Dataset Information

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8⁺ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

ABSTRACT:

Purpose

In oropharyngeal squamous cell carcinoma (OPC), high CD8⁺ tumor-infiltrating lymphocyte (CD8⁺TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8⁺TIL 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 + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8⁺TIL 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 CD8⁺TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 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 CD8⁺TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8⁺TIL change in patients with a MPR was seen (P = 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 + tremelimumab did not increase CD8⁺TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.

SUBMITTER: Ferrarotto R

PROVIDER: S-EPMC8362306 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8<sup>+</sup> Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

Ferrarotto Renata R Bell Diana D Rubin Maria L ML Hutcheson Katherine A KA Johnson Jason M JM Goepfert Ryan P RP Phan Jack J Elamin Yasir Y YY Torman Danice K DK Warneke Carla L CL Hessel Amy C AC Garden Adam S AS Myers Jeffrey N JN Johnson Faye M FM Lee J Jack JJ Sikora Andrew G AG Gillison Maura L ML Glisson Bonnie S BS Gross Neil D ND

Clinical cancer research : an official journal of the American Association for Cancer Research 20200408 13

<h4>Purpose</h4>In oropharyngeal squamous cell carcinoma (OPC), high CD8<sup>+</sup> tumor-infiltrating lymphocyte (CD8<sup>+</sup>TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8<sup>+</sup>TIL density, safety, and efficacy in patients with OPC.<h4>Patients and methods</h4>Patients with newly diagnosed stage II-IVA OPC or locoregionally recurrent OPC amenable to resection wer ...[more]

PMID: 32269052

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Project description:ImportanceNew therapeutic options for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) are needed. This study evaluated dual checkpoint combination therapy in patients with mPDAC.ObjectiveTo evaluate the safety and efficacy of the anti-PD-L1 (programmed death-ligand 1) antibody using either durvalumab monotherapy or in combination with the anticytotoxic T-lymphocyte antigen 4 antibody using durvalumab plus tremelimumab therapy in patients with mPDAC.Design, setting, and participantsPart A of this multicenter, 2-part, phase 2 randomized clinical trial was a lead-in safety, open-label study with planned expansion to part B pending an efficacy signal from part A. Between November 26, 2015, and March 23, 2017, 65 patients with mPDAC who had previously received only 1 first-line fluorouracil-based or gemcitabine-based treatment were enrolled at 21 sites in 6 countries. Efficacy analysis included the intent-to-treat population; safety analysis included patients who received at least 1 dose of study treatment and for whom any postdose data were available.InterventionsPatients received durvalumab (1500 mg every 4 weeks) plus tremelimumab (75 mg every 4 weeks) combination therapy for 4 cycles followed by durvalumab therapy (1500 mg every 4 weeks) or durvalumab monotherapy (1500 mg every 4 weeks) for up to 12 months or until the onset of progressive disease or unacceptable toxic effects.Main outcomes and measuresSafety and efficacy were measured by objective response rate, which was used to determine study expansion to part B. The threshold for expansion was an objective response rate of 10% for either treatment arm.ResultsAmong 65 randomized patients, 34 (52%) were men and median age was 61 (95% CI, 37-81) years. Grade 3 or higher treatment-related adverse events occurred in 7 of 32 patients (22%) receiving combination therapy and in 2 of 32 patients (6%) receiving monotherapy; 1 patient randomized to the monotherapy arm did not receive treatment owing to worsened disease. Fatigue, diarrhea, and pruritus were the most common adverse events in both arms. Overall, 4 of 64 patients (6%) discontinued treatment owing to treatment-related adverse events. Objective response rate was 3.1% (95% CI, 0.08-16.22) for patients receiving combination therapy and 0% (95% CI, 0.00-10.58) for patients receiving monotherapy. Low patient numbers limited observation of the associations between treatment response and PD-L1 expression or microsatellite instability status.Conclusion and relevanceTreatment was well tolerated, and the efficacy of durvalumab plus tremelimumab therapy and durvalumab monotherapy reflected a population of patients with mPDAC who had poor prognoses and rapidly progressing disease. Patients were not enrolled in part B because the threshold for efficacy was not met in part A.Trial registrationClinicalTrials.gov identifier: NCT02558894.

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Dataset Information

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8⁺ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

Purpose

Patients and methods

Results

Conclusions

Publications

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8<sup>+</sup> Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

Purpose

Patients and methods

Results

Conclusions

Publications

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8<sup>+</sup> Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8⁺ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.