Impact of neoadjuvant durvalumab with or without tremelimumab on CD8+ tumor lymphocyte density, safety, and efficacy in patients with oropharynx cancer: CIAO trial results

Renata Ferrarotto, Diana Bell, Maria L. Rubin, Katherine A. Hutcheson, Jason M. Johnson, Ryan P. Goepfert, Jack Phan, Yasir Y. Elamin, Danice K. Torman, Carla L. Warneke, Amy C. Hessel, Adam S. Garden, Jeffrey N. Myers, Faye M. Johnson, J. Jack Lee, Andrew G. Sikora, Maura L. Gillison, Bonnie S. Glisson, Neil D. Gross

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Purpose: In oropharyngeal squamous cell carcinoma (OPC), high CD8þ tumor-infiltrating lymphocyte (CD8þTIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab þ tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8þTIL density, safety, and efficacy in patients with OPC. Patients and Methods: Patients with newly diagnosed stage II-IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab þ tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8þTIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes. Results: Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8þTIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P ¼ 0.97; 95% CI: -1.07-2.28). In each group, 6 patients (43%, 95% CI: 17.66-71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8þTIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8þTIL change in patients with a MPR was seen (P ¼ 0.059; 95% CI: -0.33-3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence. Conclusions: Durvalumab þ tremelimumab did not increase CD8þTIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.

Original languageEnglish
Pages (from-to)3211-3219
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number13
DOIs
StatePublished - Jul 2020
Externally publishedYes

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