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Table S1 from Phase II Single-arm Study of Durvalumab and Tremelimumab with Concurrent Radiotherapy in Patients with Mismatch Repair–proficient Metastatic Colorectal Cancer

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posted on 2023-03-31, 22:41 authored by Neil H. Segal, Andrea Cercek, Geoffrey Ku, Abraham J. Wu, Andreas Rimner, Danny N. Khalil, Diane Reidy-Lagunes, John Cuaron, T. Jonathan Yang, Martin R. Weiser, Paul B. Romesser, Zsofia K. Stadler, Anna M. Varghese, Karuna Ganesh, Rona Yaeger, Louise C. Connell, David Faleck, Ghassan K. Abou-Alfa, Kathleen C. Mcauliffe, Pamela Vaiskauskas, Mark L. Solter, Martinique Ogle, Matthew J. Adamow, Aliya Holland, Pallavi Vedantam, Phillip Wong, Taha Merghoub, Efsevia Vakiani, Travis J. Hollmann, Krishna Juluru, Joanne F. Chou, Marinela Capanu, Joseph Erinjeri, Stephen Solomon, Yoshiya Yamada, Nancy Kemeny, Christopher H. Crane, Leonard B. Saltz

Radiation treatment summary

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MSK Cancer Center

AstraZeneca

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ARTICLE ABSTRACT

Immune checkpoint inhibition (ICI) alone is not active in mismatch repair–proficient (MMR-P) metastatic colorectal cancer (mCRC), nor does radiotherapy alone result in objective systemic benefit. However, combined radiotherapy plus ICI can induce systemic antitumor immunity in preclinical and clinical models. In this single-center, phase II study, patients with chemotherapy-refractory MMR-P mCRC received durvalumab 1,500 mg plus tremelimumab 75 mg every 4 weeks plus radiotherapy. The primary endpoint was objective response rate (ORR) in nonirradiated lesions. Treatment and efficacy were correlated with peripheral immune cell profiles. We enrolled 24 patients, and report outcomes after a median follow-up of 21.8 (range: 15.9–26.3) months. The ORR was 8.3% (2 patients) [95% confidence interval (CI), 1.0–27.0]. The median progression-free survival was 1.8 (95% CI, 1.7–1.9) months, median overall survival was 11.4 (95% CI, 10.1–17.4) months. Twenty five percent of patients (n = 6) had treatment-related grade 3–4 adverse events. We observed increased circulating CD8+ T lymphocyte activation, differentiation, and proliferation in patients with objective response. This combination of radiotherapy plus ICI study did not meet the prespecified endpoint criteria to be considered worthwhile for further study. However, rare instances of systemic immune augmentation and regression in nonirradiated lesions were observed (an abscopal response). Combination durvalumab and tremelimumab plus radiotherapy is feasible in MMR-P mCRC with a manageable safety profile. Further studies of novel immunotherapy combinations, and identification of biomarkers predictive of abscopal response are warranted.

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    Clinical Cancer Research

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    cancer

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