A Phase 2 Trial Combining Pembrolizumab and Palliative Radiation Therapy in Gastroesophageal Cancer to Augment Abscopal Immune Responses

• Published in: Advances in radiation oncology 2022-01, Vol.7 (1), p.100807-100807, Article 100807
• Main Authors: Chao, Joseph, MD, He, Ting-Fang, PhD, D'Apuzzo, Massimo, MD, PhD, Chen, Yi-Jen, MD, PhD, Frankel, Paul, PhD, Tajon, Michael, PhD, Chen, Helen, MD, Solomon, Shawn, BS, Klempner, Samuel J., MD, Fakih, Marwan, MD, Lee, Peter, MD
• Format: Article
• Language: English
• Subjects: Hematology, Oncology, and Palliative Medicine; Scientific
• ISSN: 2452-1094; 2452-1094
• DOI: 10.1016/j.adro.2021.100807

AbstractPurposeSingle agent PD-1 inhibitors have yielded durable responses in a minority of gastroesophageal cancers. Radiation therapy has been recognized to promote antitumor immune responses and may synergize with anti-PD-1 agents. We sought to evaluate if combining palliative radiation therapy with pembrolizumab can augment antitumor immune responses in gastroesophageal cancer. Methods and MaterialsPatients had metastatic gastroesophageal cancer with indication for palliative radiation therapy with ≥2 disease sites outside of the radiation field assessable for abscopal response and biopsies for laboratory correlative analyses. Palliative radiation was delivered to a dose of 30 Gy over 10 fractions. Pembrolizumab, 200 mg, was administered concurrently intravenously every 3 weeks until disease progression, unacceptable toxicity, or study withdrawal, for up to 2 years. Endpoints included PD-L1 expression in pre- and posttreatment biopsies and abscopal objective response rate per Response Evaluation Criteria in Solid Tumors. ResultsOf 14 enrolled patients, the objective response rate was 28.6% (95% confidence interval, 8.4%-58.1%), and the median duration of response was not reached (95% confidence interval, 6.9-NR months). Overall, 2 patients had treatment-related grade 3 to 4 adverse events with no grade 5 events. One patient discontinued therapy due to grade 4 colitis. We did not observe an association between radiation and abscopal changes in PD-L1 expression via assessment of an analogous PD-L1 Combined Positive Score, Tumor Proportion Score, Mononuclear Immune Cell Density Score, or proportion of PD-L1-expressing immune cells between pre- and posttreatment tumor biopsies. ConclusionsCombining palliative radiation therapy and pembrolizumab provided promising durable responses in this patient population but we were unable to definitively distinguish abscopal biologic changes. Biomarker analyses beyond PD-L1 expression are needed to better understand putative mechanisms and identify patients who will benefit from this approach.