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Attend this session at the
2019 ASCO Annual Meeting!


Session: Developmental Immunotherapy and Tumor Immunobiology

Type: Poster Session

Time: Saturday June 1, 8:00 AM to 11:00 AM

Location: Hall A

Molecular circulating tumor DNA response to identify long-term survival in patients receiving immunotherapy with initial radiologic stable disease.

Sub-category:
Circulating Biomarkers

Category:
Developmental Immunotherapy and Tumor Immunobiology

Meeting:
2019 ASCO Annual Meeting

Abstract No:
2546

Poster Board Number:
Poster Session (Board #190)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 2546)

Author(s): Matthew David Hellmann, Qu Zhang, Shaad Essa Abdullah, Jamie E. Chaft, Neil Howard Segal, Chen Gao, Phillip A. Dennis, Brandon W. Higgs; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; AstraZeneca, Gaithersburg, MD; MedImmune, Gaithersburg, MD

Abstract Disclosures

Abstract:

Background: Early on-treatment changes in ctDNA may identify responders to immunotherapy and complement radiologic assessment of benefit. Here we investigate how early changes in ctDNA associate with long-term survival following treatment with immunotherapy, and if differential patterns in molecular ctDNA response (MCR) among patients with radiologic stable disease (SD) at first on-treatment scan could identify patients deriving benefit from treatment. Methods: Paired pre- and on-treatment (week 6-8) plasma samples from 3 cohorts of patients treated with durvalumab (D) +/- tremelimumab (D+T) were evaluated (NCT01693562, NCT02087423, NCT02261220). CtDNA was profiled with the 73-gene Guardant 360 assay. Nonsynonymous variants were summarized per patient to calculate variant allelic frequency changes (dVAF) and on-treatment variant allele frequency (pVAF). A combination of dVAF and pVAF was used to define MCR. Results: The reduction of ctDNA (dVAF<0) and undetectable on-treatment ctDNA (pVAF=0) were each associated with improved OS and PFS. An optimal threshold for MCR was determined from one cohort, then applied to the other cohorts. MCR associated with significantly improved PFS and OS across all three cohorts (Table). MCR was then applied to a pooled subgroup of patients with initial radiologic SD from all three cohorts (n=78). Patients with radiologic SD and MCR were significantly more likely than those without MCR to achieve radiologic CR or PR (pooled Odds ratio 12.7, p<0.001), had improved PFS (stratified pooled HR 0.36, p<0.001), and improved OS (stratified pooled HR 0.38, p=0.005). Conclusions: MCR is an early on-treatment tool that may identify patients with improved long-term survival and patients with radiologic SD who derive clinical benefit from immunotherapy. MCR may be a supportive endpoint in prospective clinical trials. MCR and survival benefit.

StudyNCT01693562
D (n=72)
NCT02087423
D (n=71)
NCT02261220
D+T (n=36)
MCR, n (%)34 (47)28 (39)16 (44)
PFS HR (95% CI)0.28 (0.16,0.50)0.40 (0.22,0.73)0.12 (0.05,0.32)
OS HR (95% CI)0.25 (0.13,0.49)0.34 (0.14,0.83)*0.15 (0.05,0.44)

*<0.05, <0.01, <0.001

 
Other Abstracts in this Sub-Category:

 

1. Clonal expansion of tumor infiltrating lymphocytes (TILs) in the peripheral blood of metastatic melanoma patients is significantly associated with response to CTLA4 blockade-based immunotherapy.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2541 First Author: Arjun Khunger
Category: Developmental Immunotherapy and Tumor Immunobiology - Circulating Biomarkers

 

2. Bespoke circulating tumor DNA (ctDNA) analysis as a predictive biomarker in solid tumor patients (pts) treated with single-agent pembrolizumab (P).

Meeting: 2019 ASCO Annual Meeting Abstract No: 2542 First Author: Marco Adelmo James Iafolla
Category: Developmental Immunotherapy and Tumor Immunobiology - Circulating Biomarkers

 

3. Evolution of the myeloid-derived suppressor cells in advanced breast cancer and comparative analysis with a healthy population cohort.

Meeting: 2019 ASCO Annual Meeting Abstract No: 2543 First Author: Natalia Palazón-Carrión
Category: Developmental Immunotherapy and Tumor Immunobiology - Circulating Biomarkers

 

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