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Abstract B176: Sequential immunotherapy and association with clinical outcomes in advanced-stage cancer patients

Mehmet Bilen, Dylan Martini, Yuan Liu, Colleen Lewis, Hannah Collins, Julie Shabto, Mehmet Akce, Haydn Kissick, Bradley Carthon, Walid Shaib, Olatunji Alese, Rathi Pillai, Conor Steuer, Christina Wu, David Lawson, Ragini Kudchadkar, Bassel El-Rayes, Viraj Master, Suresh Ramalingam, Taofeek Owonikoko and R. Donald Harvey
Mehmet Bilen
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Dylan Martini
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Yuan Liu
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Colleen Lewis
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Hannah Collins
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Julie Shabto
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Mehmet Akce
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Haydn Kissick
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Bradley Carthon
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Walid Shaib
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Olatunji Alese
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Rathi Pillai
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Conor Steuer
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Christina Wu
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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David Lawson
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Ragini Kudchadkar
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Bassel El-Rayes
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Viraj Master
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Suresh Ramalingam
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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Taofeek Owonikoko
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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R. Donald Harvey
Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute of Emory University, Atlanta, GA.
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DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-B176 Published February 2019
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Abstracts: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30 - October 3, 2018; New York, NY

Abstract

Background: There are now six approved immune checkpoint inhibitors for several different malignancies including melanoma, head and neck cancer, lung cancer, and renal cell carcinoma. Given the increased number of available immunotherapeutic agents, more patients are presenting in clinic as candidates for sequential immunotherapy. However, the efficacy of sequential immunotherapy in a trial setting is unknown. We investigated the association between prior treatment with immune checkpoint inhibitors and clinical outcomes in patients treated with subsequent immunotherapy in a phase 1 clinical trial. Methods: We conducted a retrospective review of 90 advanced stage cancer patients treated on immunotherapy-based phase 1 clinical trials at Winship Cancer Institute between 2009 and 2017. We included 49 patients with an immune checkpoint-indicated histology (melanoma, lung cancer, head and neck cancer, and bladder cancer). Patients were then analyzed based on whether they had received at least one immune checkpoint inhibitor prior to enrollment. Overall survival (OS) and progression-free survival (PFS) were calculated in months from immunotherapy initiation on trial to date of death and clinical or radiographic progression, respectively. Clinical benefit (CB) was defined as a best response of complete response (CR), partial response (PR), or stable disease (SD). Univariate analysis (UVA) and multivariate analysis (MVA) were carried out using Cox proportional hazard or logistic regression model. Covariates included age, presence of liver metastases, number of prior lines of systemic therapy, histology, and Royal Marsden Hospital (RMH) risk group. Results: The median age was 67 years and most patients (78%) were men. The most common histologies were melanoma (61%) and lung/head and neck cancers (37%). The majority (81%) of patients were RMH good risk. More than half of patients (n=27, 55%) had received at least one immune checkpoint inhibitor prior to trial enrollment: ten received anti-PD-1, two received anti-CTLA-4, five received anti-PD-1/CTLA-4 combination therapy, and ten received multiple immune checkpoint inhibitors. In MVA, patients who had not received a prior immune checkpoint inhibitor had significantly longer OS (HR: 0.22, CI: 0.07-0.70, p=0.010). These patients also trended towards longer PFS (HR: 0.86, CI: 0.39-1.87, p=0.699) and higher chance of CB (HR: 2.52, CI: 0.49-12.97, p=0.268). Immunotherapy-naïve patients had substantially longer OS (24.3 vs 10.9 months) and PFS (5.1 vs. 2.8 months) than patients who had prior immunotherapy per Kaplan-Meier estimation. Conclusion: Optimal treatment options for oncology patients who progress on immune checkpoint inhibitors are lacking. In this study, patients who received at least one prior immune checkpoint inhibitor had worse clinical outcomes on immunotherapy-based phase 1 clinical trials than immune checkpoint-naïve patients. This suggests that further development of immunotherapy combination therapies is needed to improve clinical outcomes of these patients. The results from this study should be validated in a larger, prospective study.

Citation Format: Mehmet Bilen, Dylan Martini, Yuan Liu, Colleen Lewis, Hannah Collins, Julie Shabto, Mehmet Akce, Haydn Kissick, Bradley Carthon, Walid Shaib, Olatunji Alese, Rathi Pillai, Conor Steuer, Christina Wu, David Lawson, Ragini Kudchadkar, Bassel El-Rayes, Viraj Master, Suresh Ramalingam, Taofeek Owonikoko, R. Donald Harvey. Sequential immunotherapy and association with clinical outcomes in advanced-stage cancer patients [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B176.

  • ©2019 American Association for Cancer Research.
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Cancer Immunology Research: 7 (2 Supplement)
February 2019
Volume 7, Issue 2 Supplement
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Abstract B176: Sequential immunotherapy and association with clinical outcomes in advanced-stage cancer patients
Mehmet Bilen, Dylan Martini, Yuan Liu, Colleen Lewis, Hannah Collins, Julie Shabto, Mehmet Akce, Haydn Kissick, Bradley Carthon, Walid Shaib, Olatunji Alese, Rathi Pillai, Conor Steuer, Christina Wu, David Lawson, Ragini Kudchadkar, Bassel El-Rayes, Viraj Master, Suresh Ramalingam, Taofeek Owonikoko and R. Donald Harvey
Cancer Immunol Res February 1 2019 (7) (2 Supplement) B176; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-B176

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Abstract B176: Sequential immunotherapy and association with clinical outcomes in advanced-stage cancer patients
Mehmet Bilen, Dylan Martini, Yuan Liu, Colleen Lewis, Hannah Collins, Julie Shabto, Mehmet Akce, Haydn Kissick, Bradley Carthon, Walid Shaib, Olatunji Alese, Rathi Pillai, Conor Steuer, Christina Wu, David Lawson, Ragini Kudchadkar, Bassel El-Rayes, Viraj Master, Suresh Ramalingam, Taofeek Owonikoko and R. Donald Harvey
Cancer Immunol Res February 1 2019 (7) (2 Supplement) B176; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-B176
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