 5 died secondary to disease-related complications (at weeks 2, 6, 7, 8, and 9) and 3 progressed prior to week 13. Of the 9 women evaluable at week 13, 3 (33%) had a partial response, 1 (11%) had stable disease and 5 (56%) had disease progression. The stable disease response was durable for 22 weeks. The 3 partial responses represented 60%, 54%, and 34% decreases in tumor burden by RECIST v1.1 and were durable for 31, 21, and 40 weeks, respectively. Common toxicities were mild and included fatigue, myalgia and nausea. Conclusions: The combination of pembro and RT was well-tolerated with durable responses outside the RT field in 3/9 (33%) evaluable patients unselected for PD-L1 expression. Thus, the addition of RT to PD-1 blockade represents a promising strategy for improving response rates in pre-treated mTNBC. Clinical trial information: NCT02730130.