Abstract
Background: We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers. Methods: There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had ≥2 lesions; only one was irradiated (8 Gy × 3 for first half; 17 Gy × 1 for second half in each stratum) and the other(s) followed for response. Results: Of the 24 patients, 20 (83%) had treatment-related adverse events (AEs) (all grade 1 or 2). There were eight grade 3 AEs, none treatment related. There were no dose-limiting toxicities or grade 4/5 AEs. Stratum 1: two patients (of 12) with progression on prior PD-1 blockade experienced prolonged responses (9.2 and 28.1 months). Stratum 2: one patient experienced a complete response and two had prolonged stable disease (7.4 and 7.0 months). Immune profiling demonstrated that anti-PD-1 therapy and radiation induced a consistent increase in the proliferation marker Ki67 in PD-1-expressing CD8 T cells. Conclusions: HFRT was well tolerated with pembrolizumab, and in some patients with metastatic NSCLC or melanoma, it reinvigorated a systemic response despite previous progression on anti-PD-1 therapy. Clinical Trial Registration: NCT02303990 (www.clinicaltrials.gov).
Original language | English |
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Pages (from-to) | 1200-1207 |
Number of pages | 8 |
Journal | British Journal of Cancer |
Volume | 119 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2018 |
Keywords
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antineoplastic Agents, Immunological/therapeutic use
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Chemoradiotherapy
- Disease-Free Survival
- Female
- Humans
- Lung Neoplasms/drug therapy
- Male
- Melanoma/drug therapy
- Middle Aged
- Neoplasm Metastasis/drug therapy
- Radiation Dose Hypofractionation
- Skin Neoplasms/drug therapy